|
1
|
Sankaran SS, Dewan P, Malhotra RK, Harit D, Kashyap B, Yadav M, Khalsa MS. Glutamine Mouthwash for Preventing Methotrexate-Induced Mucositis in Children with Acute Lymphoblastic Leukemia: A Randomized Cross-Over Trial. Indian Pediatr 2025; 62:269-275. [PMID: 40198535 DOI: 10.1007/s13312-025-00042-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 02/11/2025] [Indexed: 04/10/2025]
Abstract
OBJECTIVE To assess the efficacy of glutamine mouthwash versus standard oral hygiene protocol (SOHP) in reducing the overall incidence, duration and severity of oral mucositis in children with acute lymphoblastic leukemia (ALL) receiving High Dose Methotrexate (HDMTX). METHODS In this cross-over trial, children with ALL due to receive four courses of HDMTX (2 g/m2/dose) (on days 8, 22, 36, and 50 of consolidation) were randomized to receive two consecutive courses of HDMTX with glutamine mouthwash plus SOHP, followed by two HDMTX courses with SOHP only; or vice-versa. Glutamine suspension was administered twice daily by swish and swallow technique, starting one day before the course of HDMTX and continued upto 7 days or till mucositis persisted. SOHP comprised supervised brushing, chlorhexidine mouthwash, and clotrimazole mouth-paint. Severity of mucositis was graded using WHO grading and pain was assessed by Wong-Baker FACES Pain Rating Scale. RESULTS Sixty four courses of HDMTX were analyzed. The overall incidence of mucositis in the glutamine group was comparable to the SOHP group (71.8% vs 81.2%; P = 0.08). The glutamine group had a significantly lesser incidence of severe mucositis [3.1% vs 44%; RR (95% CI) 0.07 (0.01, 0.35); P < 0.001], shorter overall duration of mucositis [2 (0, 3) days vs 5 (3, 5) days, P < 0.001] and lower median (IQR) pain scores [4.5 (0, 6) Vs 8 (5.25, 8), P < 0.001]. CONCLUSION Glutamine mouthwash is effective in reducing the incidence of severe mucositis and overall duration of mucositis and associated pain in children receiving HDMTX.
Collapse
Affiliation(s)
- S Siva Sankaran
- Department of Pediatrics, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi, 110095, India
| | - Pooja Dewan
- Department of Pediatrics, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi, 110095, India.
| | - Rajeev Kumar Malhotra
- Delhi Cancer Registry Dr. BRA IRCH, All India Institute of Medical Sciences, New Delhi, India
| | - Deepika Harit
- Department of Pediatrics, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi, 110095, India
| | - Bineeta Kashyap
- Department of Microbiology, Dilshad Garden, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, India
| | - Mukesh Yadav
- Department of Pediatrics, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi, 110095, India
| | - Mandeep Singh Khalsa
- Division of Pediatric Hematology-Oncology, Department of Pediatrics, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi, India
| |
Collapse
|
|
2
|
Liu JJ, Sun YM, Xu Y, Mei HW, Guo W, Li ZL. Pathophysiological consequences and treatment strategy of obstructive jaundice. World J Gastrointest Surg 2023; 15:1262-1276. [PMID: 37555128 PMCID: PMC10405123 DOI: 10.4240/wjgs.v15.i7.1262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/29/2023] [Accepted: 05/31/2023] [Indexed: 07/21/2023] Open
Abstract
Obstructive jaundice (OJ) is a common problem in daily clinical practice. However, completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management. The effects of OJ are widespread, affecting the biliary tree, hepatic cells, liver function, and causing systemic complications. The lack of bile in the intestine, destruction of the intestinal mucosal barrier, and increased absorption of endotoxins can lead to endotoxemia, production of proinflammatory cytokines, and induce systemic inflammatory response syndrome, ultimately leading to multiple organ dysfunction syndrome. Proper management of OJ includes adequate water supply and electrolyte replacement, nutritional support, preventive antibiotics, pain relief, and itching relief. The surgical treatment of OJ depends on the cause, location, and severity of the obstruction. Biliary drainage, surgery, and endoscopic intervention are potential treatment options depending on the patient's condition. In addition to modern medical treatments, Traditional Chinese medicine may offer therapeutic benefits for OJ. A comprehensive search was conducted on PubMed for relevant articles published up to August 1970. This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.
Collapse
Affiliation(s)
- Jun-Jian Liu
- Department of Hepatobiliary and Pancreatic Surgery, Tianjin Medical University Nankai Hospital, Tianjin 300102, China
| | - Yi-Meng Sun
- Graduate School, Tianjin Medical University, Tianjin 300070, China
| | - Yan Xu
- Graduate School, Tianjin Medical University, Tianjin 300070, China
| | - Han-Wei Mei
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Wu Guo
- Graduate School, Tianjin Medical University, Tianjin 300070, China
| | - Zhong-Lian Li
- Department of Hepatobiliary and Pancreatic Surgery, Tianjin Medical University Nankai Hospital, Tianjin 300102, China
| |
Collapse
|
|
3
|
Liu JJ, Xu Y, Chen S, Hao CF, Liang J, Li ZL. The mechanism of Yinchenhao decoction in treating obstructive-jaundice-induced liver injury based on Nrf2 signaling pathway. World J Gastroenterol 2022; 28:4635-4648. [PMID: 36157920 PMCID: PMC9476870 DOI: 10.3748/wjg.v28.i32.4635] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 06/08/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Obstructive jaundice (OJ) is caused by bile excretion disorder after partial or complete bile duct obstruction. It may cause liver injury through various mechanisms. Traditional Chinese medicine (TCM) has a lot of advantages in treating OJ. The recovery of liver function can be accelerated by combining Chinese medicine treatment with existing clinical practice. Yinchenhao decoction (YCHD), a TCM formula, has been used to treat jaundice. Although much progress has been made in recent years in understanding the mechanism of YCHD in treating OJ-induced liver injury, it is still not clear. AIM To investigate chemical components of YCHD that are effective in the treatment of OJ and predict the mechanism of YCHD. METHODS The active components and putative targets of YCHD were predicted using a network pharmacology approach. Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes path enrichment analysis were carried out by cluster profile. We predicted the biological processes, possible targets, and associated signaling pathways that YCHD may involve in the treatment of OJ. Thirty male Sprague-Dawley rats were randomly divided into three groups, each consisting of 10 rats: the sham group (Group S), the OJ model group (Group M), and the YCHD-treated group (Group Y). The sham group only received laparotomy. The OJ model was established by ligating the common bile duct twice in Groups M and Y. For 1 wk, rats in Group Y were given a gavage of YCHD (3.6 mL/kg) twice daily, whereas rats in Groups S and M were given the same amount of physiological saline after intragastric administration daily. After 7 d, all rats were killed, and the liver and blood samples were collected for histopathological and biochemical examinations. Total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), and aspartate transaminase (AST) levels in the blood samples were detected. The gene expression levels of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and the nucleus positive rate of NF-E2 related factor 2 (Nrf2) protein were measured. Western blot analyses were used to detect the protein and gene expression levels of Nrf2, Kelch-like ECH-associated protein 1, NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione-S-transferase (GST) in the liver tissues. One-way analysis of variance was used to evaluate the statistical differences using the statistical package for the social sciences 23.0 software. Intergroup comparisons were followed by the least significant difference test and Dunnett's test. RESULTS The effects of YCHD on OJ involve biological processes such as DNA transcription factor binding, RNA polymerase II specific regulation, DNA binding transcriptional activator activity, and nuclear receptor activity. The protective effects of YCHD against OJ were closely related to 20 pathways, including the hepatitis-B, the mitogen-activated protein kinase, the phosphatidylinositol 3-kinase/protein kinase B, and tumor necrosis factor signaling pathways. YCHD alleviated the swelling and necrosis of hepatocytes. Following YCHD treatment, the serum levels of TBIL (176.39 ± 17.03 μmol/L vs 132.23 ± 13.88 μmol/L, P < 0.01), DBIL (141.41 ± 14.66 μmol/L vs 106.43 ± 10.88 μmol/L, P < 0.01), ALT (332.07 ± 34.34 U/L vs 269.97 ± 24.78 U/L, P < 0.05), and AST (411.44 ± 47.64 U/L vs 305.47 ± 29.36 U/L, P < 0.01) decreased. YCHD promoted the translocation of Nrf2 into the nucleus (12.78 ± 0.99 % vs 60.77 ± 1.90 %, P < 0.001). After YCHD treatment, we found a decrease in iNOS (0.30 ± 0.02 vs 0.20 ± 0.02, P < 0.001) and an increase in eNOS (0.18 ± 0.02 vs 0.32 ± 0.02, P < 0.001). Meanwhile, in OJ rats, YCHD increased the expressions of Nrf2 (0.57 ± 0.03 vs 1.18 ± 0.10, P < 0.001), NQO1 (0.13 ± 0.09 vs 1.19 ± 0.07, P < 0.001), and GST (0.12 ± 0.02 vs 0.50 ± 0.05, P < 0.001), implying that the potential mechanism of YCHD against OJ-induced liver injury was the upregulation of the Nrf2 signaling pathway. CONCLUSION OJ-induced liver injury is associated with the Nrf2 signaling pathway. YCHD can reduce liver injury and oxidative damage by upregulating the Nrf2 pathway.
Collapse
Affiliation(s)
- Jun-Jian Liu
- The Second Department of Hepatobiliary and Pancreatic Surgery, Tianjin Medical University NanKai Hospital, Tianjin 300102, China
| | - Yan Xu
- Graduate School, Tianjin Medical University, Tianjin 3000070, China
| | - Shuai Chen
- Department of Thoracic Surgery, Xuzhou City Hospital of Traditional Chinese Medicine, Xuzhou 221000, Jiangsu Province, China
| | - Cheng-Fei Hao
- The Second Department of Hepatobiliary and Pancreatic Surgery, Tianjin Medical University NanKai Hospital, Tianjin 300102, China
| | - Jing Liang
- School of Foreign Languages, Chengdu University of Traditional Chinese Medicine, Chengdu 610000, Sichuan Province, China
| | - Zhong-Lian Li
- The Second Department of Hepatobiliary and Pancreatic Surgery, Tianjin Medical University NanKai Hospital, Tianjin 300102, China
| |
Collapse
|
|
4
|
Celepli S, Çolak B, Celepli P, Bigat İ, Batur HG, Soysal F, Karakurt S, Hücümenoğlu S, Kismet K, Şahin M. Artichoke for biochemistry, histology, and gene expression in obstructive jaundice. REVISTA DA ASSOCIAÇÃO MÉDICA BRASILEIRA 2022; 68:647-652. [DOI: 10.1590/1806-9282.20220001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 02/27/2022] [Indexed: 11/21/2022]
Affiliation(s)
| | | | | | - İrem Bigat
- TOBB University of Economics & Technology, Turkey
| | | | | | | | | | | | | |
Collapse
|
|
5
|
Atypical immunometabolism and metabolic reprogramming in liver cancer: Deciphering the role of gut microbiome. Adv Cancer Res 2020; 149:171-255. [PMID: 33579424 DOI: 10.1016/bs.acr.2020.10.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Much recent research has delved into understanding the underlying molecular mechanisms of HCC pathogenesis, which has revealed to be heterogenous and complex. Two major hallmarks of HCC include: (i) a hijacked immunometabolism and (ii) a reprogramming in metabolic processes. We posit that the gut microbiota is a third component in an entanglement triangle contributing to HCC progression. Besides metagenomic studies highlighting the diagnostic potential in the gut microbiota profile, recent research is pinpointing the gut microbiota as an instigator, not just a mere bystander, in HCC. In this chapter, we discuss mechanistic insights on atypical immunometabolism and metabolic reprogramming in HCC, including the examination of tumor-associated macrophages and neutrophils, tumor-infiltrating lymphocytes (e.g., T-cell exhaustion, regulatory T-cells, natural killer T-cells), the Warburg effect, rewiring of the tricarboxylic acid cycle, and glutamine addiction. We further discuss the potential involvement of the gut microbiota in these characteristics of hepatocarcinogenesis. An immediate highlight is that microbiota metabolites (e.g., short chain fatty acids, secondary bile acids) can impair anti-tumor responses, which aggravates HCC. Lastly, we describe the rising 'new era' of immunotherapies (e.g., immune checkpoint inhibitors, adoptive T-cell transfer) and discuss for the potential incorporation of gut microbiota targeted therapeutics (e.g., probiotics, fecal microbiota transplantation) to alleviate HCC. Altogether, this chapter invigorates for continuous research to decipher the role of gut microbiome in HCC from its influence on immunometabolism and metabolic reprogramming.
Collapse
|
|
6
|
Perna S, Alalwan TA, Alaali Z, Alnashaba T, Gasparri C, Infantino V, Hammad L, Riva A, Petrangolini G, Allegrini P, Rondanelli M. The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review. Int J Mol Sci 2019; 20:E5232. [PMID: 31652531 PMCID: PMC6834172 DOI: 10.3390/ijms20205232] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 10/16/2019] [Accepted: 10/20/2019] [Indexed: 02/07/2023] Open
Abstract
The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy of glutamine and its effect on gut microbiota. As a result of this review, we have summarized that glutamine could affect gut microbiota via different mechanisms including the reduction in the ratio of Firmicutes to Bacteroidetes, with the activation of NF-κB and PI3K-Akt pathways, reducing the intestinal colonization (Eimeria lesions) and bacterial overgrowth or bacterial translocation, increasing the production of secretory immunoglobulin A (SIgA) and immunoglobulin A+ (IgA+) cells in the intestinal lumen, and decreasing asparagine levels. The potential applications of glutamine on gut microbiota include, but are not limited to, the management of obesity, bacterial translocation and community, cytokines profiles, and the management of side effects during post-chemotherapy and constipation periods. Further studies and reviews are needed regarding the effects of glutamine supplementation on other conditions in humans.
Collapse
Affiliation(s)
- Simone Perna
- Department of Biology, College of Science, University of Bahrain, 32038 Sakhir, Bahrain.
| | - Tariq A Alalwan
- Department of Biology, College of Science, University of Bahrain, 32038 Sakhir, Bahrain.
| | - Zahraa Alaali
- Department of Biology, College of Science, University of Bahrain, 32038 Sakhir, Bahrain.
| | - Tahera Alnashaba
- Department of Biology, College of Science, University of Bahrain, 32038 Sakhir, Bahrain.
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona ''Istituto Santa Margherita'', University of Pavia, Pavia 27100, Italy.
| | - Vittoria Infantino
- Department of Biomedical Science and Human Oncology, University of Bari, Bari 70121, Italy.
| | - Layla Hammad
- Department of Biology, College of Science, University of Bahrain, 32038 Sakhir, Bahrain.
| | - Antonella Riva
- Research and Development Department, Indena SpA, 20139 Milan, Italy.
| | | | - Pietro Allegrini
- Research and Development Department, Indena SpA, 20139 Milan, Italy.
| | - Mariangela Rondanelli
- IRCCS Mondino Foundation, Pavia 27100, Italy.
- Department of Public Health, Experimental and Forensic Medicine, Unit of Human and Clinical Nutrition, University of Pavia, Pavia 27100, Italy.
| |
Collapse
|
|
7
|
Tian X, Zhang Z, Li W. Functional Changes of Paneth Cells in the Intestinal Epithelium of Mice with Obstructive Jaundice and After Internal and External Biliary Drainage. Curr Mol Med 2019; 19:746-757. [PMID: 31429688 DOI: 10.2174/1566524019666190820141331] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 07/21/2019] [Accepted: 07/30/2019] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To investigate the functional changes of Paneth cells in the intestinal epithelium of mice with obstructive jaundice (OJ) and after internal biliary drainage (ID) and external biliary drainage (ED). METHODS The experiment was divided into two stages. First stage: Mice were randomly assigned to two groups: (I) sham operation (SH); (II) OJ. The mice were sacrificed before the operation and on the 1st, 3rd, 5th and 7th day after the operation to collect specimens. Second stage: Mice were randomly assigned to four groups: (I) SH; (II) OJ; (III) OJ and ED; and (IV) OJ and ID. They were reoperated on day 5 for biliary drainage procedure. The specimens were collected on day 10. RESULTS The expressions of lysozyme and cryptdin-4 increased first and then decreased over time in group OJ, and the number of Paneth cells decreased gradually with the extension of OJ time（p<0.05. After the secondary operation on the mice to relieve OJ, the number of Paneth cells and expressions of lysozyme and cryptdin-4 in group ID increased more significantly than those in group ED（p<0.05）. CONCLUSION OJ could cause intestinal Paneth cells to dysfunction in mice. ID was more significant than ED in restoring the function of Paneth cells. It might be one of the mechanisms that make ID superior to ED.
Collapse
Affiliation(s)
- Xiaopeng Tian
- Medical School of Chinese PLA, No. 28, Fuxing Road, Beijing 100853, China.,Department of Gastroenterology, Xingtai People's Hospital, Xingtai, Hebei 054000, China
| | - Zixuan Zhang
- Medical School of Chinese PLA, No. 28, Fuxing Road, Beijing 100853, China
| | - Wen Li
- Medical School of Chinese PLA, No. 28, Fuxing Road, Beijing 100853, China.,Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China
| |
Collapse
|
|
8
|
Narkhede R, Desai G, Pande P. Bacteriobilia in Hepato-Pancreato-Biliary Surgery: an Enemy or a Friend in Disguise? Indian J Surg 2019. [DOI: 10.1007/s12262-019-01933-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
|
|
9
|
Tian X, Zhang Z, Li W. Expression of TLR2 and TLR5 in distal ileum of mice with obstructive jaundice and their role in intestinal mucosal injury. Arch Med Sci 2019; 18:237-250. [PMID: 35154543 PMCID: PMC8826794 DOI: 10.5114/aoms.2019.85648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Accepted: 04/18/2019] [Indexed: 12/04/2022] Open
Abstract
INTRODUCTION The aim was to investigate the expression of TLR2 and TLR5 in the distal ileum of mice with obstructive jaundice (OJ) and their role in intestinal mucosal injury. MATERIAL AND METHODS A total of 100 male C57BL/6J mice were randomly assigned to two groups: (I) sham operation (SH); (II) bile duct ligation (BDL). The mice were respectively sacrificed before operation and on the 1st, 3rd, 5th and 7th days after operation to collect specimens. Various indicators were detected by PCR, immunohistochemistry and other methods. RESULTS TLR2 was increased gradually with the extension of OJ time in the BDL group (p < 0.05). However, the changes in the expression of TLR5 were not obvious at different time points. The amount of Bifidobacteria and Lactobacillus showed downward trends in intestinal tract of the BDL group. Furthermore, the amount of Escherichia coli was increased in intestinal tract of the BDL group. The pathological score of intestinal mucosa and the expression of NF-κB increased gradually in the BDL group with the extension of OJ time. There were positive correlations between the pathological score of intestinal mucosa and expressions of TLR2(r = 0.767, p < 0.05) and NF-κB (r = 0.817, p < 0.05) in BDL group. NF-κB expression was positively correlated with TLR2 expression(r = 0.706, p < 0.05). CONCLUSIONS Disturbance of intestinal flora caused by OJ could increase the expression of NF-κB via up-regulating the expression of TLR2 to activate the downstream signaling pathway, thus aggravated the injury of intestinal mucosa.
Collapse
Affiliation(s)
- Xiaopeng Tian
- Medical School of Chinese PLA, Beijing, China
- Department of Gastroenterology, Xingtai People’s Hospital, Xingtai, Hebei, China
| | | | - Wen Li
- Medical School of Chinese PLA, Beijing, China
- Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing, China
| |
Collapse
|
|
10
|
Unal Y, Tuncal S, Kosmaz K, Kucuk B, Kismet K, Cavusoglu T, Celepli P, Senes M, Yildiz S, Hucumenoglu S. The Effect of Calcium Dobesilate on Liver Damage in Experimental Obstructive Jaundice. J INVEST SURG 2018; 32:238-244. [PMID: 29589984 DOI: 10.1080/08941939.2018.1451936] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose/Aim of the study: Inflammation and oxidative stress are two significant factors affecting the degree of liver damage in obstructive jaundice. The aim of this study was to evaluate the effect of calcium dobesilate (CaDob), an effective antioxidant and anti-inflammatory drug, on damage to liver caused by experimental obstructive jaundice. MATERIALS AND METHODS 30 rats in total were randomly placed into three groups, each group consisting of 10 rats. The sham group (Group 1) only received solely laparotomy. In the control group (Group 2), ligation was applied to the biliary tract and no treatment was implemented. In the CaDob group (Group 3), following ligation of the biliary tract, 100 mg/kg/day CaDob was implemented via an orogastric tube for a 10-day period. Liver tissue and blood samples were taken for histopathological and biochemical examination. RESULTS The CaDob group had significantly lower test values for serum liver functions when compared to the control group. Statistically lower levels of tissue malondialdehyde (MDA) and fluorescent oxidation products (FOP) were detected in the CaDob group, and the CaDob group had significantly higher levels of sulfydryl (SH) than the control group. Histopathological scores in the CaDob group were found out to be statistically less than the scores the control group received (p < 0.05). CONCLUSIONS CaDob treatment repaired the histpatological changes induced by bile duct ligation. The hepatoprotective effects of CaDob can be associated with its antioxidant properties of the drug.
Collapse
Affiliation(s)
- Yilmaz Unal
- a Department of General Surgery , Ankara Education and Research Hospital , Ankara , Turkey
| | - Salih Tuncal
- a Department of General Surgery , Ankara Education and Research Hospital , Ankara , Turkey
| | - Koray Kosmaz
- a Department of General Surgery , Ankara Education and Research Hospital , Ankara , Turkey
| | - Berkay Kucuk
- a Department of General Surgery , Ankara Education and Research Hospital , Ankara , Turkey
| | - Kemal Kismet
- a Department of General Surgery , Ankara Education and Research Hospital , Ankara , Turkey
| | - Turgut Cavusoglu
- a Department of General Surgery , Ankara Education and Research Hospital , Ankara , Turkey
| | - Pinar Celepli
- b Department of Pathology , Ankara Education and Research Hospital , Ankara , Turkey
| | - Mehmet Senes
- c Department of Biochemistry , Ankara Education and Research Hospital , Ankara , Turkey
| | - Selin Yildiz
- c Department of Biochemistry , Ankara Education and Research Hospital , Ankara , Turkey
| | - Sema Hucumenoglu
- b Department of Pathology , Ankara Education and Research Hospital , Ankara , Turkey
| |
Collapse
|
|
11
|
Effect of parenteral glutamine supplementation combined with enteral nutrition on Hsp90 expression and lymphoid organ apoptosis in severely burned rats. Burns 2016; 42:1494-1506. [PMID: 27613477 DOI: 10.1016/j.burns.2016.02.009] [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: 04/05/2015] [Revised: 02/09/2016] [Accepted: 02/11/2016] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The aim of this study is to investigate the effects of parenteral glutamine(GLN) supplementation combined with enteral nutrition (EN) on heat shock protein 90(Hsp90) expression, apoptosis of lymphoid organs and circulating lymphocytes, immunological function and survival in severely burned rats. METHODS Male SD rats were randomly assigned into 4 groups: a sham burn+EN+GLN-free amino acid (AA) group (n=10), a sham burn+EN+GLN group (n=10), a burn+EN+AA group (n=10), and a burn +EN +GLN group (n=10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back was made, the burned rats in two experimental groups (the burn+EN+AA group and the burn+EN +GLN group) were fed with a conventional enteral nutrition solution by oral gavage for 7 days. Simultaneously, the rats in the burn+EN+GLN group were given 0.35g GLN/kg body weight/day once via a tail vein injection for 7 days, whereas those in the burn+EN+AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. The rats in two sham burn control groups (the sham burn+EN+AA group and the sham burn+EN +GLN group) were treated in the same procedure as above, except for burn injury. All rats in each of the four groups were given 175kcal/kg body wt/day. There was isonitrogenous, isovolumic and isocaloric intake among four groups. At the end of the 7th day after nutritional programme were finished, all rats were anesthetized and samples were collected for further analysis. Serum immunoglobulin quantification was conducted by ELISA. Circulating lymphocyte numbers were counted by Coulter LH-750 Analyzer. The percentages and apoptotic ratio of CD4 and CD8T lymphocytes in circulation were determined by flow cytometry (FCM). The neutrophil phagocytosis index (NPI) was examined. The GLN concentrations in plasma, thymus, spleen and skeletal muscle were measured by high performance liquid chromatography (HPLC). The organ index evaluation and TUNEL analysis of thymus and spleen were carried out. The expression of Hsp90 in thymus and spleen was analyzed by western blotting. Moreover, the survival in burned rats was observed. RESULTS The results revealed that parenteral GLN supplementation combined with EN significantly increased the GLN concentrations of plasma and tissues, the serum immunoglobulin content, the circulating lymphocyte number, the CD4/CD8 ratio, the indexes of thymus and spleen, NPI and survival as compared with the burn+EN+AA group (p<0.05). The expression of Hsp90 in thymus and spleen in the burn+EN+GLN group was significantly up-regulated as compared with the burn+EN+AA group (p<0.05). The apoptosis in circulating CD4 and CD8 lymphocytes, thymus and spleen in the burn+EN+GLN group was significantly decreased as compared with the burn+EN+AA group (p<0.05). CONCLUSION The results of this study show that parenteral GLN supplementation combined with EN may increase the GLN concentrations of plasma and tissues, up-regulate the expression of Hsp90, attenuate apoptosis in lymphoid organ and circulating lymphocyte, enhance the immunological function and improve survival in severely burned rats. Clinically, therapeutic efforts at the modulation of the immune dysfunction may contribute to a favorable outcome in severely burned patients.
Collapse
|
|
12
|
Effects of enteral nutrition with parenteral glutamine supplementation on the immunological function in septic rats. Br J Nutr 2015; 113:1712-22. [PMID: 26067806 DOI: 10.1017/s0007114515001099] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
The aim of the present study was to investigate the effects of enteral nutrition (EN) with parenteral glutamine (GLN) supplementation on inflammatory response, lymphatic organ apoptosis, immunological function and survival in septic rats by caecal ligation and puncture (CLP). Male rats were randomly assigned into two experimental groups and two sham CLP control groups (n 10 per group). After CLP or sham CLP model and nutrition programme were completed, the GLN concentrations of plasma and tissues and several indices of immunological function including serum Ig content, circulating lymphocyte number, the CD4:CD8 ratio, the neutrophil phagocytosis index (NPI), the organ index and apoptosis of thymus and spleen, and plasma cytokine levels were determined. Moreover, the survival in septic rats was observed. The results revealed that EN with parenteral GLN supplementation remarkably increased the GLN concentrations of plasma and tissues, serum Ig content, the circulating lymphocyte number, the CD4:CD8 ratio, the indexes of thymus and spleen, NPI and survival compared with the control group (P< 0·05). In contrast, the apoptosis of thymus and spleen and the levels of TNF-α, IL-1β and IL-6 in plasma were obviously decreased compared with the control group (P< 0·05). These results show that EN with parenteral GLN supplementation diminished the release of inflammatory cytokines, attenuated lymphatic organ apoptosis, enhanced the immunological function and improved survival in septic rats.
Collapse
|
|
13
|
Chen J, Dong JT, Li XJ, Gu Y, Cheng ZJ, Cai YK. Glucagon-like peptide-2 protects impaired intestinal mucosal barriers in obstructive jaundice rats. World J Gastroenterol 2015; 21:484-490. [PMID: 25593463 PMCID: PMC4292279 DOI: 10.3748/wjg.v21.i2.484] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2014] [Revised: 07/03/2014] [Accepted: 07/30/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect.
METHODS: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14th day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group.
RESULTS: In the rat model, jaundice was obvious, and the rats’ activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced IgA expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group (P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group (P < 0.01).
CONCLUSION: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal IgA and reduced bilirubin and endotoxin.
Collapse
|
|
14
|
Alecrim HM, Duarte SAC, Amaral MEB, Diógenis F, Carneiro FP, Sousa JBD. Effect of glutamine supplementation on left colon healing in rats with extrahepatic biliary obstruction. Acta Cir Bras 2015; 30:73-9. [DOI: 10.1590/s0102-86502015001000010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 12/30/2014] [Indexed: 11/22/2022] Open
|
|
15
|
Fan J, Li G, Wu L, Tao S, Wang W, Sheng Z, Meng Q. Parenteral glutamine supplementation in combination with enteral nutrition improves intestinal immunity in septic rats. Nutrition 2014; 31:766-74. [PMID: 25837225 DOI: 10.1016/j.nut.2014.11.021] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Revised: 11/15/2014] [Accepted: 11/29/2014] [Indexed: 01/27/2023]
Abstract
OBJECTIVES The gut-associated lymphoid tissue is continuously exposed to antigens in the gut lumen and becomes the first line of defense against enteric bacteria and associated toxin. The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation in combination with enteral nutrition (EN) on intestinal mucosal immunity in septic rats by cecal ligation and puncture (CLP). METHODS Male Sprague-Dawley rats were randomly assigned into four groups: A sham CLP + EN + saline group (n = 10), a sham CLP + EN + GLN group (n = 10), a CLP + EN + saline group (n = 10), and a CLP + EN + GLN group (n = 10). At 2 h after CLP or sham CLP, all rats in each of the four groups received an identical enteral nutrition solution as their base formula. Then, the rats in the sham CLP + EN + GLN group and CLP + EN + GLN group were given 0.35 g GLN/kg body weight daily for 7 d, all at the same time, via a tail vein injection; whereas those in the sham CLP + EN + saline group and CLP + EN + saline group were daily administered isovolumic sterile 0.9% saline for comparison. All rats in each of the four groups were given 290 kcal/kg body wt/d for 7 d. At the end of the seventh day after the nutritional program was finished, all rats were euthanized and the entire intestine was collected. Total Peyer's patches (PP) cell yield was counted by a hemocytometer. The percentage of PP lymphocyte subsets was analyzed by flow cytometry. The number of intestinal lamina propria IgA plasma cells was determined by the immunohistochemistry technique. The intestinal immunoglobulin A (IgA) levels were assessed by ELISA. PP apoptosis was evaluated by terminal deoxyuridine nick-end labeling. RESULTS The results revealed total PP cell yield, the numbers of PP lymphocyte subsets, intestinal lamina propria IgA plasma cells, and intestinal IgA levels in the CLP + EN + GLN group were significantly increased when compared with the CLP + EN + saline group (P < 0.05). On the other hand, the number of TUNEL-stained cells within PPs in the CLP + EN + GLN group was markedly decreased as compared with the CLP + EN + saline group (P < 0.05). CONCLUSION The results of this study show that parenteral glutamine supplementation in combination with enteral nutrition may attenuate PP apoptosis, increase PP cell yield and intestinal lamina propria IgA plasma cells, and subsequently improve intestinal mucosal immunity. Clinically, these results suggest therapeutic efforts at improving intestinal immunity may contribute to the prevention and treatment of sepsis.
Collapse
Affiliation(s)
- Jun Fan
- Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, P.R. China.
| | - Guoping Li
- Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, P.R. China
| | - Lidong Wu
- Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, P.R. China
| | - Shaoyu Tao
- Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, P.R. China
| | - Wei Wang
- Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, P.R. China
| | - Zhiyong Sheng
- Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Jiangxi, P.R. China
| | - Qingyan Meng
- Department of Burns, The Northern Hospital, Liaoning, P.R. China
| |
Collapse
|
|
16
|
Intestinal barrier dysfunction in HIV infection: pathophysiology, clinical implications and potential therapies. Infection 2014; 42:951-9. [PMID: 25070877 DOI: 10.1007/s15010-014-0666-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2014] [Accepted: 07/11/2014] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Current pathogenetic aspects on HIV infection highlight the importance of a chronic immune activation ultimately leading to T lymphocyte homeostasis disruption and immune deregulation associated with disease manifestations and progression. It is widely accepted that this continuous immune activation in HIV infection is principally driven by the phenomenon of pathological microbial translocation (MT). METHODS Review of the literature on the role of intestinal barrier dysfunction in HIV infection, with emphasis on the implicated pathophysiological mechanisms, clinical implications and potentially effective therapeutic interventions. FINDINGS MT in HIV infection is promoted by a multifactorial disruption of all major levels comprising the intestinal barrier defense. Specifically, HIV infection disrupts the integrity of the intestinal biological (quantitative and qualitative alterations of gut microecology, overgrowth of pathogenic bacteria), immune (depletion of CD4(+) T cells, especially Th17 cells, increased CD4+ FoxP3+ Tregs, decreased mucosal macrophages phagocytic capacity, development of intestinal proinflammatory milieu) and mechanical barrier (enterocytes' apoptosis, disruption of tight junctions). Intestinal barrier dysfunction allows the passage of microbes and immunostimulatory bioproducts from the gut lumen first in the lamina propria and thereafter in the systemic circulation, thus continuously promoting a local and systemic inflammatory response. This chronic immune activation is associated with HIV disease progression, suboptimal response to HAART and development of non-AIDS comorbidities. CONCLUSIONS We have reached a point where the effective control of HIV viremia by HAART should be combined with emerging pharmacological approaches aiming at the restoration of the intestinal barrier, targeting its diverse levels of structure and function. Elimination of the MT phenomenon would mitigate its effect on immune homeostasis, which might improve the prognosis of the HIV-infected patient in terms of morbidity and mortality.
Collapse
|
|
17
|
Xu F, Dai CL, Peng SL, Zhao Y, Jia CJ, Xu YQ. Preconditioning with glutamine protects against ischemia/reperfusion-induced hepatic injury in rats with obstructive jaundice. Pharmacology 2014; 93:155-65. [PMID: 24801881 DOI: 10.1159/000360181] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2013] [Accepted: 01/31/2014] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To ascertain whether glutamine (Gln) pretreatment protects rats with obstructive jaundice from hepatic ischemia/reperfusion (I/R) injury and to determine the underlying molecular mechanisms. METHODS An obstructive jaundice rat model was developed by bile duct ligation. On the first day after the operation, all rats were randomized into two groups and received oral Gln or normal saline (NS) daily for 7 days. Then both groups underwent a 15-min liver ischemia via the Pringle maneuver. Blood samples as well as liver and intestinal tissues were harvested and measured after 1, 6 and 24 h of reperfusion. RESULTS The results showed that the histological morphology of the liver and intestinal tissues significantly improved in the Gln group after I/R injury compared with the NS group. Serum proteins and enzymes associated with hepatic function also significantly improved in the Gln group. The level of glutathione increased and the levels of malondialdehyde and myeloperoxidase decreased in the Gln group. The levels of interleukin-1β and tumor necrosis factor-α decreased in the Gln group. Moreover, bcl-2 protein expression was upregulated and intercellular adhesion molecule 1 and bax protein expression downregulated in the Gln group; the caspase 3 mRNA level significantly increased in the Gln group. CONCLUSIONS The study demonstrates that preconditioning with Gln significantly improves hepatic structure and function after I/R injury in rats with obstructive jaundice. The protective effect of Gln was mediated by the inhibition of reactive oxygen species and inflammation as well as a reduction in hepatocyte apoptosis.
Collapse
Affiliation(s)
- Feng Xu
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital, China Medical University, Shenyang, China
| | | | | | | | | | | |
Collapse
|
|
18
|
Zuhl MN, Lanphere KR, Kravitz L, Mermier CM, Schneider S, Dokladny K, Moseley PL. Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression. J Appl Physiol (1985) 2014; 116:183-91. [PMID: 24285149 PMCID: PMC3921361 DOI: 10.1152/japplphysiol.00646.2013] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 11/25/2013] [Indexed: 11/22/2022] Open
Abstract
The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P < 0.05). IκBα expression in peripheral blood mononuclear cells was higher 240 min after exercise in the GLN trial compared with the PLA trial (1.411 ± 0.523 vs. 0.9839 ± 0.343, respectively; P < 0.05). In vitro using the intestinal epithelial cell line Caco-2, we measured effects of GLN supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P < 0.05). Occludin levels increased after 4 mM supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P < 0.001). GLN supplementation prevented exercise-induced permeability, possibly through HSF-1 activation.
Collapse
Affiliation(s)
- Micah N Zuhl
- Department of Health, Exercise, and Sport Science, University of New Mexico, Albuquerque, New Mexico
| | | | | | | | | | | | | |
Collapse
|
|
19
|
Hatipoğlu AR, Oğuz S, Gürcan S, Yalta T, Albayrak D, Erenoğlu C, Sağıroğlu T, Sezer YA. Combined effects of tauroursodeoxycholic Acid and glutamine on bacterial translocation in obstructive jaundiced rats:. Balkan Med J 2013; 30:362-8. [PMID: 25207142 DOI: 10.5152/balkanmedj.2013.7785] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Accepted: 09/09/2013] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Bacterial Translocation is believed to be an important factor on mortality and morbidity in Obstructive Jaundiced. AIMS We investigated the probable or estimated positive effects of tauroursodeoxycholic acid, which has antibacterial and regulatory effects on intestinal flora, together with glutamine on BT in an experimental obstructive jaundiced rat model. STUDY DESIGN Animal experimentation. METHODS Forty adult, male, Sprague Dawley rats were used in this study. Animals were randomised and divided into five groups of eight each: sham (Sh); control (common bile duct ligation, CBDL); and supplementation groups administered tauroursodeoxycholic acid (CBDL+T), glutamine (CBDL+G), or tauroursodeoxycholic acid plus glutamine (CBDL+TG). Blood and liver, spleen, MLN, and ileal samples were taken via laparotomy under sterile conditions for investigation of bacterial translocation and intestinal mucosal integrity and hepatic function tests on the tenth postoperative day. RESULTS There were statistically significant differences in BT rates in all samples except the spleen of the CBDL+TG group compared with the CBDL group (p=0.041, p=0.026, and p=0.041, respectively). CONCLUSION It is essential to protect hepatic functions besides maintaining intestinal mucosal integrity in the active struggle against BT occurring in obstructive jaundice. The positive effect on intestinal mucosal integrity can be increased if glutamine is used with tauroursodeoxycholic acid, which also has hepatoprotective and immunomodulatory features.
Collapse
Affiliation(s)
- Ahmet Rahmi Hatipoğlu
- Department of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey
| | - Serhat Oğuz
- Department of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey
| | - Saban Gürcan
- Department of Microbiology, Trakya University Faculty of Medicine, Edirne, Turkey
| | - Tülin Yalta
- Department of Pathology, Trakya University Faculty of Medicine, Edirne, Turkey
| | - Doğan Albayrak
- Department of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey
| | - Cengiz Erenoğlu
- Department of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey
| | - Tamer Sağıroğlu
- Department of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey
| | - Yavuz Atakan Sezer
- Department of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey
| |
Collapse
|
|
20
|
Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, Karatza E, Zisimopoulos D, Maroulis I, Kontogeorgou E, Georgiou CD, Scopa CD, Thomopoulos KC. Intestinal mucosal proliferation, apoptosis and oxidative stress in patients with liver cirrhosis. Ann Hepatol 2013; 12:301-307. [PMID: 23396742 DOI: 10.1016/s1665-2681(19)31369-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/01/2023]
Abstract
BACKGROUND Intestinal mucosal barrier dysfunction in liver cirrhosis and its implicated mechanisms is of great clinical importance because it is associated with the development of serious complications from diverse organs through promotion of systemic endotoxemia. AIM The present study was designed to investigate whether enterocytes' proliferation, apoptosis and intestinal oxidative stress are altered in the intestinal mucosa of patients with compensated and decompensated liver cirrhosis. MATERIAL AND METHODS Twelve healthy controls (group A) and twenty four cirrhotic patients at a compensated (n = 12, group B) or decompensated condition (n = 12, group C) were subjected to duodenal biopsy. In intestinal specimens mucosal apoptotic and mitotic activity and their ratio were recorded by means of morphological assessment and mucosal lipid hydroperoxides were measured. Plasma endotoxin concentration, an index of gut barrier function, was also determined. RESULTS Cirrhotic patients presented significantly higher serum endotoxin concentrations as compared to healthy controls (P < 0.001), whilst endotoxemia was higher in decompensated disease (P < 0.05 vs. compensated cirrhosis). Intestinal mucosal mitotic count was significantly lower in patients with compensated and decompensated cirrhosis compared to controls (P < 0.01, respectively), whilst a trend towards increased apoptosis was recorded. The mitotic/apoptotic ratio was significantly reduced in groups B (P < 0.05) and C (P < 0.01) as compared to controls. Intestinal lipid peroxidation was significantly increased in decompensated cirrhotics (P < 0.001 vs. groups A and B). CONCLUSIONS The present study demonstrates for the first time that human liver cirrhosis is associated with decreased intestinal mucosal proliferation and proliferation/apoptosis ratio even at early stages of cirrhosis and increased intestinal oxidative stress in advanced liver disease.
Collapse
|
|
21
|
Turkez H, Geyikoglu F, Yousef MI, Celik K, Bakir TO. Ameliorative effect of supplementation with L-glutamine on oxidative stress, DNA damage, cell viability and hepatotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat hepatocyte cultures. Cytotechnology 2012; 64:687-99. [PMID: 22453904 PMCID: PMC3488374 DOI: 10.1007/s10616-012-9449-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Accepted: 03/05/2012] [Indexed: 12/11/2022] Open
Abstract
The most potent of the dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is a persistent and ubiquitous environmental contaminant. And the health impact of exposure to TCDD is of great concern to the general public. Recent data indicate that L-glutamine (Gln) has antioxidant properties and may influence hepatotoxicity. The objective of the present study was undertaken to explore the effectiveness of Gln in alleviating the hepatotoxicity of TCDD on primary cultured rat hepatocytes. Gln (0.5, 1 and 2 mM) was added to cultures alone or simultaneously with TCDD (0.005 and 0.01 mM). The hepatocytes were treated with TCDD and Gln for 48 h. Then cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC), total glutathione (TGSH) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. The DNA damage was also analyzed by liver micronucleus assay (MN) and 8-oxo-2-deoxyguanosine (8-OH-dG). The results of MTT and LDH assays showed that TCDD decreased cell viability but not L-glutamine. TCDD also increased TOS level in rat hepatocytes and significantly decreased TAC and TGSH levels. On the basis of increasing doses, the dioxin in a dose-dependent manner caused significant increases of micronucleated hepatocytes (MNHEPs) and 8-OH-dG as compared to control culture. Whereas, in cultures exposured with Gln alone, TOS levels were not changed and TAC and TGSH together were significantly increased in dose-dependent fashion. The presence of Gln with TCDD modulated the hepatotoxic effects of TCDD on primary hepatocytes cultures. Noteworthy, Gln has a protective effect against TCDD-mediated DNA damages. As conclusion, we reported here an increased potential therapeutic significance of L-glutamine in TCDD-mediated hepatic injury for the first time.
Collapse
Affiliation(s)
- Hasan Turkez
- Department of Molecular Biology and Genetics, Faculty of Sciences, Erzurum Technical University, Erzurum, Turkey
| | - Fatime Geyikoglu
- Department of Biology, Faculty of Sciences, Atatürk University, 25240 Erzurum, Turkey
| | - Mokhtar I. Yousef
- Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21526 Egypt
| | - Kubra Celik
- Department of Biology, Faculty of Sciences, Atatürk University, 25240 Erzurum, Turkey
| | - Tulay O. Bakir
- Department of Biology, Faculty of Sciences, Atatürk University, 25240 Erzurum, Turkey
| |
Collapse
|
|
22
|
Abstract
BACKGROUND Two novel antiendotoxin peptides, P6 and C1, may reduce the inflammatory response. This study aimed to determine the effect of endotoxin on hepatic cytokine response and to assess P6 and C1-related attenuation of the proinflammatory response to endotoxemia, in experimental biliary obstruction. MATERIALS AND METHODS 15 Male Wistar rats were randomized to one of three groups: bile duct ligation (BDL)+P6 (n=5), BDL+C1 (n=5), and BDL+no peptide (n=5). Rats were weighed and underwent BDL surgery on day 1. On day 8, the rats were reweighed and isolated hepatic perfusion was carried out. P6 or C1 peptide (10 μmol/l) was preincubated with 300 ml of endotoxin-containing Krebs perfusate. After perfusion of 10 min with endotoxin-free perfusate, the livers were perfused for another 10 min with 300 ml of perfusate-containing endotoxin on its own or endotoxin plus peptide. This was followed by a further 100 min of perfusion with endotoxin-free perfusate. Effluent perfusate was collected at 20-min intervals for subsequent biochemical and cytokine analyses. RESULTS Perfusion with endotoxin+P6 or endotoxin+C1 resulted in no significant difference in weight loss, or interleukin-6 response compared with perfusion with endotoxin alone. However, perfusion with endotoxin+P6 or endotoxin+C1 significantly reduced the tumor necrosis factor-α response to portal endotoxemia compared with perfusion with endotoxin alone. CONCLUSION This study demonstrates that novel antiendotoxin peptides may attenuate the hepatic inflammatory response in portal endotoxemia. In obstructive jaundice, preoperative peptide administration may reduce endotoxin-related postoperative complications.
Collapse
|
|
23
|
Türkez H, Geyikoğlu F, Yousef MI. Modulatory effect of l-glutamine on 2,3,7,8 tetrachlorodibenzo-p-dioxin-induced liver injury in rats. Toxicol Ind Health 2011; 28:663-72. [DOI: 10.1177/0748233711420474] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The aim of this study was to explore the effectiveness of l-glutamine (Gln) in alleviating the toxicity of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) in liver of rats. Rats were intraperitoneally administered Gln and TCDD doses daily for 21 days. In the liver of rats, the biochemical tests, pathological examination and micronucleus (MN) test were performed. TCDD significantly decreased the activities of antioxidant enzymes and serious pathological findings. Moreover, the rate of MNs in hepatocytes increased after treatment with dioxin. In rats treated with Gln alone, the MNs remained unchanged, but the ratio of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px) were significantly increased. Gln also prevented the suppression of GSH-Px (except for superoxide dismutase and catalase) and GSH in the livers of animals exposed to TCDD and displayed a strong protective effect against MNs. Thus, our findings for Gln might provide new insight into the development of therapeutic and preventive approaches in TCDD toxicity.
Collapse
Affiliation(s)
- Hasan Türkez
- Department of Biology, Atatürk University, Erzurum, Turkey
| | | | - Mokhtar I Yousef
- Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
24
|
Cao Y, Zhao C, Xu F, Dai CL. Interleukin-10 suppresses hepatic TGF-β1 expression and attenuates hepatocyte apoptosis in biliary-obstructed rats. Shijie Huaren Xiaohua Zazhi 2011; 19:1773-1779. [DOI: 10.11569/wcjd.v19.i17.1773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the effect of interleukin-10 (IL-10) on hepatocyte apoptosis in biliary-obstructed rats.
METHODS: Male Wistar rats were divided randomly into sham operation (SO) group, obstructive jaundice (OJ) group and IL-10 group. Rats of the OJ and IL-10 groups underwent ligation and severing of the common bile duct, while mobilization of the common bile duct was performed in the SO group. The IL-10 group was intraperitoneally injected with IL-10 (4 μg/kg) daily after operation. The mRNA and protein expression of transforming growth factor-β1 (TGF-β1) in liver tissue was detected by fluorescence real-time quantitative PCR and immunohistochemical staining, respectively. Blood samples were taken to measure serum total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, while hepatic cell apoptosis was evaluated by TUNEL method.
RESULTS: Compared to the SO group, the levels of serum ALT and AST, hepatic TGF-β1 mRNA and protein expression, and hepatic cell apoptosis index significantly increased in the OJ group 3 days after operation (ALT: 91.83 U/L ± 21.47 U/L vs 47.67 U/L ± 12.79 U/L; AST: 208.67 U/L ± 32.36 U/L vs 75.17 U/L ± 11.96 U/L; TGF-β1 mRNA: 7.48 ± 1.51 vs 1.21 ± 0.79; TGF-β1 protein: 6.11% ± 1.11% vs 1.26% ± 0.64%; apoptosis: 15.06% ± 1.17% vs 3.94% ± 0.46%; all P < 0.05), and further increased 7 d after operation (ALT: 178.83 U/L ± 46.25 U/L vs 44.50 U/L ± 9.97 U/L; AST: 461.17 U/L ± 88.48 U/L vs 76.50 U/L ± 12.39 U/L; TGF-β1 mRNA: 11.98 ± 3.05 vs 1.01 ± 0.52; TGF-β1 protein: 9.97% ± 2.84% vs 1.68% ± 0.71%; apoptosis: 23.49% ± 3.35% vs 4.31% ± 0.67%; all P < 0.05). Treatment with IL-10 significantly decreased hepatic function, hepatic TGF-β1 expression, and hepatic cell apoptosis compared to the OJ group 7 d after operation (ALT: 94.17 U/L ± 20.02 U/L vs 178.83 U/L ± 46.25 U/L; AST: 257.83 U/L ± 56.53 U/L vs 461.17 U/L ± 88.48 U/L; TGF-β1 mRNA: 7.05 ± 1.15 vs 11.98 ± 3.05; TGF-β1 protein: 7.06% ± 1.32% vs 9.97% ± 2.84%; apoptosis: 15.08% ± 1.69% vs 23.49% ± 3.35%; all P < 0.05).
CONCLUSION: IL-10 could attenuate hepatocyte apoptosis by suppressing hepatic TGF-β1 expression in biliary-obstructed rats.
Collapse
|
|
25
|
dos Santos RDGC, Viana ML, Generoso SV, Arantes RE, Davisson Correia MIT, Cardoso VN. Glutamine supplementation decreases intestinal permeability and preserves gut mucosa integrity in an experimental mouse model. JPEN J Parenter Enteral Nutr 2011; 34:408-13. [PMID: 20631386 DOI: 10.1177/0148607110362530] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Glutamine (GLN) is the preferred fuel for enterocytes, and GLN supplementation is critical during stressful conditions. The aim of this study was to evaluate the effect of GLN on intestinal barrier permeability and bacterial translocation in a murine experimental model. METHODS Swiss male mice (25-30 g) were randomized into 3 groups: (1) sham group; (2) intestinal obstruction (IO) group; (3) IO and GLN (500 mg/kg/d) group. Two different experiments were carried out to assess intestinal permeability and bacterial translocation. In the first experiment, the animals were divided into the 3 groups described above and received diethylenetriamine pentaacetate radiolabeled with technetium ((99m)Tc) on the eighth day. At different time points after intestinal obstruction, blood was collected to determine radioactivity. The animals were killed, and the small intestine was removed for histological analyses. In the bacterial translocation study, on the eighth day all groups received Escherichia coli labeled with (99m)Tc. After 90 minutes, the animals underwent intestinal obstruction and were killed 18 hours later. Blood, mesenteric lymph nodes, liver, spleen, and lungs were removed to determine radioactivity. Statistical significance was considered when P < or = .05. RESULTS The levels of intestinal permeability and bacterial translocation were higher in the IO group than in the sham and GLN groups (P < .05). GLN decreased intestinal permeability and bacterial translocation to physiologic levels in the treated animals and preserved intestinal barrier integrity. CONCLUSIONS GLN had a positive impact on the intestinal barrier by reducing permeability and bacterial translocation to physiologic levels and preserving mucosal integrity.
Collapse
|
|
26
|
Karatepe O, Acet E, Battal M, Adas G, Kemik A, Altiok M, Kamali G, Koculu S, Cagatay A, Kamali S, Karahan S. Effects of glutamine and curcumin on bacterial translocation in jaundiced rats. World J Gastroenterol 2010; 16:4313-20. [PMID: 20818815 PMCID: PMC2937112 DOI: 10.3748/wjg.v16.i34.4313] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of curcumin on bacterial translocation and oxidative damage in an obstructive jaundice model and compare the results to glutamine, an agent known to be effective and clinically used.
METHODS: Twenty-four female Wistar-Albino rats, weighing 200-250 g, were randomly divided into three groups (8 in each group). After ligation of the common bile duct in all animals, Group I received oral normal saline, Group II received oral glutamine and Group III received oral curcumin for seven days. Blood samples via cardiac puncture, tissue samples (terminal ileum, liver and mesenteric lymph node) and peritoneal fluid were obtained from the animals at the time of death to investigate bacterial translocation and oxidative damage.
RESULTS: We observed that both glutamine and curcumin reduced bacterial translocation in blood, hepatocellular damage, plasma cytokine levels, oxidative tissue damage and apoptosis significantly compared to the control group. Additionally, glutamine showed protective effects on ileal epithelium and reduced villus atrophy.
CONCLUSION: On the basis of these findings, both curcumin and glutamine are thought to be effective in preventing or reducing bacterial translocation and oxidative damage in obstructive jaundice.
Collapse
|
|
27
|
Paiva Neto MCD, Almeida REF, Xavier MM, Takano GHS, Silva Jr ODCE, Cruz CATD, Sousa JBD. Influence of glutamine on morphological and functional changes of liver in the presence of extrahepatic biliary obstruction in rats. Acta Cir Bras 2010. [DOI: 10.1590/s0102-86502010000400014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
PURPOSE: To study the influence of glutamine on functional and morphological changes of liver in the extrahepatic biliary obstruction through an experimental model in rats. METHODS: Seventy Wistar rats were divided into four groups: control (group C) fictitious operation, (group FO), submitted to laparotomy with handling of bile ducts, but without hepatic duct ligation, (group EBO) submitted to laparotomy and hepatic duct ligation, one of them submitted to supplementation with glutamine 2% (group G). The control group consisted of 6 animals. The animals from groups FO, EBO and G were divided into three groups consisting of 6 animals each, being sacrificed at 7, 14 and 21 days after operation, respectively. Blood samples were collected for biochemical analysis and a fragment of liver tissue was collected from the middle lobe for histological analysis. RESULTS: Both for biochemical analysis (BT, aspartate and alanine aminotransferase AST, ALT and alkaline phosphatase FAL) and for histopathological changes (fibrosis, portal inflammation, parenchymal inflammation, hepatocytic changes and duct proliferation), no statistical difference between groups submitted to extrahepatic biliary obstruction (EBO) with and without treatment with glutamine (G) was observed. CONCLUSION: Glutamine supplementation did not alter the prognosis of liver enzymes and histopathological changes in animals submitted to extrahepatic biliary obstruction.
Collapse
|
|
28
|
Fasina YO, Bowers JB, Hess JB, McKee SR. Effect of dietary glutamine supplementation on Salmonella colonization in the ceca of young broiler chicks. Poult Sci 2010; 89:1042-8. [PMID: 20371858 DOI: 10.3382/ps.2009-00415] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Live poultry is an important vehicle for transmitting Salmonella Typhimurium to humans that have salmonellosis. It is therefore imperative to reduce Salmonella Typhimurium levels in the gastrointestinal tract of live chickens. Glutamine is an established immunonutrient that is capable of alleviating disease conditions in humans and rats. Thus, 2 experiments that used Ross broiler chicks were conducted to evaluate the effect of glutamine supplementation at 1% level of the diet on cecal Salmonella Typhimurium levels in young broiler chicks. Experiment 1 consisted of i) treatment 1 (control, CN), in which chicks were given an unmedicated corn-soybean meal basal starter diet without glutamine supplementation or Salmonella Typhimurium challenge; ii) treatment 2 (CST), in which chicks were given the same diet as CN but challenged with 3.6 x 10(6) cfu Salmonella Typhimurium/mL at 3 d of age; and iii) treatment 3 (GST), in which chicks were given the unmedicated corn-soybean meal basal starter diet supplemented with glutamine at 1% level, and challenged with 3.6 x 10(6) cfu at 3 d of age. Experiment 2 used similar treatments (CN, CST, and GST), except that chicks in CST and GST were challenged with 7.4 x 10(7) cfu Salmonella Typhimurium/mL, and a fourth treatment was added. The fourth treatment consisted of chicks that were not challenged with Salmonella Typhimurium but given the same diet as in GST. Duration of each experiment was 14 d. Growth performance of chicks was monitored weekly, and cecal Salmonella Typhimurium concentration was microbiologically enumerated on d 4, 10, or 11 postchallenge. Results showed that glutamine supplementation improved BW and BW gain in experiment 2 (P < 0.05) but did not reduce cecal Salmonella Typhimurium levels in either experiment (P > 0.05). The optimum supplemental level of glutamine that will enhance intestinal resistance to Salmonella Typhimurium colonization should be determined.
Collapse
Affiliation(s)
- Y O Fasina
- Department of Poultry Science, Auburn University, 260 Lem Morrison Drive, Auburn, AL 36849-5416, USA.
| | | | | | | |
Collapse
|
|
29
|
Wang Y, Tao YX, Cai W, Tang QY, Feng Y, Wu J. Protective effect of parenteral glutamine supplementation on hepatic function in very low birth weight infants. Clin Nutr 2010; 29:307-11. [PMID: 20416995 DOI: 10.1016/j.clnu.2010.03.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2009] [Revised: 03/08/2010] [Accepted: 03/11/2010] [Indexed: 11/16/2022]
Abstract
BACKGROUND & AIMS Hepatic dysfunction is one of the most frequent complications of parenteral nutrition. Very low birth weight (VLBW) infants are more sensitive to liver injury due to physiological immaturity. Our studies in animals showed that glutamine supplementation could attenuate TPN-associated liver injury. The aim of study was to investigate whether parenteral glutamine supplementation can improve hepatic tolerance in VLBW infants. METHODS We performed a double-blind, randomized, and controlled clinical study to investigate whether parenteral glutamine supplementation can improve hepatic tolerance in VLBW infants. Thirty VLBW infants at two children's centers were randomly assigned to either a control group or a glutamine-supplemented group. The primary endpoints were hepatic function and mortality. The secondary endpoints were the time to achieve full enteral nutrition, episodes of gastric residuals, duration of parenteral nutrition, weight and head circumference gain, length of hospitalization, and days on ventilator. RESULTS The serum levels of aspartate aminotransferase (AST) and total bilirubin (Tbi) were decreased after PN in the glutamine-supplemented group (P < 0.05). No deaths occurred in this study. Four infants assigned to the control group and two infants in the glutamine-supplemented group were withdrawn from the study, according to intention to treat: relative risk [RR]: 1.182; 95% confidence interval [CI]: 0.937-1.490. CONCLUSIONS Parenteral glutamine supplementation can improve hepatic tolerance in very low birth weight infant, suggesting a hepato-protective effect.
Collapse
Affiliation(s)
- Ying Wang
- Clinical Nutrition Center, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, PR China
| | | | | | | | | | | |
Collapse
|
|
30
|
Protection of Salvia miltiorrhizae to the spleen and thymus of rats with severe acute pancreatitis or obstructive jaundice. Mediators Inflamm 2009; 2009:186136. [PMID: 20016826 PMCID: PMC2790077 DOI: 10.1155/2009/186136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2009] [Accepted: 08/31/2009] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE To investigate the therapeutic effects and mechanism of Salvia miltiorrhizae in the treatment of SAP and OJ. METHODS A total of 288 rats were used for SAP- and OJ-associated experiments. The rats were randomly divided into sham-operated group, model control group and treated group. The mortality rates of rats, contents of endotoxin and PLA(2) in blood, pathological changes of different indexes in spleen and thymus were observed. RESULTS The contents of endotoxin and PLA2 in treated group were significantly lower than those in model control group.The pathological severity scores of spleen and thymus of SAP rats as well as that of spleen of OJ rats in treated groups were significantly lower than those in model control groups (P < .05). The staining intensity as well as the product of the staining intensity and positive rate of Bax protein of spleen in model control group were significantly higher than those in treated groups (P < .01) , and the apoptosis index of spleen in treated group was significantly lower than that in model control group (P < .01). CONCLUSION Salvia miltiorrhizae exerts protective effects on the spleen and thymus of SAP rats and spleen of OJ rats.
Collapse
|
|
31
|
Zhang M, Wang XQ, Zhou YK, Ma YL, Shen TY, Chen HQ, Chu ZX, Qin HL. Effects of oral Lactobacillus plantarum on hepatocyte tight junction structure and function in rats with obstructive jaundice. Mol Biol Rep 2009; 37:2989-99. [PMID: 19816788 DOI: 10.1007/s11033-009-9866-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2009] [Accepted: 09/29/2009] [Indexed: 01/16/2023]
Abstract
Surgery and infection are prominent risk factors for the development of obstructive cholestasis which in turn is associated with failure of the liver barrier. We studied the effects of oral Lactobacillus plantarum (LP) supplementation on endotoxemia, oxidative stress, apoptosis, and tight junctions of hepatocytes in an experimental model of obstructive jaundice. Fifty male Wistar rats were randomly divided into five groups of 10 each: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BLD followed by oral LP treatment; group IV, BDL followed by internal biliary drainage (IBD); group V, BDL followed by IBD and oral LP treatment. Hepatocyte apoptosis, plasma reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, and portal blood endotoxin levels were measured and changes in tight junction-associated proteins occludin, claudin-1, claudin-4, and ZO-1 were observed. Compared to the sham-operated group I, significant increases in endotoxemia, apoptosis, and GSSG were observed in group II and significant decreases were observed in group V. Tight junctions were destroyed in group II animals but were not in animals treated with oral LP (groups III and V). An increase in occludin, claudin-1, claudin-4, and ZO-1 mRNA and protein levels were detected in livers in LP-treated animals (group V) compared with group II levels. Oral LP treatment of rats with obstructive jaundice assisted in the return of active hepatic barrier function. These results may lead to treatments to prevent the deleterious effects of obstructive jaundice.
Collapse
Affiliation(s)
- Ming Zhang
- Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yishan Road, 200233 Shanghai, China
| | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Protective effects of Salvia miltiorrhizae on multiple organs of rats with obstructive jaundice. Mediators Inflamm 2009; 2009:602935. [PMID: 19672457 PMCID: PMC2722062 DOI: 10.1155/2009/602935] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2009] [Accepted: 06/10/2009] [Indexed: 01/08/2023] Open
Abstract
PURPOSE we aim to explore the protective effects of Salvia miltiorrhizae injection on multiple organs of obstructive jaundice (OJ) rats through observing the impact of this injection on the pathological alterations in these organs and the contents of endotoxin, PLA(2), and TNF-alpha in the blood. METHODS A total of 90 mice were randomly divided into sham-operated group, model-control group, and Salvia miltiorrhizae-treated group (n = 30). According to the duration of postoperative administration, each group was further divided into two subgroups, namely, 21 d subgroup (consecutive administration for 21 d, n = 15) and 28 d subgroup (consecutive administration for 28 d, n = 15). After administration, the pathological alterations in multiple organs were observed and the contents of endotoxin, PLA(2), and TNF-alpha in the blood were determined. RESULTS Compared to model control group, the number of dead rats in treated group decreased though there was no statistical difference between the two groups. The pathological alterations in the liver, kidney, and spleen in treated group showed varying degrees of mitigation. At all time points, the contents of plasma endotoxin declined significantly. On day 28, plasma PLA(2) content in treated group was significantly lower than that in model-control group. CONCLUSION Salvia miltiorrhizae injection is able to obviously reduce the contents of inflammatory mediators in the blood of OJ rats and exert some protective effects on multiple organs of these rats.
Collapse
|
|
33
|
Oliveira GP, Oliveira MBG, Santos RS, Lima LD, Dias CM, Ab' Saber AM, Teodoro WR, Capelozzi VL, Gomes RN, Bozza PT, Pelosi P, Rocco PRM. Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2009; 13:R74. [PMID: 19454012 PMCID: PMC2717436 DOI: 10.1186/cc7888] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/02/2009] [Accepted: 05/19/2009] [Indexed: 01/13/2023]
Abstract
INTRODUCTION The protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi. METHODS Seventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively). RESULTS CLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours. CONCLUSIONS In an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.
Collapse
Affiliation(s)
- Gisele P Oliveira
- Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21949-902, Brazil.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
34
|
Zhang M, Qin HL. Advances in hepatic barrier function and injury. Shijie Huaren Xiaohua Zazhi 2009; 17:1008-1013. [DOI: 10.11569/wcjd.v17.i10.1008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatic barrier is a very important structure to protect hepar, and also considerable to protect liver's function. It can prevent endotoxin and virus from entering hepar to damage hepatocyte. The primary aim of this review is to introduce the research status of hepatic barrier and analyze its function and structure. We also introduce several kinds of factors that can induce the failure of the barrier's structure and function and some countermeasures that can resist this factors.
Collapse
|
|
35
|
Cui W, Wen Y, Dong YL, Liu P. Effect of glutamine on intestinal epithelial barrier permeability in vitro. Shijie Huaren Xiaohua Zazhi 2008; 16:3729-3733. [DOI: 10.11569/wcjd.v16.i33.3729] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the mechanism of glutamine (GLN) underlying maintenance of intestinal barrier permeability.
METHODS: Caco-2 cells were placed on Transwell filters and grown in a culture medium composed of DMEM with indicated concentration of GLN (0, 0.1, 1, 4 mmol/L) for 21 d before treatment. Next, transepithelial electrical resistance (TEER) was measured. The localization and expression of tight junction (TJ) protein occludin were measured under immunofluorescence light microscopy. Cells were lysed into detergent-soluble and -insoluble protein fractions and the expression of active or non active occludin protein were measured using Western blot.
RESULTS: Transepithelial electrical resistance was significantly raised following GLN supplementation compared with 0 mmol/L GLN group (21.4 ± 0.1, 124.5 ± 0.3, 173.6 ± 0.2 vs 11.3 ± 0.3, P < 0.05). Immunofluorescence test showed that occludin protein was localized in cytoplasm, with increasing GLN, positive occludin appeared as continuous belt-like structures encircling the cells at the apical cellular junctions in 0 mmol/L GLN group. GLN deprivation did not affect 65-kDa occludin expression, but 85- kDa occludin expression was down-regulated (1.04 ± 0.03, 1.17 ± 0.04, 1.29 ± 0.03, 1.43 ± 0.06, P < 0.05).
CONCLUSION: Deprivation of glutamine decreases active occludin protein expression and increases the intestinal barrier permeability, which is partially reversible with GLN supplementation.
Collapse
|
|
36
|
Assimakopoulos SF, Scopa CD, Vagianos CE. Pathophysiology of increased intestinal permeability in obstructive jaundice. World J Gastroenterol 2008. [PMID: 18161914 DOI: 10.3748/wjg.13.6458] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients' outcome.
Collapse
Affiliation(s)
- Stelios F Assimakopoulos
- Department of Internal Medicine, School of Medicine, University of Patras, Vironos 18, Patras 26224, Greece.
| | | | | |
Collapse
|
|
37
|
Assimakopoulos SF, Scopa CD, Vagianos CE. Pathophysiology of increased intestinal permeability in obstructive jaundice. World J Gastroenterol 2007; 13:6458-64. [PMID: 18161914 PMCID: PMC4611283 DOI: 10.3748/wjg.v13.i48.6458] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome.
Collapse
|
|
38
|
Shiomi H, Shimizu T, Endo Y, Murata S, Kurumi Y, Uji Y, Tani T. Relations among circulating monocytes, dendritic cells, and bacterial translocation in patients with intestinal obstruction. World J Surg 2007; 31:1806-1812. [PMID: 17610111 DOI: 10.1007/s00268-007-9110-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Little evidence is available regarding the relations among circulating monocytes, dendritic cells (DCs), and bacterial translocation (BT) in patients with intestinal obstruction. METHODS We investigated alterations in DCs in mesenteric lymph nodes (MLNs), circulating immune cells (white blood cell, lymphocyte, and monocyte counts), and BT to MLNs in 21 patients undergoing abdominal surgery because of intestinal obstruction. We also examined whether BT correlated with the development of perioperative systemic inflammatory response syndrome (SIRS) and postoperative septic complications. RESULTS BT subsequent to intestinal obstruction was observed in 7 (33%) patients. Preoperative circulating immune cell counts were significantly lower in BT-positive patients than those in BT-negative patients. The presence of preoperative SIRS was also significantly related to BT-positive status. A preoperative monocyte count <290/mm(3) was the best predictive factor for BT in MLNs during intestinal obstruction: sensitivity 85.7%; specificity 92.3%; positive and negative predictive values 85.7% and 92.9%, respectively. The area under the receiver operating characteristic curve was 0.944. The expression of S-100 protein-positive DCs in MLNs significantly increased in BT-positive patients. CONCLUSIONS A significant inverse correlation was observed between the circulating monocyte count and the ratio of DCs among all cells in MLNs (r(2)= 0.259). Postoperative septic complications were 3.3 times more common in BT-positive patients than in BT-negative patients. A significant increase in the expression of DCs in MLNs was observed in patients with BT subsequent to intestinal obstruction. Our findings suggested that a low monocyte count (<290 /mm(3)) and the presence of preoperative SIRS might be useful factors for predicting BT in patients with intestinal obstruction.
Collapse
Affiliation(s)
- Hisanori Shiomi
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Tomoharu Shimizu
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga, 520-2192, Japan.
| | - Yoshihiro Endo
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Satoshi Murata
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Yoshimasa Kurumi
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Yoshitaka Uji
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga, 520-2192, Japan
| | - Tohru Tani
- Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowacho, Otsu, Shiga, 520-2192, Japan
| |
Collapse
|
|
39
|
Feng D, Xu W, Chen G, Hang C, Gao H, Yin H. Influence of glutamine on intestinal inflammatory response, mucosa structure alterations and apoptosis following traumatic brain injury in rats. J Int Med Res 2007; 35:644-56. [PMID: 17900404 DOI: 10.1177/147323000703500509] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes and apoptosis in the intestine. Glutamine has been shown to reduce bacterial translocation and maintain intestine mucosal integrity, but its effects on the inflammatory response, structural alterations and apoptosis in intestinal mucosa following TBI have not been previously investigated. Using the weight-drop method, a right parietal cortical contusion was induced in rats and, for the next 5 days, they were fed either chow alone or chow mixed with glutamine. Intestinal tissue samples were then removed for analysis. Following TBI, glutamine supplementation was found to: decrease intestinal concentrations of interleukin (IL) -1beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6; downregulate intercellular adhesion molecule-1 (ICAM-1) expression; attenuate TBI-induced damage to the intestine structure; and reduce apoptosis. These results suggest that post-TBI glutamine administration could suppress intestinal inflammation, protect intestinal mucosal structure and reduce mucosal apoptosis.
Collapse
Affiliation(s)
- D Feng
- Department of Neurosurgery, Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu Province, China.
| | | | | | | | | | | |
Collapse
|
|
40
|
Sukhotnik I, Agam M, Shamir R, Shehadeh N, Lurie M, Coran AG, Shiloni E, Mogilner J. Oral glutamine prevents gut mucosal injury and improves mucosal recovery following lipopolysaccharide endotoxemia in a rat. J Surg Res 2007; 143:379-84. [PMID: 17574581 DOI: 10.1016/j.jss.2007.02.002] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2006] [Revised: 01/31/2007] [Accepted: 02/06/2007] [Indexed: 11/21/2022]
Abstract
OBJECTIVE To evaluate the effects of oral glutamine in preventing mucosal damage caused by lipopolysaccharide (LPS) endotoxemia in a rat. METHODS Male Sprague Dawley rats, weighing 250 to 280 g, were divided into three experimental groups: CONTR rats (Group A), LPS rats (Group B) were treated with lipopolysaccharide given I.P. at dose 10 mg/kg every 24 h (two injections), and LPS-GLN rats (Group C) were treated with oral glutamine given in drinking water (2%) 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, and enterocyte apoptosis were determined 24 h after last LPS injection. RESULTS LPS rats demonstrated a significant decrease in bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, and villus height and crypt depth in jejunum and ileum compared with sham animals. LPS rats also had a significantly greater Park injury score in jejunum and ileum, a lower cell proliferation index in jejunum and ileum, and higher apoptotic index in jejunum and ileum compared with control rats. LPS-GLN animals showed a significant increase in bowel weight in jejunum, mucosal weight in jejunum and ileum, mucosal DNA in jejunum and ileum, villus height in jejunum and ileum, and cell proliferation index compared with LPS animals. The Park injury score was significantly lower in LPS-GLN rats compared with LPS animals. CONCLUSIONS Oral glutamine supplementation prevents mucosal injury and improves intestinal recovery after LPS endotoxemia in a rat.
Collapse
Affiliation(s)
- Igor Sukhotnik
- Department of Pediatric Surgery, B'nai Zion Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
| | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Wu J, Hong L, Cai W, Tang Q, Shi C. Glutamine attenuates TPN-associated liver injury in infant rabbits. Eur J Pediatr 2007; 166:601-6. [PMID: 17103191 DOI: 10.1007/s00431-006-0294-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2006] [Revised: 08/14/2006] [Accepted: 08/22/2006] [Indexed: 10/23/2022]
Abstract
The aim of this study was to assess the effects of parenteral alanyl-glutamine dipeptide (Ala-Gln) on TPN-associated liver injury. Forty-three New Zealand rabbits (6-8 days old) were divided into three groups: 12 in the control group (maternal fed); 18 in the TPN group (TPN for 10 days); 13 in the Gln-PN group (TPN+Ala-Gln 400 mg kg(-1) day(-1) for 10 days). At the end of the experiment, liver function and histology were evaluated; MDA content of liver tissues and hepatocyte apoptosis by TUNEL assay were also determined. The serum concentration of direct bilirubin and bile acid in the Gln-PN group was significantly lower than TPN group (P < 0.05), but showed no difference compared with the control group. AST level of the Gln-PN group was lower than the other two groups. The light microscopy (LM) features in the TPN group included cholestasis or diffuse steatosis, while in the Gln-PN group, inflammatory infiltration and mild hydropic degenerative changes were mainly found without obvious cholestasis or proliferation of bile ducts. The electron microscopy appearances corresponded with LM findings. The liver MDA content in the Gln-PN group was clearly lower than the TPN group (P < 0.05), and was lower without statistical significance compared with control group. TUNEL assays showed the ratio of apoptotic hepatocytes in the TPN group was the highest among all the groups (44.59 +/- 6.68 vs. 0.92 +/- 0.85 in the control group, P < 0.01; 44.59 +/- 6.68 vs. 4.14 +/- 2.76 in the Gln-PN group, P < 0.01). There were significantly fewer apoptotic hepatocytes in the Gln-PN group. From this study, we found that glutamine dipeptide supplementation could attenuate TPN-associated liver injury in infant rabbits, and could also decrease liver MDA production and hepatocyte apoptosis during total parenteral nutrition.
Collapse
Affiliation(s)
- Jiang Wu
- Clinical Nutrition Center, Department of Pediatric Surgery, Xin Hua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | | | | | | | | |
Collapse
|
|
42
|
Tang ZF, Ling YB, Lin N, Hao Z, Xu RY. Glutamine and recombinant human growth hormone protect intestinal barrier function following portal hypertension surgery. World J Gastroenterol 2007; 13:2223-8. [PMID: 17465506 PMCID: PMC4146849 DOI: 10.3748/wjg.v13.i15.2223] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the effects of combined treatment of glutamine (Gln) and recombinant human growth hormone(rhGH) on intestinal barrier function following portal hypertension surgery.
METHODS: This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups: control group (n = 20) and supplemental group (adding Gln and rhGH, n = 22). Every patient received isocaloric and isonitrogenous standard total parenteral nutrition (TPN) starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein (CRP) levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively.
RESULTS: On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group (33.7 ± 5.5 vs 31.0± 5.4, P < 0.05, (1.17 ± 0.32 vs 1.05 ± 0.15, P < 0.05, 13.94 ± 1.09 vs 12.33 ± 1.33, P < 0.05, and 368.12± 59.25 vs 318.12 ± 45.65, P < 0.05, respectively), whereas the increase in serum TNF-α concentration was significantly reduced (41.02 ± 27.56 vs 160.09 ± 35.17, P < 0.05). The increase in L/M ratio was significantly lower in the supplemental group than in the control group (0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P < 0.05). Moreover, mucosal integrity in the supplemental group was better than in the control group.
CONCLUSION: Postoperative administration of TPN supplemented with Gln and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.
Collapse
Affiliation(s)
- Zhao-Feng Tang
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong Provice, China
| | | | | | | | | |
Collapse
|
|
43
|
Aydogan A, Kismet K, Kilicoglu B, Erel S, Ozcan AH, Gollu A, Yildiz E, Akkus MA. Effects of various enteral nutrition solutions on bacterial translocation and intestinal morphology during the postoperative period. Adv Ther 2007; 24:41-9. [PMID: 17526460 DOI: 10.1007/bf02849991] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Bacterial translocation is the passage of bacteria or endotoxins from the gastrointestinal tract to extraintestinal sites, such as mesenteric lymph nodes, liver, spleen, and bloodstream. In this study, the investigators examined the effects of various enteral nutrients on bacterial translocation and intestinal morphology during the postoperative period. Sixty rats were randomly divided into 5 groups, each of which included 12 animals; cecal mobilization was performed in all groups. Group I rats were fed rat chow and water; group II was given standard enteral nutrients; group III, high-energy enteral nutrients; group IV, enteral nutrients supplemented with fiber; and group V, immunonutrients. Bacterial translocation was detected in mesenteric lymph nodes, spleen, liver, and blood cultures. Changes in the terminal ileum were scored from 0 to 4 with the morphologic scoring system. Bacterial translocation was predominantly detected in mesenteric lymph nodes. Rats fed immunonutrients (group V) showed a significant reduction in bacterial translocation compared with other groups. Although minor morphologic alterations in the villi were observed in groups IV and V, the histologic scores of these groups were not statistically different from the scores of control group members. In the present study, investigators evaluated the effects of various enteral nutritional solutions on bacterial translocation and intestinal morphology during the postoperative period. Enteral diets supplemented with arginine, nucleotides, and omega-3 fatty acids were found to reduce bacterial translocation. The investigators concluded that this effect might be related to improvement in immune function resulting from the use of immunonutrients.
Collapse
Affiliation(s)
- Akin Aydogan
- 4th General Surgery Department, Ankara Training and Research Hospital, Ankara, Turkey
| | | | | | | | | | | | | | | |
Collapse
|
|
44
|
Abstract
PURPOSE OF REVIEW Recent literature has focused on the role of the gut and increased gut permeability as a driver of systemic inflammation in critical illness. Thus, the therapeutic potential for an agent to prevent gut barrier compromise and attenuate gut-derived inflammatory response is significant. RECENT FINDINGS In laboratory and clinical settings, glutamine can attenuate gut permeability following critical illness and injury. Further, recent literature has revealed other mechanisms by which glutamine may attenuate the systemic inflammatory response driven by the gut. These findings reveal that glutamine may act at multiple levels to attenuate gut injury and potential subsequent gut-derived systemic inflammatory response. These mechanisms focus around glutamine's ability to induce the cellular protective stress response in the gut. This leads to enhanced protection of the gut epithelial barrier and attenuation of generation of inflammatory mediators. SUMMARY These mechanistic findings, combined with a limited amount of clinical data showing benefit on gut permeability in illness and injury, indicate more formal studies need to be carried out looking the role of glutamine in gut protection and as an antiinflammatory in critical illness.
Collapse
Affiliation(s)
- Paul E Wischmeyer
- Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
| |
Collapse
|