|
1
|
Toumi HR, Sallabi SM, Lubbad L, Al-Salam S, Hammad FT. The Effect of Nerolidol on Renal Dysfunction following Bilateral Ureteral Obstruction. Biomedicines 2024; 12:2285. [PMID: 39457599 PMCID: PMC11505435 DOI: 10.3390/biomedicines12102285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 10/02/2024] [Accepted: 10/04/2024] [Indexed: 10/28/2024] Open
Abstract
Background/Objectives: Obstructive uropathy is a common cause of renal impairment. Recently, there has been a burgeoning interest in exploring natural products as potential alternative remedies for many conditions due to their low toxicity, affordability and wide availability. Methods: We investigated the effect of nerolidol in a rat model of bilateral ureteral obstruction (BUO) injury. Nerolidol, dissolved in a vehicle, was administered orally as a single daily dose of 200 mg/kg to Wistar rats. Sham group (n = 12) underwent sham surgery, whereas the BUO (n = 12) and BUO/NR groups (n = 12) underwent reversible 24-h BUO and received the vehicle or nerolidol, respectively. The treatment started 9 days prior to the BUO/sham surgery and continued for 3 days after reversal. Renal functions were assessed before starting the treatment, just prior to the intervention and 3 days after BUO reversal. Results: Neither nerolidol nor the vehicle affected the basal renal functions. Nerolidol resulted in a significant attenuation in the BUO-induced alterations in renal functional parameters such as serum creatinine and urea, creatinine clearance and urinary albumin-creatinine ratio. Nerolidol also attenuated the changes in several markers associated with renal injury, inflammation, apoptosis and oxidative stress and mitigated the histological alterations. Conclusions: The findings of this study demonstrated the potent reno-protective effects of nerolidol in mitigating the adverse renal effects of bilateral ureteral obstruction. This is attributed to its anti-inflammatory, anti-fibrotic, anti-apoptotic and anti-oxidant properties. These effects were reflected in the partial recovery of renal functions and histological features. These findings may have potential therapeutic implications.
Collapse
Affiliation(s)
- Harun R. Toumi
- Department of Surgery, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates; (H.R.T.); (S.M.S.); (L.L.)
| | - Sundus M. Sallabi
- Department of Surgery, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates; (H.R.T.); (S.M.S.); (L.L.)
| | - Loay Lubbad
- Department of Surgery, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates; (H.R.T.); (S.M.S.); (L.L.)
| | - Suhail Al-Salam
- Department of Pathology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates;
| | - Fayez T. Hammad
- Department of Surgery, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain P.O. Box 17666, United Arab Emirates; (H.R.T.); (S.M.S.); (L.L.)
| |
Collapse
|
|
2
|
Liso A, Venuto S, Coda ARD, Giallongo C, Palumbo GA, Tibullo D. IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis. Int J Mol Sci 2022; 23:ijms23084358. [PMID: 35457175 PMCID: PMC9030159 DOI: 10.3390/ijms23084358] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/04/2022] [Accepted: 04/12/2022] [Indexed: 12/12/2022] Open
Abstract
Insulin-like growth factors binding protein-6 (IGFBP-6) is involved in a relevant number of cellular activities and represents an important factor in the immune response, particularly in human dendritic cells (DCs). Over the past several years, significant insights into the IGF-independent effects of IGFBP-6 were discovered, such as the induction of chemotaxis, capacity to increase oxidative burst and neutrophils degranulation, ability to induce metabolic changes in DCs, and, more recently, the regulation of the Sonic Hedgehog (SHH) signaling pathway during fibrosis. IGFBP-6 has been implicated in different human diseases, and it plays a rather controversial role in the biology of tumors. Notably, well established relationships between immunity, stroma activity, and fibrosis are prognostic and predictive of response to cancer immunotherapy. This review aims at describing the current understanding of mechanisms that link IGFBP-6 and fibrosis development and at highlighting the multiple roles of IGFBP-6 to provide an insight into evolutionarily conserved mechanisms that can be relevant for inflammation, tumor immunity, and immunological diseases.
Collapse
Affiliation(s)
- Arcangelo Liso
- Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (S.V.); (A.R.D.C.)
- Correspondence:
| | - Santina Venuto
- Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (S.V.); (A.R.D.C.)
| | - Anna Rita Daniela Coda
- Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (S.V.); (A.R.D.C.)
| | - Cesarina Giallongo
- Department of Medical Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy; (C.G.); (G.A.P.)
| | - Giuseppe Alberto Palumbo
- Department of Medical Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy; (C.G.); (G.A.P.)
| | - Daniele Tibullo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy;
| |
Collapse
|
|
3
|
Jang SJ, Choi BS, Choi SH. Evaluation of Renal Function in Obstructed Ureter Model Using 99mTc-DMSA. In Vivo 2021; 34:2431-2435. [PMID: 32871769 DOI: 10.21873/invivo.12057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 06/30/2020] [Accepted: 07/01/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM Urinary obstruction is a condition of impaired urinary drainage, which may result in progressive renal deterioration. This study applied 99mTc-labeled dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy to a rabbit model of right ureter obstruction and evaluated its utility in studying obstructive renal diseases. MATERIALS AND METHODS Complete unilateral ureter obstruction in rabbits was generated by complete ligation of the right ureter. Renal function was investigated during a 4-week post-obstruction period by obtaining planar images of 99mTc-DMSA activity following ear vein injection. Renal blood perfusion was evaluated by non-invasive scintigraphy in conjunction with parallel histological and hematological examinations. RESULTS Renal perfusion was remarkably and rapidly reduced in the ureter-obstructed kidneys. During the experimental period, the size of left kidney appeared normal in the scintigraphic images, but the ureter-obstructed right kidney progressively became larger. Histopathological examination showed flattening and atrophy of tubules, enlargement of interstitial areas, accumulation of extracellular martices and infiltration of inflammatory cells in the obstreucted kidney. CONCLUSION 99mTc-DMSA scintigraphy is a sensitive, non-invasive method to assess renal function in unilateral kidney diseases.
Collapse
Affiliation(s)
- Seok Jin Jang
- Onnuri Animal Medical Center, Cheongju, Republic of Korea
| | - Byung Soo Choi
- College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Seok Hwa Choi
- College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| |
Collapse
|
|
4
|
Sombié HK, Sorgho AP, Kologo JK, Ouattara AK, Yaméogo S, Yonli AT, Djigma FW, Tchelougou D, Somda D, Kiendrébéogo IT, Bado P, Nagalo BM, Nagabila Y, Adoko ETHD, Zabsonré P, Millogo H, Simporé J. Glutathione S-transferase M1 and T1 genes deletion polymorphisms and risk of developing essential hypertension: a case-control study in Burkina Faso population (West Africa). BMC MEDICAL GENETICS 2020; 21:55. [PMID: 32188413 PMCID: PMC7081581 DOI: 10.1186/s12881-020-0990-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 03/02/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Glutathione S-transferases play a key role in the detoxification of persistent oxidative stress products which are one of several risks factors that may be associated with many types of disease processes such as cancer, diabetes, and hypertension. In the present study, we characterize the null genotypes of GSTM1 and GSTT1 in order to investigate the association between them and the risk of developing essential hypertension. METHODS We conducted a case-control study in Burkina Faso, including 245 subjects with essential hypertension as case and 269 control subjects with normal blood pressure. Presence of the GSTT1 and GSTM1 was determined using conventional multiplex polymerase chain reaction followed by gel electrophoresis analysis. Biochemical parameters were measured using chemistry analyzer CYANExpert 130. RESULTS Chi-squared test shows that GSTT1-null (OR = 1.82; p = 0.001) and GSTM1-active/GSTT1-null genotypes (OR = 2.33; p < 0.001) were significantly higher in cases than controls; the differences were not significant for GSTM1-null, GSTM1-null/GSTT1-active and GSTM1-null/GSTT1-null (p > 0.05). Multinomial logistic regression revealed that age ≥ 50 years, central obesity, family history of hypertension, obesity, alcohol intake and GSTT1 deletion were in decreasing order independent risk factors for essential hypertension. Analysis by gender, BMI and alcohol showed that association of GSTT1-null with risk of essential hypertension seems to be significant when BMI < 30 Kg/m2, in non-smokers and in alcohol users (all OR ≥ 1.77; p ≤ 0.008). Concerning GSTT1, GSTM1 and cardiovascular risk markers levels in hypertensive group, we found that subjects with GSTT1-null genotype had higher waist circumference and higher HDL cholesterol level than those with GSTT1-active (all p < 0.005), subjects with GSTM1-null genotype had lower triglyceride than those with GSTM1-active (p = 0.02) and subjects with the double deletion GSTM1-null/GSTT1-null had higher body mass index, higher waist circumference and higher HDL cholesterol than those with GSTM1-active/GSTT1-active genotype (all p = 0.01). CONCLUSION Our results confirm that GSTT1-null genotype is significantly associated with risk of developing essential hypertension in Burkinabe, especially when BMI < 30 Kg/m2, in non-smokers and in alcohol users, and it showed that the double deletion GSTM1-null/GSTT1-null genotypes may influence body lipids repartition.
Collapse
Affiliation(s)
- Herman Karim Sombié
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso
| | - Abel Pegdwendé Sorgho
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso
| | - Jonas Koudougou Kologo
- Saint Camille Hospital of Ouagadougou (HOSCO), 01 P.O. Box 444, Ouagadougou 01, Burkina Faso.,University Hospital Center-Yalgado Ouédraogo (CHUYO), 01 P.O. Box 676, Ouagadougou, Burkina Faso
| | - Abdoul Karim Ouattara
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso. .,Pietro Annigoni Biomolecular Research Center (CERBA), P.O. Box 364, Ouagadougou 01, Burkina Faso.
| | - Sakinata Yaméogo
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso
| | - Albert Théophane Yonli
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso.,Pietro Annigoni Biomolecular Research Center (CERBA), P.O. Box 364, Ouagadougou 01, Burkina Faso
| | - Florencia Wendkuuni Djigma
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso.,Pietro Annigoni Biomolecular Research Center (CERBA), P.O. Box 364, Ouagadougou 01, Burkina Faso
| | - Daméhan Tchelougou
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso
| | - Dogfounianalo Somda
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso
| | | | - Prosper Bado
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso
| | - Bolni Marius Nagalo
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso
| | - Youssoufou Nagabila
- Saint Camille Hospital of Ouagadougou (HOSCO), 01 P.O. Box 444, Ouagadougou 01, Burkina Faso
| | | | - Patrice Zabsonré
- University Hospital Center-Yalgado Ouédraogo (CHUYO), 01 P.O. Box 676, Ouagadougou, Burkina Faso
| | - Hassanata Millogo
- Pietro Annigoni Biomolecular Research Center (CERBA), P.O. Box 364, Ouagadougou 01, Burkina Faso
| | - Jacques Simporé
- Laboratory of Molecular Biology and Genetics (LABIOGENE), UFR/SVT, University Joseph Ki-Zerbo, 03 P.O. Box 7021, Ouagadougou 03, Burkina Faso.,Saint Camille Hospital of Ouagadougou (HOSCO), 01 P.O. Box 444, Ouagadougou 01, Burkina Faso.,Pietro Annigoni Biomolecular Research Center (CERBA), P.O. Box 364, Ouagadougou 01, Burkina Faso.,Faculty of Medicine, University Saint Thomas d'Aquin, P.O. Box 10212, Ouagadougou, Burkina Faso
| |
Collapse
|
|
5
|
Kaeidi A, Sahamsizadeh A, Allahtavakoli M, Fatemi I, Rahmani M, Hakimizadeh E, Hassanshahi J. The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis. Mol Biol Rep 2019; 47:1371-1379. [PMID: 31873871 DOI: 10.1007/s11033-019-05237-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 12/10/2019] [Indexed: 12/19/2022]
Abstract
Unilateral ureteral obstruction (UUO) induces kidney injury. Oleuropein as a major compound of olive leaves modulates the inflammatory parameters and decreases oxidative stress. Accordingly, we evaluate the renoprotective effect of oleuropein against 3-day UUO rats. Forty rats were randomly divided into five groups (n = 8) including control, UUO and UUO + oleuropein groups (50, 100 and 200 mg/kg). UUO model was induced by left ureter ligation and continued for 3-day. Rats were treated synchronic daily for 3-day, then mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), serum creatinine level, and also superoxide dismutase (SOD), glutathione peroxidase (GPx) activity levels and malondialdehyde (MDA) concentration (in the obstructed kidney) were measured. The western blotting method was applied to evaluate the Bax, Bcl-2, cleaved caspase-3 and TNF-α proteins expression level. The hematoxylin and eosin method was applied to evaluate the kidney tissue damage score (KTDS). UUO significantly increased RVR, KTDS, and MDA, cleaved caspase-3, Bax, serum creatinine and TNF-α protein levels (P < 0.05), and also significantly decreased RBF, SOD, and GPx and Bcl-2 protein expression levels (P < 0.001) in the obstructed kidney and oleuropein (200 mg/kg) significantly ameliorated the changes induced by UUO. Our findings showed that oleuropein has a renoprotective effect against 3-day UUO. The mechanisms underlying the observed effects may be related to its antioxidative stress, anti-apoptotic, and anti-inflammatory effects.
Collapse
Affiliation(s)
- Ayat Kaeidi
- Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, P.O. Box:77175-835, 7719617996, Rafsanjan, Iran
| | - Ali Sahamsizadeh
- Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, P.O. Box:77175-835, 7719617996, Rafsanjan, Iran
| | - Mohammad Allahtavakoli
- Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, P.O. Box:77175-835, 7719617996, Rafsanjan, Iran
| | - Iman Fatemi
- Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, P.O. Box:77175-835, 7719617996, Rafsanjan, Iran
| | - Mohammadreza Rahmani
- Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Elham Hakimizadeh
- Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Jalal Hassanshahi
- Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, P.O. Box:77175-835, 7719617996, Rafsanjan, Iran.
| |
Collapse
|
|
6
|
Perretta‐Tejedor N, Muñoz‐Félix JM, Düwel A, Quiros‐Luis Y, Fernández‐Martín JL, Morales AI, López‐Hernández FJ, López‐Novoa JM, Martínez‐Salgado C. Cardiotrophin-1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease. Acta Physiol (Oxf) 2019; 226:e13247. [PMID: 30589223 DOI: 10.1111/apha.13247] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 12/17/2018] [Accepted: 12/21/2018] [Indexed: 12/12/2022]
Abstract
AIM Chronic kidney disease is characterized by tubulointerstitial fibrosis involving inflammation, tubular apoptosis, fibroblast proliferation and extracellular matrix accumulation. Cardiotrophin-1, a member of the interleukin-6 family of cytokines, protects several organs from damage by promoting survival and anti-inflammatory effects. However, whether cardiotrophin-1 participates in the response to chronic kidney injury leading to renal fibrosis is unknown. METHODS We hypothesized and assessed the potential role of cardiotrophin-1 in a mice model of tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). RESULTS Three days after UUO, obstructed kidneys from cardiotrophin-1-/- mice show higher expression of inflammatory markers IL-1β, Cd68, ICAM-1, COX-2 and iNOs, higher activation of NF-κB, higher amount of myofibroblasts and higher severity of tubular damage and apoptosis, compared with obstructed kidneys from wild-type littermates. In a later stage, obstructed kidneys from cardiotrophin-1-/- mice show higher fibrosis than obstructed kidneys from wild-type mice. Interestingly, administration of exogenous cardiotrophin-1 prevents the increased fibrosis resulting from the genetic knockout of cardiotrophin-1 upon UUO, and supplementation of wild-type mice with exogenous cardiotrophin-1 further reduces the renal fibrosis induced by UUO. In vitro, renal myofibroblasts from cardiotrophin-1-/- mice have higher collagen I and fibronectin expression and higher NF-κB activation than wild-type cells. CONCLUSIONS Cardiotrophin-1 participates in the endogenous response that opposes renal damage by counteracting the inflammatory, apoptotic and fibrotic processes. And exogenous cardiotrophin-1 is proposed as a candidate for the treatment and prevention of chronic renal fibrosis.
Collapse
Affiliation(s)
- Nuria Perretta‐Tejedor
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
- Institute of Health Sciences Studies of Castilla y Leon (IECSCYL) Salamanca Spain
- Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain
| | - José M. Muñoz‐Félix
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
- Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain
| | - Annette Düwel
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
- Institute of Health Sciences Studies of Castilla y Leon (IECSCYL) Salamanca Spain
- Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain
| | - Yaremi Quiros‐Luis
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
| | - José L. Fernández‐Martín
- UGC Bone Metabolism Institute of Health Research of the Principality of Asturias (ISPA) Oviedo Asturias Spain
| | - Ana I. Morales
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
- Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain
| | - Francisco J. López‐Hernández
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
- Institute of Health Sciences Studies of Castilla y Leon (IECSCYL) Salamanca Spain
- Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain
| | - José M. López‐Novoa
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
- Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain
| | - Carlos Martínez‐Salgado
- Department of Physiology and Pharmacology, Translational Research on Renal and Cardiovascular Diseases (TRECARD) University of Salamanca Salamanca Spain
- Institute of Health Sciences Studies of Castilla y Leon (IECSCYL) Salamanca Spain
- Institute of Biomedical Research of Salamanca (IBSAL) Salamanca Spain
| |
Collapse
|
|
7
|
Li J, Sun M, Ye J, Li Y, Jin R, Zheng H, Liang F. The Mechanism of Acupuncture in Treating Essential Hypertension: A Narrative Review. Int J Hypertens 2019; 2019:8676490. [PMID: 30984420 PMCID: PMC6431462 DOI: 10.1155/2019/8676490] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 02/14/2019] [Indexed: 01/13/2023] Open
Abstract
Essential hypertension has a high incidence worldwide, and patients with essential hypertension endure a lifetime of medication, leading to a heavy economic burden on the patient's family and causing serious impacts on the patient's quality of life. Much evidence has demonstrated that acupuncture as an adjunctive therapy can lower blood pressure in patients with hypertension, but the mechanism of its action is unclear. This article reviews the research from 2000 to 2018 regarding the mechanism of acupuncture for hypertension, and we summarize the current knowledge about using acupuncture for hypertension. We found that the mechanism whereby acupuncture lowers blood pressure is related to the regulation of renin-angiotensin-aldosterone system, vascular endothelium, oxidative stress, neuroendocrine system, and so on. Besides, there may be cross-talk between multiple systems and multiple targets. We also investigate the influence factors of acupuncture for hypertension. These results may provide evidence and research ideas for the treatment of hypertension via acupuncture.
Collapse
Affiliation(s)
- Juan Li
- College of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Mingsheng Sun
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Jing Ye
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Yuxi Li
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Rongjiang Jin
- College of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Hui Zheng
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Fanrong Liang
- College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| |
Collapse
|
|
8
|
Hammad FT, Salam SA, Nemmar A, Ali M, Lubbad L. The Effect of Arabic Gum on Renal Function in Reversible Unilateral Ureteric Obstruction. Biomolecules 2019; 9:biom9010025. [PMID: 30641998 PMCID: PMC6359443 DOI: 10.3390/biom9010025] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 01/07/2019] [Accepted: 01/08/2019] [Indexed: 02/07/2023] Open
Abstract
Arabic gum (AG) has antioxidant and anti-inflammatory properties. However, the effect of AG in ureteric obstruction (UO) has not been investigated yet. Male rats underwent reversible left unilateral UO (UUO) for 72 h. Group AG-1 (n = 12) received AG 15 g/kg/day dissolved in drinking water starting seven days before and continuing throughout the period of the UUO, whereas group Vx-1 (n = 8) had only water. Group AG-2 (n = 12) and Vx-2 (n = 8) had similar protocols as AG-1 and Vx-1, respectively, but underwent terminal experiments to measure renal functions, six days post-UUO reversal. Arabic gum significantly attenuated the UUO-induced increase in the tissue level of malonedialdehyde and superoxide dismutase and the rise in the gene expression of TNF-α, TGF-β1, and p53 in AG-1 compared to Vx-1. It also attenuated the severity of tubular dilatation. However, AG did not affect the alterations in the renal blood flow or glomerular filtration rate. The fractional sodium excretion was lower in AG-2 but did not reach statistical significance (0.40 ± 0.11 vs 0.74 ± 0.12, p = 0.07). AG attenuated the UUO-induced rise in oxidative stress markers and proinflammatory and profibrotic cytokines and the degree of renal tubular dilatation, indicating a protective effect in obstructive nephropathy.
Collapse
Affiliation(s)
- Fayez T Hammad
- Department of Surgery, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain 17666, UAE.
| | - Suhail Al Salam
- Department of Pathology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain 17666, UAE.
| | - Abderrahim Nemmar
- Department of Physiology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain 17666, UAE.
| | - Mahmoud Ali
- Department of Pharmacology, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain 17666, UAE.
| | - Loay Lubbad
- Department of Surgery, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain 17666, UAE.
| |
Collapse
|
|
9
|
Shi B, Li S, Ju H, Liu X, Li D, Li Y. Protein kinase C inhibitor chelerythrine attenuates partial unilateral ureteral obstruction induced kidney injury in neonatal rats. Life Sci 2018; 216:85-91. [PMID: 30439378 DOI: 10.1016/j.lfs.2018.11.025] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 11/09/2018] [Accepted: 11/11/2018] [Indexed: 02/06/2023]
Abstract
The present study aimed to evaluate the renoprotective effects of chelerythrine (CHE), a protein kinase C inhibitor, on neonatal rats after partial unilateral ureteral obstruction (UUO) surgery. New born Sprague Dawley rats were subjected to partial UUO 48 h after birth and received a daily intraperitoneal injection of 5 mg/kg CHE. At 21-day age, the rats were scarified and the kidneys were collected for analysis. Results showed that CHE treatment significantly increased kidney weight and restored renal function in the obstructed kidney. Histological examination demonstrated that CHE attenuated renal injury by reducing renal parenchymal loss and preventing glomerular and tubular degeneration. In addition, CHE inhibited partial UUO-induced upregulated kidney injury molecule-1 expression and apoptosis and renal fibrosis. Moreover, as a PKC inhibitor, CHE significantly inhibited PKCα and PKCβ membrane translocation. This action may be associated with its effects of anti-apoptosis and anti-fibrosis and contribute to the renoprotection. This short-term study suggests that CHE is beneficial for obstructive nephropathy in neonatal rats and provides foundation for further studies to reveal the long-term effects of CHE on obstructive nephropathy in children and infants.
Collapse
Affiliation(s)
- Bo Shi
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Shixing Li
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Hao Ju
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Xin Liu
- Department of Paediatric Urology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Dan Li
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China
| | - Ying Li
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
| |
Collapse
|
|
10
|
Uric acid stones increase the risk of chronic kidney disease. Urolithiasis 2018; 46:543-547. [PMID: 29492591 DOI: 10.1007/s00240-018-1050-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Accepted: 02/22/2018] [Indexed: 02/07/2023]
Abstract
The aim of this study was to compare the clinical characteristics of uric acid stones and their potential risk for chronic kidney disease (CKD). A total of 401 patients (196 with uric acid stone and 205 without) were enrolled from our database of patients with urolithiasis. We analyzed the clinical demographic features, stone location, urine chemistries, and renal function. There was a significant difference (p < 0.001) between the two groups in terms of age, with the higher mean age in the uric acid group. Patients with uric acid stones had much lower pH of urine (p < 0.001) and higher serum uric acid level (p = 0.002). Notably, those with uric acid stones had worse eGFR than those with non-uric acid stones. Multivariate analysis confirmed that age over 60 years (ORs = 9.19; 95% CI 3.5-24.3), female sex (ORs = 4.01; 95% CI 1.8-9.0), hyperuricemia (ORs = 8.47; 95% CI 1.6-43.5), and uric acid stone (OR = 2.86; 95% CI 1.2-6.7) were the independent predictors of poor prognoses in CKD. Therefore, an association exists between uric acid stones and higher prevalence of CKD. Patients with uric acid stones may need close monitoring of renal function during follow-up.
Collapse
|
|
11
|
Cisek LJ. Holding Water: Congenital Anomalies of the Kidney and Urinary Tract, CKD, and the Ongoing Role of Excellence in Plumbing. Adv Chronic Kidney Dis 2017; 24:357-363. [PMID: 29229166 DOI: 10.1053/j.ackd.2017.09.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Congenital anomalies of the kidneys and urinary tracts can result in diminished natal kidney function, possibly through common embryologic pathway disruption or as a result of development taking place in the face of disordered 'post-renal' drainage. Impaired conduit and reservoir function present potential for an ongoing assault leading to further deterioration and progression of chronic kidney disease, a risk that extends to adults with these conditions, even after "correction". The drainage and storage aspects of the urinary system that can impact kidney function are reviewed with attention to correctable or manageable problems including: Bladder dysfunction wherein the low pressure storage of urine is compromised requiring the kidney to work against a pressure gradient, the classic post renal failure problem. The kidney in the aftermath of obstruction which may have lost concentrating capacity leading to a tendency to dehydration ('pre-renal' failure) and through polyuria which exacerbates bladder pressure problems. Further there is an added challenge in evaluation for ongoing or reemergent obstruction in a significantly dilated system where the capacious system leads to slow turnover of urine often requiring a ureteral stent or nephrostomy to clearly establish clinical significance of delayed drainage. Stasis where slow urine flow leads to buildup of debris (stone) or potentiates infection. Vessicoureteral reflux which allows for introduction of lower urinary tract bacteria to the kidney and can lead to pyelonephritis. Conditions which combine problems such as posterior urethral valves where the bladder outlet obstruction compromises kidney function potentially impairing concentrating ability, creates bladder compromise often reducing emptying efficiency or elevating bladder storage pressures, as well as dilating the system potentially promoting stasis. Cognizance of the potential for plumbing problems to further kidney deterioration as patients with congenital urinary tract anomalies, even after they have been repaired is incumbent on those caring for these patients as they age. Thoughtful evaluation of those patients in whom kidney compromise maybe aggravated by drainage and storage disorder will optimize native renal function.
Collapse
|
|
12
|
Kazama I, Nakajima T. Postrenal acute kidney injury in a patient with unilateral ureteral obstruction caused by urolithiasis: A case report. Medicine (Baltimore) 2017; 96:e8381. [PMID: 29069033 PMCID: PMC5671866 DOI: 10.1097/md.0000000000008381] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
RATIONALE In patients with bilateral ureteral obstruction, the serum creatinine levels are often elevated, sometimes causing postrenal acute kidney injury (AKI). In contrast, those with unilateral ureteral obstruction present normal serum creatinine levels, as long as their contralateral kidneys are preserved intact. However, the unilateral obstruction of the ureter could affect the renal function, as it humorally influences the renal hemodynamics. PATIENT CONCERNS A 66-year-old man with a past medical history of hypertension and diabetes mellitus came to our outpatient clinic because of right abdominal dullness. DIAGNOSES Unilateral ureteral obstruction caused by a radio-opaque calculus in the right upper ureter and a secondary renal dysfunction. INTERVENTIONS As oral hydration and the use of calcium antagonists failed to allow the spontaneous stone passage, extracorporeal shock wave lithotripsy (ESWL) was performed. OUTCOMES Immediately after the passage of the stone, the number of red blood cells in the urine was dramatically decreased and the serum creatinine level almost returned to the normal range with the significant increase in glomerular filtration rate. LESSONS Unilateral ureteral obstruction by the calculus, which caused reflex vascular constriction and ureteral spasm in the contralateral kidney, was thought to be responsible for the deteriorating renal function.
Collapse
Affiliation(s)
- Itsuro Kazama
- Department of Physiology, Tohoku University Graduate School of Medicine, Seiryo-cho, Aoba-ku
| | | |
Collapse
|
|
13
|
Sharma A, Sodhi KS, Saxena AK, Bhatia A, Menon P, Rao KLN, Khandelwal N. Comparison of intravenous urography and magnetic resonance urography in preoperative evaluation of pelvi-ureteric junction obstruction in children. J Indian Assoc Pediatr Surg 2016; 21:169-174. [PMID: 27695208 PMCID: PMC4980877 DOI: 10.4103/0971-9261.186546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Aims: To compare intravenous urography (IVU) and magnetic resonance urography (MRU) in the preoperative evaluation of pelvi-ureteric junction obstruction (PUJO) in children. Materials and Methods: A total of 35 children up to 10 years of age in whom unilateral or bilateral PUJO were suspected on ultrasonography were enrolled in this prospective study. All children underwent IVU and MRU, and the findings were compared. Results: Of the 70 kidneys evaluated, 14 (20%) were not visualized on IVU because of nonexcretion of contrast, whereas all the 70 (100%) kidneys were visualized on MRU. On IVU, nephrogram was not visualized in 66 (94.2%) of the 70 kidneys, whereas MRU showed prompt and homogeneous nephrogram in 68 (97.1%) of the 70 kidneys. No evidence of PUJO was seen in 31 (44.2%) kidneys on both IVU and MRU. IVU showed PUJO in 26 (37.1%) kidneys, whereas MRU showed it in 38 (54.2%) kidneys. MRU detected two duplex systems that were missed on IVU. A focal renal lesion and two incidental extra renal abnormalities were detected on MRU, which were not visualized on IVU. Conclusion: MRU is better than IVU, especially in case of poorly functioning kidneys which are not visualized on IVU. MRU also provides anatomic details of the ureter and vessels with better evaluation of renal parenchyma. It also has an additional advantage of detecting incidental extra renal abnormalities, if present.
Collapse
Affiliation(s)
- Alok Sharma
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Kushaljit Singh Sodhi
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Akshay Kumar Saxena
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anmol Bhatia
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Prema Menon
- Department of Pediatric Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Katragadda L N Rao
- Department of Pediatric Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Niranjan Khandelwal
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| |
Collapse
|
|
14
|
Islam MA, Kim S, Firdous J, Lee AY, Hong SH, Seo MK, Park TE, Yun CH, Choi YJ, Chae C, Cho CS, Cho MH. A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats. Biomaterials 2016; 102:43-57. [DOI: 10.1016/j.biomaterials.2016.06.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Revised: 06/02/2016] [Accepted: 06/05/2016] [Indexed: 02/07/2023]
|
|
15
|
Falke LL, Kinashi H, Dendooven A, Broekhuizen R, Stoop R, Joles JA, Nguyen TQ, Goldschmeding R. Age-dependent shifts in renal response to injury relate to altered BMP6/CTGF expression and signaling. Am J Physiol Renal Physiol 2016; 311:F926-F934. [PMID: 27558559 DOI: 10.1152/ajprenal.00324.2016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 08/17/2016] [Indexed: 02/07/2023] Open
Abstract
Age is associated with an increased prevalence of chronic kidney disease (CKD), which, through progressive tissue damage and fibrosis, ultimately leads to loss of kidney function. Although much effort is put into studying CKD development experimentally, age has rarely been taken into account. Therefore, we investigated the effect of age on the development of renal tissue damage and fibrosis in a mouse model of obstructive nephropathy (i.e., unilateral ureter obstruction; UUO). We observed that after 14 days, obstructed kidneys of old mice had more tubulointerstitial atrophic damage but less fibrosis than those of young mice. This was associated with reduced connective tissue growth factor (CTGF), and higher bone morphogenetic protein 6 (BMP6) expression and pSMAD1/5/8 signaling, while transforming growth factor-β expression and transcriptional activity were no different in obstructed kidneys of old and young mice. In vitro, CTGF bound to and inhibited BMP6 activity. In summary, our data suggest that in obstructive nephropathy atrophy increases and fibrosis decreases with age and that this relates to increased BMP signaling, most likely due to higher BMP6 and lower CTGF expression.
Collapse
Affiliation(s)
- Lucas L Falke
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Hiroshi Kinashi
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Nephrology and Renal Replacement Therapy, Nagoya University, Nagoya, Japan
| | - Amelie Dendooven
- Department of Pathology, University Medical Center, Antwerp, Belgium
| | - Roel Broekhuizen
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Reinout Stoop
- Department of Metabolic Health Research, TNO, Leiden, The Netherlands; and
| | - Jaap A Joles
- Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Tri Q Nguyen
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Roel Goldschmeding
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands;
| |
Collapse
|
|
16
|
Dursun M, Otunctemur A, Ozbek E, Sahin S, Besiroglu H, Ozsoy OD, Cekmen M, Somay A, Ozbay N. Protective effect of hydrogen sulfide on renal injury in the experimental unilateral ureteral obstruction. Int Braz J Urol 2016; 41:1185-93. [PMID: 26742979 PMCID: PMC4756947 DOI: 10.1590/s1677-5538.ibju.2014.0090] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Accepted: 05/13/2014] [Indexed: 02/07/2023] Open
Abstract
Introduction/Objective: Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats. Materials and Methods: 24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56μmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results: There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p<0.005). Also, there was significantly increase of NO and MDA levels and decrease of GSH levels in group 3 compared to other groups (p<0.005). Conclusions: hydrogen sulfide prevents kidney damage with antioxidant and antiinflammatory effect.
Collapse
Affiliation(s)
- Murat Dursun
- Department of Urology, Bahcelievler State Hospital, Istanbul, Turkey
| | - Alper Otunctemur
- Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Emin Ozbek
- Department of Urology, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Suleyman Sahin
- Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Huseyin Besiroglu
- Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | | | - Mustafa Cekmen
- Department of Biochemistry, Kocaeli University, Kocaeli, Turkey
| | - Adnan Somay
- Department of Pathology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| | - Nurver Ozbay
- Department of Pathology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| |
Collapse
|
|
17
|
Mazzei L, Docherty NG, Manucha W. Mediators and mechanisms of heat shock protein 70 based cytoprotection in obstructive nephropathy. Cell Stress Chaperones 2015; 20:893-906. [PMID: 26228633 PMCID: PMC4595437 DOI: 10.1007/s12192-015-0622-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Revised: 06/24/2015] [Accepted: 07/09/2015] [Indexed: 12/19/2022] Open
Abstract
Urinary heat shock protein 70 (Hsp70) is rapidly increased in patients with clinical acute kidney injury, indicating that it constitutes a component of the endogenous stress response to renal injury. Moreover, experimental models have demonstrated that Hsp70 activation is associated with the cytoprotective actions of several drugs following obstruction, including nitric oxide (NO) donors, geranylgeranylacetone, vitamin D, and rosuvastatin. Discrete and synergistic effects of the biological activities of Hsp70 may explain its cytoprotective role in obstructive nephropathy. Basic studies point to a combination of effects including inhibition of apoptosis and inflammation, repair of damaged proteins, prevention of unfolded protein aggregation, targeting of damaged protein for degradation, and cytoskeletal stabilization as primary effectors of Hsp70 action. This review summarizes our understanding of how the biological actions of Hsp70 may affect renal cytoprotection in the context of obstructive injury. The potential of Hsp70 to be of central importance to the mechanism of action of various drugs that modify the genesis of experimental obstructive nephropathy is considered.
Collapse
Affiliation(s)
- Luciana Mazzei
- Área de Farmacología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
- IMBECU-CONICET (National Council of Scientific and Technical Research of Argentina), Buenos Aires, Argentina.
| | - Neil G Docherty
- Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
| | - Walter Manucha
- Área de Farmacología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
- IMBECU-CONICET (National Council of Scientific and Technical Research of Argentina), Buenos Aires, Argentina
| |
Collapse
|
|
18
|
Otunctemur A, Ozbek E, Cakir SS, Dursun M, Cekmen M, Polat EC, Ozcan L, Somay A, Ozbay N. Beneficial effects montelukast, cysteinyl-leukotriene receptor antagonist, on renal damage after unilateral ureteral obstruction in rats. Int Braz J Urol 2015; 41:279-87. [PMID: 26005969 PMCID: PMC4752091 DOI: 10.1590/s1677-5538.ibju.2015.02.14] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Accepted: 07/27/2014] [Indexed: 02/07/2023] Open
Abstract
Introductıon Ureteral obstruction is a common pathology and caused kidney fibrosis and dysfunction at late period. In this present, we investigated the antifibrotic and antiinflammatory effects of montelukast which is cysteinyl leukotriene receptor antagonist, on kidney damage after unilateral ureteral obstruction(UUO) in rats. Mateirıals and Methods 32 rats divided four groups. Group 1 was control, group 2 was sham, group 3 was rats with UUO and group 4 was rats with UUO which were given montelukast sodium (oral 10 mg/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide(NO), malondialdehyde(MDA) and reduced glutathione(GSH) levels were determined in the other part of kidneys. Urea-creatinine levels were investigated at blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing for tubular necrosis and fibrosis in group 4(p<0.005). Also, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in group 3 compared the other groups(p<0.005). Conclusıon We can say that montelukast prevent kidney damage with antioxidant effect, independently of NO.
Collapse
Affiliation(s)
- Alper Otunctemur
- Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Emin Ozbek
- Department of Urology, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | | | - Murat Dursun
- Department of Urology, Bahcelievler State Hospital, Istanbul, Turkey
| | - Mustafa Cekmen
- Department of biochemistry, Kocaeli University, , Kocaeli, Turkey
| | - Emre Can Polat
- Department of Urology, Istanbul Medipol University, Faculty of Medicine, Istanbul, Turkey
| | - Levent Ozcan
- Department of Urology, Derince Training and Research Hospital, Kocaeli, Turkey
| | - Adnan Somay
- Department Pathology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| | - Nurver Ozbay
- Department Pathology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| |
Collapse
|
|
19
|
Seven A, Savran B, Koçak E, Tok S, Yüksel KB, Gözükara İ, Kabil Kucur S. Is there a correlation between maternal serum TGF-β1 levels and fetal hydronephrosis? J Matern Fetal Neonatal Med 2015; 29:1113-6. [DOI: 10.3109/14767058.2015.1036022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
|
|
20
|
Otunctemur A, Ozbek E, Cakir SS, Polat EC, Dursun M, Cekmen M, Somay A, Ozbay N. Pomegranate extract attenuates unilateral ureteral obstruction-induced renal damage by reducing oxidative stress. Urol Ann 2015; 7:166-71. [PMID: 25838069 PMCID: PMC4374253 DOI: 10.4103/0974-7796.150488] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Accepted: 06/24/2014] [Indexed: 02/07/2023] Open
Abstract
AIMS Ureteral obstruction may cause permanent kidney damage at late period. We know that the pomegranate extract (PE) play a strong role on removal of free oxygen radicals and prevention of oxidative stress. In the current study study, we evaluated the effect of PE on kidney damage after unilateral ureteral obstruction (UUO). SETTINGS AND DESIGN A total of 32 rats were divided into four groups. Group 1 was a control, Group 2 was a sham, Group 3 was rats with UUO and Group 4 was rats with UUO that were given PE (oral 100 μL/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. SUBJECTS AND METHODS Tubular necrosis, mononuclear cell infiltration, and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in the other part of kidneys. STATISTICAL ANALYSIS USED Statistical analyses were performed by the Chi-square test and one-way analysis of variance. RESULTS There was no difference significantly for urea-creatinine levels between groups. Pathologically, there was serious tubular necrosis, mononuclear cell infiltration and fibrosis in Group 3, and there was significantly decreasing for tubular necrosis, mononuclear cell infiltration and fibrosis in Group 4 (P < 0.005). Furthermore, there was significantly increasing for NO and MDA levels; decreasing for GSH levels in Group 3 compared the other groups (P < 0.005). CONCLUSIONS We think that the PE prevents kidney damage by decreasing oxidative stress in kidney.
Collapse
Affiliation(s)
- Alper Otunctemur
- Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Emin Ozbek
- Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | | | - Emre Can Polat
- Department of Urology, Istanbul Medipol University, Istanbul, Turkey
| | - Murat Dursun
- Department of Urology, Bahcelievler State Hospital, Istanbul, Turkey
| | - Mustafa Cekmen
- Department of Biochemistry, Kocaeli University, Kocaeli, Turkey
| | - Adnan Somay
- Department of Pathology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| | - Nurver Ozbay
- Department of Pathology, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey
| |
Collapse
|
|
21
|
Urinary TGF-1 has a supplementary value in predicting renal function recovery post unilateral ureteral obstruction. Int Urol Nephrol 2014; 47:33-7. [PMID: 25298140 DOI: 10.1007/s11255-014-0846-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Accepted: 09/09/2014] [Indexed: 02/07/2023]
Abstract
PURPOSE To evaluate whether urine transforming growth factor-β1 (TGF-β1) can help identifying kidneys that would recover their function after drainage of unilateral ureteric obstructive. METHODS Forty-five patients with unilateral ureteral obstruction were included. Glomerular filtration rate (GFR) of the obstructed kidney was <10 ml/min, and all patients were treated with percutaneous nephrostomy. TGF-β1 level was measured in the urine from the obstructed kidney at the time of drainage. GFR before nephrostomy insertion and 3 months after were calculated. RESULTS Patients with renal function improvement (significant increase in GFR) after nephrostomy insertion had significantly lower concentration of urine TGF-β1 (p<0.05) compared with the group that showed no change in GFR (non-functioning kidneys) The sensitivity, specificity and accuracy of urine TGF-β1 in identifying non-functioning kidney was 82, 82 and 82%, respectively. CONCLUSIONS Urine TGF-β1 is a cytokine leading to renal fibrosis and has a supplementary value in differentiating, at early stage, between kidneys that would recover function after releasing unilateral ureteral obstruction from those which will not (non-functioning kidneys).
Collapse
|
|
22
|
Hammad FT, Wheatley AM, Davis G. Bosentan normalizes the GFR response to renal nerve stimulation following reversible unilateral ureteric obstruction in the rat. Physiol Res 2014; 63:713-22. [PMID: 25157662 DOI: 10.33549/physiolres.932667] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
We investigated the renal response to direct renal nerve stimulation, 2 weeks following reversal of 24-h unilateral (left) ureteric obstruction. Renal nerve stimulation caused a 13-15 % fall in renal blood flow, in 4 groups of anesthetized rats following ureteric obstruction (n=9) or a sham operation (n=7) both with (n=9) and without (n=7) treatment with the mixed ET(A/B) receptor antagonist, bosentan. In the sham-operated rats, renal nerve stimulation did not change glomerular filtration rate but reduced urine flow rate (37+/-3 %, P<0.001), and absolute (38+/-4 %, P<0.001) and fractional (35+/-5 %, P<0.01) sodium excretion. Following unilateral ureteric obstruction, renal nerve stimulation increased glomerular filtration rate by 22+/-3 % (P<0.01), but reduced urine flow rate (14+/-2 %, P<0.001) and fractional sodium excretion (23+/-5 %, P<0.01). Bosentan treatment had no effect on baseline or renal responses to renal nerve stimulation in the sham group but normalized the renal response to renal nerve stimulation in the unilateral ureteric obstruction group. We conclude that 14 days after a 24-h period of unilateral ureteric obstruction there is an increase in GFR in response to direct renal nerve stimulation, which is due, in part, to the actions of endothelin at the time of obstruction.
Collapse
Affiliation(s)
- F T Hammad
- Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
| | | | | |
Collapse
|
|
23
|
González J, Valls N, Brito R, Rodrigo R. Essential hypertension and oxidative stress: New insights. World J Cardiol 2014; 6:353-366. [PMID: 24976907 PMCID: PMC4072825 DOI: 10.4330/wjc.v6.i6.353] [Citation(s) in RCA: 143] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2013] [Revised: 03/01/2014] [Accepted: 05/08/2014] [Indexed: 02/06/2023] Open
Abstract
Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated, a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents, such as superoxide anion, and antioxidant molecules, and leads to a decrease in nitric oxide bioavailability, which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides, such as angiotensin II, endothelin-1 and urotensin II, act through their receptors to stimulate the production of reactive oxygen species, by activating enzymes like NADPH oxidase and xanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents, including vitamin C and E, N-Acetylcysteine, polyphenols and selenium, among others. These substances have different therapeutic targets, but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.
Collapse
|
|
24
|
Diez ER, Altamirano LB, García IM, Mazzei L, Prado NJ, Fornes MW, Carrión FDC, Zumino AZP, Ferder L, Manucha W. Heart remodeling and ischemia-reperfusion arrhythmias linked to myocardial vitamin d receptors deficiency in obstructive nephropathy are reversed by paricalcitol. J Cardiovasc Pharmacol Ther 2014; 20:211-20. [PMID: 24924917 DOI: 10.1177/1074248414538704] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia-reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.
Collapse
Affiliation(s)
- Emiliano Raúl Diez
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina
| | - Liliana Berta Altamirano
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina Pathology Department, Medical Sciences College, National University of Cuyo, Mendoza, Argentina
| | - Isabel Mercedes García
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina
| | - Luciana Mazzei
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina
| | - Natalia Jorgelina Prado
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina
| | - Miguel Walter Fornes
- Institute of Histology and Embryology of Mendoza, National Scientific and Technical Research Council, Mendoza, Argentina
| | - Fernando Darío Cuello Carrión
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina
| | - Amira Zulma Ponce Zumino
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina
| | - León Ferder
- Department of Physiology and Pharmacology, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico
| | - Walter Manucha
- Institute of Medical and Experimental Biology of Cuyo, National Scientific and Technical Research Council, Mendoza, Argentina Pathology Department, Medical Sciences College, National University of Cuyo, Mendoza, Argentina
| |
Collapse
|
|
25
|
Abstract
PURPOSE OF REVIEW The prevalence of nephrolithiasis has been on the rise over recent decades. There have also been extensive efforts to identify risk factors for chronic kidney disease (CKD). The purpose of this review is to highlight recent evidence on the association of nephrolithiasis with the development of CKD and end-stage renal disease (ESRD). RECENT FINDINGS Several epidemiologic studies over the past decade assessed the relationship between history of nephrolithiasis and CKD. Across several studies, patients with nephrolithiasis had about a two-fold higher risk for decreased renal function or need for renal replacement therapy. This risk appears to be independent of risk factors for CKD that are common in stone formers such as hypertension and diabetes mellitus. Specific risk factors for CKD in stone formers include recurrent urinary tract infections, struvite and possibly uric acid stone composition, symptomatic stones, solitary kidney, ileal conduit, neurogenic bladder, and hydronephrosis. SUMMARY Recent evidence has shown a consistent relationship between nephrolithiasis history and an increased risk of CKD and ESRD. Understanding the characteristics that predispose to CKD may better inform how to optimally manage patients with nephrolithiasis and prevent this complication.
Collapse
|
|
26
|
Jia T, Olauson H, Lindberg K, Amin R, Edvardsson K, Lindholm B, Andersson G, Wernerson A, Sabbagh Y, Schiavi S, Larsson TE. A novel model of adenine-induced tubulointerstitial nephropathy in mice. BMC Nephrol 2013; 14:116. [PMID: 23718816 PMCID: PMC3682934 DOI: 10.1186/1471-2369-14-116] [Citation(s) in RCA: 155] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2012] [Accepted: 05/17/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND In vivo models of uremia are important tools to study numerous aspects of acute and chronic kidney disease. Mouse models are pivotal because most genetically engineered animal models are mice, which allow dissecting the impact of selected target genes in renal failure. Adenine-based protocols to induce renal failure are available in rats, but have not been adapted in mice due to their reluctance to consume adenine. In the current paper we developed a novel method for induction of renal failure through dietary delivery of adenine mixed in a casein-based diet. RESULTS After an induction phase, a stable model of renal impairment was obtained (target urea range 80-100 mg/dL), mimicking several aspects of chronic kidney disease - mineral and bone disorder including secondary hyperparathyroidism, bone abnormalities and pathological elevation of FGF23. No deaths occurred and the level of uremia was adaptable through adjustments of the adenine content, providing significant advantages compared to existing models. In an 8-week proof-of-concept study, renal histology showed mainly a tubulointerstitial damage with infiltrating leukocytes, interstitial edema and widening of the Bownman's space. Fibrosis was present in most animals as defined by histology and gene expression changes of fibrosis markers. Parathyroid cell proliferation was markedly increased but without signs of glandular hypertrophy. Skeletal histology showed increased trabecular bone and bone marrow adiposity whereas bone biomarkers (CTX and PINP) suggested higher bone formation, but surprisingly, lower bone resorption and perturbations in mineral metabolism. CONCLUSIONS We present a novel, non-surgical method for induction of renal failure in mice. This is an important complement to existing uremic models for pathophysiological studies in acute and chronic kidney disease, especially in terms of tubulointerstitial lesions.
Collapse
|
|
27
|
Piccoli GB, Attini R, Parisi S, Vigotti FN, Daidola G, Deagostini MC, Ferraresi M, De Pascale A, Porpiglia F, Veltri A, Todros T. Excessive urinary tract dilatation and proteinuria in pregnancy: a common and overlooked association? BMC Nephrol 2013; 14:52. [PMID: 23446427 PMCID: PMC3600000 DOI: 10.1186/1471-2369-14-52] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2012] [Accepted: 02/07/2013] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Proteinuria and dilatation of the urinary tract are both relatively common in pregnancy, the latter with a spectrum of symptoms, from none to severe pain and infection. Proteinuria is a rare occurrence in acute obstructive nephropathy; it has been reported in pregnancy, where it may pose a challenging differential diagnosis with pre-eclampsia.The aim of the present study is to report on the incidence of proteinuria (≥ 0.3; ≥ 0.5 g/day) in association with symptomatic-severe urinary tract dilatation in pregnancy. METHODS Case series. SETTING Nephrological-Obstetric Unit dedicated to pregnancy and kidney diseases (January 2000-April 2011). SOURCE database prospectively updated since the start of the Unit. Retrospective review of clinical charts identified as relevant on the database, by a nephrologist and an obstetrician. RESULTS From January 2000 to April 2011, 262 pregnancies were referred. Urinary tract dilatation with or without infection was the main cause of referral in 26 cases (predominantly monolateral in 19 cases): 23 singletons, 1 lost to follow-up, 1 twin and 1 triplet. Patients were referred for urinary tract infection (15 cases) and/or renal pain (10 cases); 6 patients were treated by urologic interventions ("JJ" stenting). Among them, 11 singletons and 1 triple pregnancy developed proteinuria ≥ 0.3 g/day (46.1%). Proteinuria was ≥ 0.5 g/day in 6 singletons (23.1%). Proteinuria resolved after delivery in all cases. No patient developed hypertension; in none was an alternative cause of proteinuria evident. No significant demographic difference was observed in patients with renal dilatation who developed proteinuria versus those who did not. An association with the presence of "JJ" stenting was present (5/6 cases with proteinuria ≥ 0.5 g/day), which may reflect both severer obstruction and a role for vescico-ureteral reflux, induced by the stent. CONCLUSIONS Symptomatic urinary tract dilatation may be associated with proteinuria in pregnancy. This association should be kept in mind in the differential diagnosis with other causes of proteinuria in pregnancy, including pre-eclampsia.
Collapse
|
|
28
|
Yasar A, Erdemir F, Parlaktas BS, Atilgan D, Koseoglu RD, Saylan O, Firat F. The effect of carvedilol on serum and tissue oxidative stress parameters in partial ureteral obstruction induced rat model. Kaohsiung J Med Sci 2013; 29:19-25. [DOI: 10.1016/j.kjms.2012.08.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2011] [Accepted: 10/05/2011] [Indexed: 02/07/2023] Open
|
|
29
|
Atılgan D, Parlaktas BS, Uluocak N, Erdemir F, Fırat F, Erkorkmaz U, Saylan O. Effects of melatonin on partial unilateral ureteral obstruction induced oxidative injury in rat kidney. Urol Ann 2012; 4:89-93. [PMID: 22629003 PMCID: PMC3355707 DOI: 10.4103/0974-7796.95552] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2011] [Accepted: 08/14/2011] [Indexed: 02/07/2023] Open
Abstract
AIM This experimental study was designed to produce ischemia-reperfusion injury in rat kidney by performing partial unilateral ureteral obstruction (PUUO) and investigated the effects of melatonin on the levels of oxidative injury parameters. MATERIALS AND METHODS Twenty-four adult male rats were randomly divided into three groups as follows; control group (Group 1); only nephrectomy and blood (5 ml) drawn from vena cava inferior, PUUO group (Group 2); PUUO (10 days)+ipsilateral nephrectomy after recovery of PUUO+blood from vena cava inferior VCI, melatonin treated group (Group 3); PUUO (10 days)+melatonin (1/2 hr before release, 50 mg/kg, ip)+ipsilateral nephrectomy after recovery of PUUO+blood from VCI. The left ureter was embedded into the psoas muscle to create PUUO. After 10 days, PUUO was recovered and ipsilateral nephrectomies were performed for biochemical analysis of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and protein carbonyl (PC) in the tissues and blood was drawn from inferior vena cava to study the same parameters in systemic circulation. The results were compared statistically. RESULTS The blood levels of MDA, NO, and PC were increased in the PUUO group in comparison to the sham-operated group (P<0.05). Melatonin treatment reduced MDA, NO, and PC levels in blood after PUUO recovery, but statistically significance consisted only for MDA and NO (P<0.05). The antioxidant enzyme activities (SOD, GSH-Px) were increased in the PUUO group (P<0.05). Melatonin treatment reduced SOD and GSH-Px activities in comparison with the sham-operated control group (P<0.05). Similarly, renal tissue levels of MDA, NO, and PC were increased in the PUUO group in comparison with the sham-operated group (P<0.05). Melatonin treatment ameliorated MDA, NO, and PC levels in renal tissue after PUUO recovery only MDA was statistically significant (P<0.05). Antioxidant enzyme activities (SOD, CAT, and GSH-Px) were increased in the PUUO group. Melatonin treatment caused reduction in SOD, CAT, and GSH-Px activities in comparison to the sham-operated control group (P<0.05). CONCLUSION The results of this study showed that experimentally induced PUUO caused oxidative stress in rat kidney and melatonin treatment reduced oxidative stress and therefore may have a preventive effect on PUUO induced oxidative kidney damage in rats.
Collapse
Affiliation(s)
- Dogan Atılgan
- Department of Urology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey
| | | | | | | | | | | | | |
Collapse
|
|
30
|
Ampawong S, Klincomhum A, Likitsuntonwong W, Singha O, Ketjareon T, Panavechkijkul Y, Zaw KM, Kengkoom K. Expression of Aquaporin-1, -2 and -4 in Mice with a Spontaneous Mutation Leading to Hydronephrosis. J Comp Pathol 2012; 146:332-7. [DOI: 10.1016/j.jcpa.2011.08.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2011] [Revised: 07/21/2011] [Accepted: 08/11/2011] [Indexed: 11/16/2022]
|
|
31
|
García IM, Altamirano L, Mazzei L, Fornés M, Molina MN, Ferder L, Manucha W. Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy. Am J Physiol Renal Physiol 2012; 302:F1595-605. [PMID: 22492946 DOI: 10.1152/ajprenal.00617.2011] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Vitamin D slows the progression of chronic kidney disease. Furthermore, activators of vitamin D receptors (VDR) have suppressant effects on the renin-angiotensin system, as well as anti-inflammatory and antifibrotic actions. This study aimed to evaluate the cytoprotective effects of paricalcitol, a VDR activator, at the mitochondrial level using an obstructive nephropathy model [unilateral ureteral obstruction (UUO)]. Rats subjected to UUO and controls were treated daily with vehicle or paricalcitol. The control group underwent a sham surgery. The treatment was done for 15 days (30 ng/kg). The following were determined: biochemical parameters; fibrosis; apoptosis; mitochondrial morphology; VDR, AT(1) receptor, and NADPH oxidase 4 expression; and NADPH oxidase activity (in total and in mitochondrial fractions from the renal cortex). VDR activation prevented fibrosis (20 ± 5 vs. 60 ± 10%) and the number of TUNEL-positive apoptotic cells (10 ± 3 vs. 25 ± 4) in UUO. Biochemical, histological, and molecular studies suggest mitochondrial injury. Electron microscopy revealed in UUO electronically luminous material in the nucleus. Some mitochondria were increased in size and contained dilated crests and larger than normal spaces in their interiors. These changes were not present with paricalcitol treatment. Additionally, high AT(1)-receptor mRNA and NADPH activity was reverted in mitochondrial fractions from obstructed paricalcitol-treated animals (0.58 ± 0.06 vs. 0.95 ± 0.05 relative densitometry units and 9,000 ± 800 vs. 15,000 ± 1,000 relative fluorescence units·μg protein(-1)·min(-1), respectively). These changes were consistent with an improvement in VDR expression (0.75 ± 0.05 vs. 0.35 ± 0.04 relative densitometry units). These results suggest that paricalcitol confers a protective effect and reveal, as well, a possible AT(1) receptor-dependent protective effect that occurs at the mitochondrial level.
Collapse
Affiliation(s)
- Isabel Mercedes García
- Área de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina
| | | | | | | | | | | | | |
Collapse
|
|
32
|
ZIEG JAKUB, BLAHOVA KVETA, SEEMAN TOMAS, BRONSKY JIRI, DVORAKOVA HANA, PECHOVA MARTA, JANDA JAN, MATOUSOVIC KAREL. Urinary transforming growth factor-β1 in children with obstructive uropathy. Nephrology (Carlton) 2011; 16:595-8. [DOI: 10.1111/j.1440-1797.2011.01459.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
33
|
Yuan Q, Wang R, Peng Y, Fu X, Wang W, Wang L, Zhang F, Peng Z, Ning W, Hu G, Wang Z, Tao L. Fluorofenidone attenuates tubulointerstitial fibrosis by inhibiting TGF-β(1)-induced fibroblast activation. Am J Nephrol 2011; 34:181-94. [PMID: 21791914 DOI: 10.1159/000329080] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2011] [Accepted: 04/30/2011] [Indexed: 12/28/2022]
Abstract
BACKGROUND Novel therapeutic agents are urgently needed to combat renal fibrosis. The purpose of this study was to assess, using complete unilateral ureteral obstruction (UUO) in rats, whether fluorofenidone (AKF-PD) [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone] inhibits renal fibrosis, and to determine whether it exerts its inhibitory function on renal fibroblast activation. METHODS Sprague-Dawley rats were randomly divided into 3 groups: sham operation, UUO and UUO/AKF-PD (500 mg/kg/day). Renal function, tubulointerstitium damage index score, extracellular matrix (ECM) deposition, and the expressions of TGF-β(1), collagen III, α-SMA, p-Smad2, p-Smad3, p-ERK1/2, p-JNK and p-p38 were measured. In addition, the expressions of α-SMA, fibronectin, CTGF, p-Smad2/3, p-ERK1/2, p-p38 and p-JNK were measured in TGF-β(1)-stimulated normal rat renal fibroblasts (NRK-49F). RESULTS AKF-PD treatment significantly attenuated tubulointerstitium damage, ECM deposition, the expressions of TGF-β(1), collagen III, α-SMA, p-ERK1/2, p-p38 and p-JNK in vivo. In vitro, AKF-PD dose-dependently inhibited expressions of α-SMA, fibronectin and CTGF. Furthermore, AKF-PD did not inhibit Smad2/3 phosphorylation or nuclear accumulation, but rather attenuated ERK, p38 and JNK activation. CONCLUSION AKF-PD treatment inhibits the progression of renal interstitial fibrosis in obstructed kidneys; this is potentially achieved by suppressing fibroblast activation. Therefore, AKF-PD is a special candidate for the treatment of renal fibrosis.
Collapse
Affiliation(s)
- Qiongjing Yuan
- Division of Nephrology, Xiangya Hospital, Central South University, Changsha, China
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Karabuga İ, Akbay K, Turna B, Vatansever HS, Altay B, Güzel E, Turkoz Uluer E, Ustun G, Ekren F, Nazli O, Muftuoglu S, Apaydin E. Effect of lisinopril on renal tissue damage in unilateral ureteral obstruction in rats. ACTA ACUST UNITED AC 2011; 40:27-34. [DOI: 10.1007/s00240-011-0393-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2010] [Accepted: 05/25/2011] [Indexed: 02/07/2023]
|
|
35
|
Prunotto M, Gabbiani G, Pomposiello S, Ghiggeri G, Moll S. The kidney as a target organ in pharmaceutical research. Drug Discov Today 2011; 16:244-59. [DOI: 10.1016/j.drudis.2010.11.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2010] [Revised: 11/11/2010] [Accepted: 11/24/2010] [Indexed: 02/07/2023]
|
|
36
|
Rodrigo R, González J, Paoletto F. The role of oxidative stress in the pathophysiology of hypertension. Hypertens Res 2011; 34:431-40. [PMID: 21228777 DOI: 10.1038/hr.2010.264] [Citation(s) in RCA: 284] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hypertension is considered to be the most important risk factor in the development of cardiovascular disease. An increasing body of evidence suggests that oxidative stress, which results in an excessive generation of reactive oxygen species (ROS), has a key role in the pathogenesis of hypertension. The modulation of the vasomotor system involves ROS as mediators of vasoconstriction induced by angiotensin II, endothelin-1 and urotensin-II, among others. The bioavailability of nitric oxide (NO), which is a major vasodilator, is highly dependent on the redox status. Under physiological conditions, low concentrations of intracellular ROS have an important role in the normal redox signaling maintaining vascular function and integrity. However, under pathophysiological conditions, increased levels of ROS contribute to vascular dysfunction and remodeling through oxidative damage. In human hypertension, an increase in the production of superoxide anions and hydrogen peroxide, a decrease in NO synthesis and a reduction in antioxidant bioavailability have been observed. In turn, antioxidants are reducing agents that can neutralize these oxidative and otherwise damaging biomolecules. The use of antioxidant vitamins, such as vitamins C and E, has gained considerable interest as protecting agents against vascular endothelial damage. Available data support the role of these vitamins as effective antioxidants that can counteract ROS effects. This review discusses the mechanisms involved in ROS generation, the role of oxidative stress in the pathogenesis of vascular damage in hypertension, and the possible therapeutic strategies that could prevent or treat this disorder.
Collapse
Affiliation(s)
- Ramón Rodrigo
- Renal Pathophysiology Laboratory, Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
| | | | | |
Collapse
|
|
37
|
Akgül T, Huri E, Yagmurdur H, Ayyıldız A, Üstün H, Germiyanoğlu C. Phosphodiesterase 5 inhibitors attenuate renal tubular apoptosis after partial unilateral ureteral obstruction: An experimental study. Kaohsiung J Med Sci 2011; 27:15-9. [DOI: 10.1016/j.kjms.2010.03.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2009] [Accepted: 03/19/2010] [Indexed: 02/07/2023] Open
|
|
38
|
Nakanishi T, Morokata T, Noto T, Kubo K, Umeno H, Kinugasa F, Eikyu Y, Kozuki Y, Seki N. Effect of the inosine 5'-monophosphate dehydrogenase inhibitor BMS-566419 on renal fibrosis in unilateral ureteral obstruction in rats. Int Immunopharmacol 2010; 10:1434-9. [PMID: 20832515 DOI: 10.1016/j.intimp.2010.08.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2010] [Revised: 08/12/2010] [Accepted: 08/18/2010] [Indexed: 02/07/2023]
Abstract
Chronic allograft nephropathy (CAN) is a major cause of late allograft loss. One morphological characteristic of CAN is renal interstitial fibrosis. Mycophenolate mofetil (MMF), the inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitor, has been reported to attenuate the progression of renal interstitial fibrosis. However, the question of whether the newly synthesized IMPDH inhibitors with structures different from MMF have an antifibrotic effect remains unanswered. We evaluated the antifibrotic effects of BMS-566419, a chemically synthesized IMPDH inhibitor, using an experimental rat model, unilateral ureteral obstruction (UUO), in comparison with those of MMF. Expression levels of monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta1 (TGF-β1), which play important roles in UUO-induced renal fibrosis, were also investigated to determine the mechanism by which BMS-566419 affects the progression of renal fibrosis. After 14 days of UUO, interstitial fibrosis was frequently observed in the renal cortex of rats administered vehicle control. BMS-566419 by oral administration showed a significant and dose-dependent suppressive effect on UUO-induced renal fibrosis in histopathological experiments. BMS-566419 treatment also decreased collagen content, as indicated by hydroxyproline concentration, and the expression of collagen type 1 mRNA. BMS-566419 also decreased the expression of mRNA for both MCP-1 and TGF-β1. The antifibrotic effects of treatment with BMS-566419 at 60 mg/kg seemed comparable to those with MMF at 40 mg/kg. These results suggest that BMS-566419 and other chemically synthesized IMPDH inhibitors have beneficial pharmacological effects similar to those of MMF, and are potential pharmaceutical candidates in the treatment of fibrotic renal disease, including CAN.
Collapse
Affiliation(s)
- Tomonori Nakanishi
- Pharmacology Research Laboratories, Astellas Pharma Inc., Tsukuba-shi, Ibaraki, Japan.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Chen L, Faulhaber-Walter R, Wen Y, Huang Y, Mizel D, Chen M, Sequeira Lopez ML, Weinstein LS, Gomez RA, Briggs JP, Schnermann J. Renal failure in mice with Gsalpha deletion in juxtaglomerular cells. Am J Nephrol 2010; 32:83-94. [PMID: 20551626 DOI: 10.1159/000314635] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2010] [Accepted: 04/23/2010] [Indexed: 11/19/2022]
Abstract
BACKGROUND Mice with deletion of Gsalpha in renin-producing cells (RC/FF mice) have been shown to have greatly reduced renin production and lack of responsiveness of renin secretion to acute stimuli. In addition, young RC/FF mice are hypotensive and have a vasopressin-resistant concentrating defect. In the present study we have determined the long-term effect on renal function, blood pressure, and renal pathology in this low renin and diuretic mouse model. METHODS AND RESULTS Urine osmolarity of RC/FF mice was decreased in all age groups. GFR measured at 7, 14 and 20 weeks of age declined progressively. Single nephron GFR similarly declined while fractional proximal fluid absorption was maintained. Expression levels of extracellular matrix proteins (collagen I, IV and fibronectin) and alpha-smooth muscle actin were increased in kidneys of RC/FF mice at 20 weeks, and this was accompanied by focal segmental glomerulosclerosis and periglomerular interstitial fibrosis. RC/FF mice showed a progressive reduction of body weight, an increase in urine albumin excretion, and an increase of blood pressure with aging. CONCLUSION A chronic reduction of renin production in mice may be a risk factor in its own right, and does not protect renal function against the profibrotic influence of a chronically elevated urine flow.
Collapse
Affiliation(s)
- Limeng Chen
- National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Md., USA.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Grande MT, Pérez-Barriocanal F, López-Novoa JM. Role of inflammation in túbulo-interstitial damage associated to obstructive nephropathy. JOURNAL OF INFLAMMATION-LONDON 2010; 7:19. [PMID: 20412564 PMCID: PMC2873503 DOI: 10.1186/1476-9255-7-19] [Citation(s) in RCA: 121] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2009] [Accepted: 04/22/2010] [Indexed: 02/07/2023]
Abstract
Obstructive nephropathy is characterized by an inflammatory state in the kidney, that is promoted by cytokines and growth factors produced by damaged tubular cells, infiltrated macrophages and accumulated myofibroblasts. This inflammatory state contributes to tubular atrophy and interstitial fibrosis characteristic of obstructive nephropathy. Accumulation of leukocytes, especially macrophages and T lymphocytes, in the renal interstitium is strongly associated to the progression of renal injury. Proinflammatory cytokines, NF-κB activation, adhesion molecules, chemokines, growth factors, NO and oxidative stress contribute in different ways to progressive renal damage induced by obstructive nephropathy, as they induce leukocytes recruitment, tubular cell apoptosis and interstitial fibrosis. Increased angiotensin II production, increased oxidative stress and high levels of proinflammatory cytokines contribute to NF-κB activation which in turn induce the expression of adhesion molecules and chemokines responsible for leukocyte recruitment and iNOS and cytokines overexpression, which aggravates the inflammatory response in the damaged kidney. In this manuscript we revise the different events and regulatory mechanisms involved in inflammation associated to obstructive nephropathy.
Collapse
Affiliation(s)
- María T Grande
- Instituto "Reina Sofía" de Investigación Nefrológica, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain.
| | | | | |
Collapse
|
|
41
|
Comparison of the effects of l-carnitine and α-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats. ACTA ACUST UNITED AC 2009; 38:187-94. [PMID: 19940986 DOI: 10.1007/s00240-009-0238-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2009] [Accepted: 11/04/2009] [Indexed: 02/07/2023]
|
|
42
|
Ozbek E, Ilbey YO, Ozbek M, Simsek A, Cekmen M, Somay A. Melatonin attenuates unilateral ureteral obstruction-induced renal injury by reducing oxidative stress, iNOS, MAPK, and NF-kB expression. J Endourol 2009; 23:1165-73. [PMID: 19530942 DOI: 10.1089/end.2009.0035] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To investigate whether melatonin (MLT) treatment has any protective effect on unilateral ureteral obstruction (UUO)-induced kidney injury in rats. MATERIALS AND METHODS Six animals were included in each of the following five groups: group 1, sham operation but no treatment; group 2, unilateral ureteral ligation but no treatment; group 3, sham operation + MLT; group 4, unilateral ureteral ligation + MLT; group 5, unilateral ureteral ligation +5% ethanol (the vehicle of MLT). The injected dose of MLT was 1 mg/kg/day (intraperitoneal). MLT and vehicle were injected daily, beginning 5 days before the unilateral ureteral ligation or sham operation and until 10 days after it. At 10 days after UUO, all rats were sacrificed with high-dose ketamine. Malondialdehyde, glutathione, nitric oxide (NO), and 8-hydroxydeoxyguanosine levels and inducible NO synthase (iNOS), p38-mitogen-activated protein kinase (p38-MAPK), and nuclear factor kappa B (NF-kB) expression were studied. Histopathological examination of the obstructed kidney was also performed. RESULTS UUO was accompanied by a significant increase in malondialdehyde, NO, and 8-hydroxydeoxyguanosine along with a significant decrease in glutathione levels in the kidney tissue, as well as a significant elevation in iNOS, p38-MAPK, and NF-kB expression. MLT treatment resulted in reduction of the parameters of oxidative stress and the iNOS, p38-MAPK, and NF-kB expression. MLT treatment also reduced the development of leukocyte infiltration and interstitial fibrosis in UUO rats. CONCLUSIONS MLT may prevent UUO-induced kidney damage in rats by reducing oxidative stress. The mechanism for this is likely mediated via reduction in the expression of iNOS, p38-MAPK, and NF-kB, since MLT reduces the activation of these pathways.
Collapse
Affiliation(s)
- Emin Ozbek
- Department of Urology, Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Istanbul, Turkey
| | | | | | | | | | | |
Collapse
|
|
43
|
Loru D, Incani A, Deiana M, Corona G, Atzeri A, Melis MP, Rosa A, Dessì MA. Protective effect of hydroxytyrosol and tyrosol against oxidative stress in kidney cells. Toxicol Ind Health 2009; 25:301-10. [DOI: 10.1177/0748233709103028] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Bioavailability studies in animals and humans fed with extravirgin olive oil demonstrated that hydroxytyrosol and tyrosol, the major simple phenolic compounds in extravirgin olive oil, are dose-dependently absorbed and excreted. Once absorbed, they undergo extensive metabolism; hydroxytyrosol and tyrosol concentrate mainly in the kidney, where they may exert an important role in the prevention of oxidative stress induced renal dysfunction. In this study we monitored the ability of hydroxytyrosol and tyrosol to protect renal cells (LLC-PK1) following oxidative damage induced by H2O2. Oxidative stress was evaluated by monitoring the changes of the membrane lipid fraction. Hydroxytyrosol exerted a significant antioxidant action, inhibiting the production of MDA, fatty acids hydroperoxides and 7-ketocholesterol, major oxidation products of unsaturated fatty acids and cholesterol, and thus protecting the cells from H2O2-induced damage. Tyrosol, instead, in this experimental model, did not exert any protective effect.
Collapse
Affiliation(s)
- D Loru
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| | - A Incani
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| | - M Deiana
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| | - G Corona
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| | - A Atzeri
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| | - MP Melis
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| | - A Rosa
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| | - MA Dessì
- Dipartimento di Biologia Sperimentale, Sezione di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, Km 4.5 09142 Monserrato (CA), Italy
| |
Collapse
|
|
44
|
Russ AL, Dadarlat IA, Haberstroh KM, Rundell AE. Investigating the role of ischemia vs. elevated hydrostatic pressure associated with acute obstructive uropathy. Ann Biomed Eng 2009; 37:1415-24. [PMID: 19381812 DOI: 10.1007/s10439-009-9695-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2008] [Accepted: 04/07/2009] [Indexed: 11/29/2022]
Abstract
Obstructive uropathy can cause irreversible renal damage. It has been hypothesized that elevated hydrostatic pressure within renal tubules and/or renal ischemia contributes to cellular injury following obstruction. However, these assaults are essentially impossible to isolate in vivo. Therefore, we developed a novel pressure system to evaluate the isolated and coordinated effects of elevated hydrostatic pressure and ischemic insults on renal cells in vitro. Cells were subjected to: (1) elevated hydrostatic pressure (80 cm H(2)O); (2) ischemic insults (hypoxia (0% O(2)), hypercapnia (20% CO(2)), and 0 mM glucose media); and (3) elevated pressure + ischemic insults. Cellular responses including cell density, lactate dehydrogenase (LDH) release, and intracellular LDH (LDH(i)), were recorded after 24 h of insult and following recovery. Data were analyzed to assess the primary effects of ischemic insults and elevated pressure. Unlike pressure, ischemic insults exerted a primary effect on nearly all response measurements. We also evaluated the data for insult interactions and identified significant interactions between ischemic insults and pressure. Altogether, findings indicate that pressure may sub-lethally effect cells and alter cellular metabolism (LDH(i)) and membrane properties. Results suggest that renal ischemia may be the primary, but not the sole, cause of cellular injury induced by obstructive uropathy.
Collapse
Affiliation(s)
- Alissa L Russ
- Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Dr., West Lafayette, IN 47907-1791, USA.
| | | | | | | |
Collapse
|
|
45
|
Radović N, Cuzić S, Knotek M. Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule and interstitial cell apoptosis in rats. Croat Med J 2009; 49:600-7. [PMID: 18925693 DOI: 10.3325/cmj.2008.5.600] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM To investigate the effects of angiotensin-converting enzyme inhibitor (cilazapril) and angiotensin II type I receptor antagonist (losartan) on tubular and interstitial cell apoptosis and caspase-3 activity in rats with obstructive nephropathy after unilateral ureteral obstruction. METHODS Rats with unilateral obstructive nephropathy and sham-operated rats were treated with cilazapril, losartan, or the vehicle (water). Tubular and interstitial cell apoptosis was detected morphologically on hematoxylin and eosin-stained renal specimens and by the terminal deoxynucleotidyl transferase-mediated nick end-labeling. Caspase-3 activity in whole-kidney tissue homogenates was measured colorimetrically. RESULTS After unilateral ureter ligation, there was a significant increase in the number of apoptotic tubular and interstitial cells in the obstructed kidney (P=0.049 and P=0.036, respectively, vs sham-operated rats, 10 days after ligation). In rats with unilateral obstructive nephropathy, neither cilazapril nor losartan had an effect on tubular cell apoptosis. However, cilazapril caused a significant increase in the number of renal apoptotic interstitial cells (P=0.019). Caspase-3 activity was not significantly different in rats with unilateral obstructive nephropathy than in sham-operated rats. CONCLUSION Rats with unilateral obstructive nephropathy had increased apoptosis of tubular and interstitial cells in comparison with sham-operated rats. Neither cilazapril nor losartan had an effect on tubular cell apoptosis, and cilazapril even increased interstitial cell apoptosis.
Collapse
Affiliation(s)
- Nikola Radović
- Department of Urology, Dubrava University Hospital, Zagreb, Croatia.
| | | | | |
Collapse
|
|
46
|
MR urography: technique and results for the evaluation of urinary obstruction in the pediatric population. Magn Reson Imaging Clin N Am 2008; 16:643-60, viii-ix. [PMID: 18926428 DOI: 10.1016/j.mric.2008.07.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
MR urography has the potential to revolutionize imaging of the urinary tract in both adults and children, because of its ability to provide an unprecedented level of anatomic information and quantitative functional evaluation of each kidney. MR urography can now provide useful assessment of obstructive uropathy and may provide predictive information about which children will benefit from surgery. It has the potential to identify parameters that indicate a significant obstruction as opposed to self-limited hydronephrosis. Further technical developments in the field will produce greater insights into the pathophysiology of not only urologic disorders but also disorders of the kidney itself.
Collapse
|
|
47
|
Zecher M, Guichard C, Velásquez MJ, Figueroa G, Rodrigo R. Implications of oxidative stress in the pathophysiology of obstructive uropathy. ACTA ACUST UNITED AC 2008; 37:19-26. [PMID: 19082822 DOI: 10.1007/s00240-008-0163-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2008] [Accepted: 11/25/2008] [Indexed: 02/07/2023]
Abstract
Although the functional and clinical alterations occurring in patients with obstructive uropathy are not well understood, it has been suggested that oxidative stress could contribute in the mechanism responsible for the impairment of sodium and water balance. This study aimed to test the hypothesis that red wine administration causes an amelioration of both the renal damage and impairment of renal Na(+), K(+)-ATPase activity occurring after ureteral obstruction in the rat. Twenty-four male Wistar adult rats weighting 200-250 g were used. Half of them received a 10-week treatment with wine as the sole fluid source, while the other group received water. Both groups were subjected to 24-h unilateral ureteral obstruction (UUO). Kidney tissue was collected following the relief of the ligature to perform the biochemical assessments. Urine and blood samples were taken at baseline and after the relief. Results show that the treatment with red wine significantly enhances the activity of antioxidant enzymes, and thus reduces renal lipid peroxidation secondary to UUO, which correlated negatively with Na(+), K(+)-ATPase activity. Based on this and other previous data, it could be suggested that red wine administration may prevent renal damage secondary to UUO by inducing enhanced antioxidant potential.
Collapse
Affiliation(s)
- Martin Zecher
- Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, Santiago, Chile
| | | | | | | | | |
Collapse
|
|
48
|
Barros M, Martinelli R, Rocha H. Experimental supratrigonal cystectomy: II--Evaluation of urinary calculi, infection, and bladder dysfunction in the pathogenesis of renal failure. Int Urol Nephrol 2008; 40:329-32. [PMID: 18085427 DOI: 10.1007/s11255-007-9287-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2007] [Accepted: 09/04/2007] [Indexed: 01/25/2023]
Abstract
The objective of this study was to evaluate the role of urolithiasis, infection, and bladder dysfunction in the pathogenesis of renal failure in rats subjected to supratrigonal cystectomy. One group of Sprague-Dawley rats was submitted to supratrigonal cystectomy, a second to cystectomy during which a suspension of Proteus mirabilis was injected into the bladder stump, and a third to sham surgery (controls). The animals were sacrificed two months after surgery. Blood pressure and serum urea and creatinine were measured before surgery and at sacrifice when a careful inspection of the urinary tract was performed to determine the presence of hydronephrosis and calculi. Microbiological analyses were performed on urine aspirated from the bladder and on the kidneys. Significant differences were found between values of systolic blood pressure and serum urea and creatinine recorded prior to the surgical procedure and those recorded at sacrifice in each group except the control group. Renal failure was present in all animals subjected to cystectomy. Urinary calculi were documented in 5/10 animals subjected to cystectomy only and in all rats inoculated with P. mirabilis. Hypertension was documented in 43.75% of animals subjected to cystectomy. Pyelonephritis was diagnosed only in animals with urinary calculi, in each of which urine culture was also positive. No cases of renal failure, hypertension, calculi, and/or pyelonephritis were detected in the sham group. The findings of this study indicate that kidney failure in rats subjected to supratrigonal cystectomy is related to the severe bladder dysfunction induced by the surgical procedure.
Collapse
Affiliation(s)
- Milton Barros
- Department of Urology, School of Medicine, Federal University of Bahia, Salvador, Bahia, Brazil.
| | | | | |
Collapse
|
|
49
|
Abstract
Magnetic resonance (MR) urography is a powerful tool that fuses anatomic information with functional data in a single test without the use of ionizing radiation. This article provides an overview of the technical aspects of MR urography and common clinical applications, such as the evaluation of hydronephrosis, reflux nephropathy, and renal dysplasia.
Collapse
|
|
50
|
Dong X, Bachman LA, Miller MN, Nath KA, Griffin MD. Dendritic cells facilitate accumulation of IL-17 T cells in the kidney following acute renal obstruction. Kidney Int 2008; 74:1294-309. [PMID: 18974760 DOI: 10.1038/ki.2008.394] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Acute urinary obstruction causes interstitial inflammation with leukocyte accumulation and the secretion of soluble mediators. Here we show that unilateral ureteral ligation caused a progressive increase in renal F4/80(+) and F4/80(-) dendritic cells, monocytes, neutrophils and T-cells 24-72 h following obstruction. Depletion of dendritic cells by clodronate pretreatment showed these cells to be the most potent source of tumor necrosis factor and other pro-inflammatory mediators in the obstructed kidney. F4/80(+) dendritic cells and T-cells co-localized in the cortico-medullary junction and cortex of the obstructed kidney. Cytokine secretion patterns and surface phenotypes of T-cells from obstructed kidneys were found to include interferon-gamma-secreting CD4(+) and CD8(+) memory T-cells as well as interleukin 17 (IL-17)-secreting CD4(+) memory T-cells. Depletion of the intra-renal dendritic cells prior to ligation did not numerically reduce T-cells in obstructed kidneys but attenuated interferon-gamma and IL-17-competent T-cells. Our study shows that intra-renal dendritic cells are a previously unidentified early source of proinflammatory mediators after acute urinary obstruction and play a specific role in recruitment and activation of effector-memory T-cells including IL-17-secreting CD4(+) T-cells.
Collapse
Affiliation(s)
- Xiangyang Dong
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | | | | | | | | |
Collapse
|