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Ghobadi Pour M, Mirazi N, Alaei H, Radahmadi M, Rajaei Z, Monsef Esfahani A. The effects of concurrent treatment of silymarin and lactulose on memory changes in cirrhotic male rats. ACTA ACUST UNITED AC 2020; 10:177-186. [PMID: 32793440 PMCID: PMC7416014 DOI: 10.34172/bi.2020.22] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 11/30/2019] [Accepted: 12/14/2019] [Indexed: 12/17/2022]
Abstract
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Introduction: Chronic liver disease frequently accompanied by hepatic encephalopathy (HE). Changes in the permeability of the blood-brain barrier in HE, make an easier entrance of ammonia among other substances to the brain, which leads to neurotransmitter disturbances. Lactulose (LAC), causes better defecation and makes ammonia outreach of blood. Silymarin (SM) is a known standard drug for liver illnesses. The purpose of this research was to determine the results of LAC and SM combined treatment, on the changes in memory of cirrhotic male rats. Methods: The cirrhotic model established by treatment with thioacetamide (TAA) for 18 weeks. Cirrhotic rats randomized to four groups (n = 7): TAA group (received drinking water), LAC group (2 g/kg/d LAC in drinking water), SM group (50 mg/kg/d SM by food), SM+ LAC group (similar combined doses of both compounds) for 8 weeks. The control group received drinking water. The behavior examined by wire hanging (WH), passive avoidance (PA), and open field (OF) tests.
Results: Our findings showed that treatment with SM+LAC effectively increased PA latency, compared with the control group. The results showed that the administration of LAC and SM+LAC affected the number of lines crossed, the total distance moved and velocity in the OF tests. Conclusion: SM and LAC have anti-inflammatory effects that are memory changing. It may be due to their useful effects. These results indicated that SM+LAC restored memory disturbance and irritated mood in the cirrhotic rats. Comparable neuroprotection was never previously informed. Such outcomes are extremely promising and indicate the further study of SM+LAC.
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Affiliation(s)
- Mozhgan Ghobadi Pour
- Department of Biology, Faculty of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran
| | - Naser Mirazi
- Department of Biology, Faculty of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran
| | - Hojatollah Alaei
- Department of Physiology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Maryam Radahmadi
- Department of Physiology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ziba Rajaei
- Department of Physiology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Salman Khan M, Zaka M, Haider Abbasi B, Rahman L, Shah A. Seed germination and biochemical profile of Silybum marianum exposed to monometallic and bimetallic alloy nanoparticles. IET Nanobiotechnol 2016; 10:359-366. [PMID: 27906135 PMCID: PMC8676010 DOI: 10.1049/iet-nbt.2015.0050] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 02/07/2016] [Accepted: 03/07/2016] [Indexed: 11/20/2022] Open
Abstract
In recent years nanotechnology has become increasingly important in almost every field. The new and improved physical, chemical and biological properties of material at nanoscale have far reaching implications in the fields of science and technology. Nanoparticles' effect on various plant species must be investigated to develop a comprehensive toxicity profile for nanoparticles. The current study strives to evaluate the effects of nine types of metal nanoparticles including monometallic and bimetallic alloy nanoparticles [Ag, Au, Cu, AgCu (1:3), AgCu (3:1), AuCu (1:3), AuCu (3:1), AgAu (1:3), AgAu (3:1)] on seed germination, root and shoot growth and biochemical profile of Silybum marianum plant. Seed germination was greatly affected and increased significantly upon treatment with nanoparticles' suspensions and was recorded highest for Ag nanoparticle suspension. Metal nanoparticles also had a significant effect on the biochemical profile of S. marianum. For the first week, the effect on DPPH, total phenolics content, total flavonoids content, total protein content, peroxidase activity and superoxide dismutase activity was enhanced, but declined as the time progressed. Among the nanoparticles being used, the effect of Ag nanoparticle was mostly enhancing. The results obtained are significant in mapping the effects of different monometallic and bimetallic nanoparticles on medicinal plant species.
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Affiliation(s)
| | - Mehreen Zaka
- Department of Biotechnology, Quaid-i-Azam University Islamabad 45320, Pakistan
| | - Bilal Haider Abbasi
- Department of Biotechnology, Quaid-i-Azam University Islamabad 45320, Pakistan.
| | - Latifur- Rahman
- Department of Chemistry, Quaid-i-Azam University Islamabad 45320, Pakistan
| | - Afzal Shah
- Department of Chemistry, Quaid-i-Azam University Islamabad 45320, Pakistan
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3
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Cíž M, Lojek A. Modulation of neutrophil oxidative burst via histamine receptors. Br J Pharmacol 2014; 170:17-22. [PMID: 23336732 DOI: 10.1111/bph.12107] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Revised: 12/17/2012] [Accepted: 12/20/2012] [Indexed: 11/28/2022] Open
Abstract
Histamine has the ability to influence the activity of immune cells including neutrophils and plays a pivotal role in inflammatory processes, which are a complex network of cellular and humoral events. One of the main functions manifested by activated neutrophils is oxidative burst, which is linked to the production of reactive oxygen species; therefore, the effects of histamine receptor agonists and antagonists on the oxidative burst of neutrophils is reviewed. A role for the well-characterized histamine H1 and H2 receptors in this process is discussed and compared to that of the recently discovered H4 receptor.
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Affiliation(s)
- M Cíž
- Department of Free Radical Pathophysiology, Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
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Masini E, Vannacci A, Failli P, Mastroianni R, Giannini L, Vinci MC, Uliva C, Motterlini R, Mannaioni PF. A carbon monoxide‐releasing molecule (CORM‐3) abrogates polymorphonuclear granulocyte‐induced activation of endothelial cells and mast cells. FASEB J 2008; 22:3380-8. [DOI: 10.1096/fj.08-107110] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Emanuela Masini
- Department of Preclinical and Clinical PharmacologyUniversity of Florence Florence Italy
| | - Alfredo Vannacci
- Department of Preclinical and Clinical PharmacologyUniversity of Florence Florence Italy
| | - Paola Failli
- Department of Preclinical and Clinical PharmacologyUniversity of Florence Florence Italy
| | - Rosanna Mastroianni
- Department of Preclinical and Clinical PharmacologyUniversity of Florence Florence Italy
| | - Lucia Giannini
- Department of Preclinical and Clinical PharmacologyUniversity of Florence Florence Italy
| | - Maria Cristina Vinci
- Department of Preclinical and Clinical PharmacologyUniversity of Florence Florence Italy
| | - Caterina Uliva
- Department of Preclinical and Clinical PharmacologyUniversity of Florence Florence Italy
| | - Roberto Motterlini
- Vascular Biology Unit, Department of Surgical ResearchNorthwick Park Institute for Medical Research Harrow Middlesex UK
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5
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Schiavone A, Righi F, Quarantelli A, Bruni R, Serventi P, Fusari A. Use of Silybum marianum fruit extract in broiler chicken nutrition: influence on performance and meat quality. J Anim Physiol Anim Nutr (Berl) 2007; 91:256-62. [PMID: 17516949 DOI: 10.1111/j.1439-0396.2007.00701.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The present study aimed at evaluating the effects of different doses of silymarin in diet on broiler performances and meat quality. For the trial, 180 male chicks (ROSS 508), were allocated in to three groups (S0, S40 and S80) of 60 animals each receiving a basal diet supplemented with 0 ppm, 40 ppm and 80 ppm of a sylimarin (provided by a dry extract of Silybum marianum fruits) respectively. During the trial feed consumption and live body weight were taken every 20 days. At the age of 40 and 60 days blood samples were taken in order to evaluate protein, aspartate aminotransferase, cholesterol, tryglicerides and uric acid. At the age of 60 days animals were slaughtered, dressing percentages were evaluated and samples of breast and meat were taken to evaluate chemical composition and susceptibility of lipid peroxidation by means of thiobarbituric acid reactive substances. Silymarin at the tested doses did not affect growth performances but slightly affected slaughtering yields negatively, no specific hepatoprotective effect was found. Treatments reduced lipid content of both breast and thigh and increased muscles resistance to oxidative stress.
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Affiliation(s)
- A Schiavone
- Dipartimento di Produzioni Animali, Epidemiologia ed Ecologia, Università di Torino, Grugliasco (TO), Italy.
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Jeong DH, Lee GP, Jeong WI, Do SH, Yang HJ, Yuan DW, Park HY, Kim KJ, Jeong KS. Alterations of mast cells and TGF-β1 on the silymarin treatment for CCl 4-induced hepatic fibrosis. World J Gastroenterol 2005; 11:1141-8. [PMID: 15754394 PMCID: PMC4250703 DOI: 10.3748/wjg.v11.i8.1141] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.0] [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: Silymarin is a potent antioxidant, antiinflammatory and anti-fibrogenic agent in the liver, which is mediated by alteration of hepatic Kupffer cell function, lipid peroxidation, and collagen production. Especially, in hepatic fibrogenesis, mast cells are expressed in chronic inflammatory conditions, and promote fibroblast growth and stimulate production of the extracellular matrix by hepatic stellate cells.
METHODS: We examined the inhibitory mechanism of silymarin on CCl4-induced hepatic cirrhosis in rats. At 4, 8, and 12 wk, liver tissues were examined histopathologically for fibrotic changes produced by silymarin treatment.
RESULTS: In the silymarin with CCl4-treated group, increase of hepatic stellate cells and TGF-β1 production were lower than in the CCl4-treated group at early stages. Additionally, at the late fibrogenic stage, expressions of TGF-β1 were weaker and especially not expressed in hepatocytes located in peripheral areas. Moreover, the number of mast cell in portal areas gradually increased and was dependent on the fibrogenic stage, but those of CCl4+silymarin-treated group decreased significantly.
CONCLUSION: Anti-fibrotic and antiinflammatory effects of silymarin were associated with activation of hepatic stellate cells through the expression of TGF-β1 and stabilization of mast cells. These results suggest that silymarin prevent hepatic fibrosis through suppression of inflammation and hypoxia in the hepatic fibrogenesis.
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Affiliation(s)
- Da-Hee Jeong
- College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea
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Savarino L, Benetti D, Baldini N, Tarabusi C, Greco M, Aloisi R, Frascarelli S, Fantozzi R, Dianzani C, Mian M. A preliminaryin vitro andin vivo study of the effects of new anthraquinones on neutrophils and bone remodeling. J Biomed Mater Res A 2005; 75:324-32. [PMID: 16088894 DOI: 10.1002/jbm.a.30426] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Osteolysis, that is, progressive periprosthetic bone loss, is responsible for approximately 70% of aseptic loosening and implant failure. Usually, it is due to a granulomatous reaction wear-induced, leading to macrophage and osteoclast-mediated bone resorption. At present, there is no established prophylaxis or treatment for this process. For this purpose, as a preliminary investigation, we aimed to study the effects in two directions, inhibition of proinflammatory signals, and bone remodeling activity, of two newly synthesized anthraquinone molecules [N,N'-Diethylamino-2,6-anthraquinone-disulfonamide (GR375) and N,N'-(p-ethoxyphenyl)-2,6-anthraquinone-disulfon amide (GR377)]. Among the pro-inflammatory signals, the ability of the two anthraquinones to interfere with the production of superoxide anion (O(2) (-)), which was assumed as a marker of reactive oxygen species (ROS), was evaluated in an in vitro cell model by testing phagocytes, such as human neutrophils, challenged by the chemotactic agent N-formylmethionyl-leucyl-phenylalanine (FMLP). Both compounds inhibited O(2) (-) production, in a dose-dependent way, without exerting scavenger effects. An in vivo model was applied to investigate their effect on bone remodeling. Fifty-four female Wistar rats were divided into eight groups of six animals each, and a 4-week treatment was applied in two phases. A 25 mg/kg/os dose in the first phase and 12.5-6.25 mg/kg/os doses in the second one were employed. The tibia trabecular bone at the secondary spongiosa level was analyzed, and trabecular bone volume (%TBV), trabecular thickness (TbTh), and apatite lattice parameters were measured. At the highest doses of GR375 and GR377 the %TBV and the TbTh increased by 33.2, 34.6%, and 3.6 and 9.1%, respectively, whereas crystallographic parameters were not significantly different from the untreated group. Our results suggest a simultaneous antiinflammatory and antiosteoclastic activity of both drugs that encourages to perform further research. If it will be confirmed, they could be proposed in a variety of bone diseases, in particular, when acute inflammation is associated to osteolytic processes and, eventually, in the prevention and treatment of periprosthetic osteolysis.
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Affiliation(s)
- L Savarino
- Laboratory for Pathophysiology of Orthopaedic Implants, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
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Hur J, Kang MK, Park JY, Lee SY, Bae YS, Lee SH, Park YM, Kwak JY. Pro-apoptotic effect of high concentrations of histamine on human neutrophils. Int Immunopharmacol 2003; 3:1491-502. [PMID: 12946446 DOI: 10.1016/s1567-5769(03)00162-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Histamine receptors are expressed on neutrophils, and therefore, are likely to modulate neutrophil function. In this study, we investigated whether histamine modulates human neutrophil survival. Neutrophils were found to rapidly undergo spontaneous apoptosis upon culture in vitro and this was accelerated by high concentrations of histamine. Moreover, the percentage of apoptotic neutrophils was also markedly increased by treating with 10 mM histamine in the presence of inflammatory mediators, such as lipopolysaccharide (LPS), granulocyte macrophage-colony stimulating factor (GM-CSF), dibutyryl-cAMP (db-cAMP), or dexamethasone. Histamine-induced neutrophil apoptosis was inhibited by pyrilamine, a histamine receptor 1 antagonist, and by ranitidine, a selective histamine receptor 2 antagonist. In addition, diphenylene iodonium (DPI), an inhibitor of NADPH-oxidase, significantly blocked the apoptotic effect of histamine. Moreover, the induction of apoptosis by histamine was almost completely inhibited by zVAD-fmk, a pan-caspase inhibitor. In addition, immunoblotting showed that histamine induced the proteolytic activation of procaspase-3 in cell lysates treated with histamine. And, the protein kinase C (PKC)-delta inhibitor, rottlerin (5 microM) significantly blocked the apoptotic effect of histamine, though the cleavage of PKC-delta in 20 h cultured neutrophils was increased by histamine. However, an inhibitor of conventional PKC, Go6976 (100 nM) and a p38 mitogen-activated protein kinase inhibitor, SB203580 (10 microM), failed to block histamine-induced neutrophil apoptosis. These results suggest that high concentrations of histamine in local inflammatory and allergic lesions induce neutrophil apoptosis, and that this histamine-induced apoptosis is mediated by caspase activation and PKC-delta signaling.
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Affiliation(s)
- Jun Hur
- Department of Oto-Rhino-Laryngology, Dong-A University College of Medicine, South Korea
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9
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Swindle EJ, Hunt JA, Coleman JW. A comparison of reactive oxygen species generation by rat peritoneal macrophages and mast cells using the highly sensitive real-time chemiluminescent probe pholasin: inhibition of antigen-induced mast cell degranulation by macrophage-derived hydrogen peroxide. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2002; 169:5866-73. [PMID: 12421969 DOI: 10.4049/jimmunol.169.10.5866] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Mast cells and macrophages live in close proximity in vivo and reciprocally regulate one another's function in various ways. Although activated macrophages possess a powerful reactive oxygen species (ROS) generating system, there is conflicting evidence regarding whether mast cells can produce ROS. We used the highly sensitive real-time chemiluminescent probe Pholasin to examine ROS release by peritoneal macrophages and mast cells isolated from OVA-sensitized rats. Macrophages stimulated with PMA (0.8 microM) or ionomycin (1 microM), but not OVA (1 microg/ml), released high-level ROS, levels of which peaked after 3-7 min and declined to baseline levels within 1 h. Superoxide was identified as the major ROS species induced by PMA but not by ionomycin. In contrast, purified mast cells stimulated with PMA released low-level ROS, which was entirely due to the contaminating (2%) macrophages, and did not release any detectable ROS in response to ionomycin or OVA at concentrations that induced degranulation. Stimulation of mixed cell populations with PMA to induce macrophage ROS release led to 50% inhibition of serotonin release from mast cells stimulated 5 min later with OVA. The PMA-induced inhibitory factor was identified as hydrogen peroxide. In conclusion, activated rat peritoneal macrophages but not mast cells produce ROS, and macrophage-derived hydrogen peroxide inhibits mast cell degranulation. The latter could be an important mechanism whereby phagocytic cells regulate mast cell activation and promote resolution of IgE-mediated inflammation.
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Affiliation(s)
- Emily J Swindle
- Department of Pharmacology and Therapeutics, Department of Clinical Engineering, University of Liverpool, Liverpool L69 3GE, United Kingdom
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Abraham SN, Malaviya R. Mast cell modulation of the innate immune response to enterobacterial infection. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2000; 479:91-105. [PMID: 10897412 DOI: 10.1007/0-306-46831-x_8] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- S N Abraham
- Department of Pathology and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
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Talkington J, Nickell SP. Borrelia burgdorferi spirochetes induce mast cell activation and cytokine release. Infect Immun 1999; 67:1107-15. [PMID: 10024550 PMCID: PMC96436 DOI: 10.1128/iai.67.3.1107-1115.1999] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could activate mast cells. We report here that freshly isolated rat peritoneal mast cells or mouse MC/9 mast cells cultured in vitro with live or freeze-thawed B. burgdorferi spirochetes undergo low but detectable degranulation, as measured by [5-3H] hydroxytryptamine release, and they synthesize and secrete the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). In contrast to findings in previous studies, where B. burgdorferi-associated activity was shown to be dependent upon protein lipidation, mast cell TNF-alpha release was not induced by either lipidated or unlipidated recombinant OspA. This activity was additionally shown to be protease sensitive and surface expressed. Finally, comparisons of TNF-alpha-inducing activity in known low-, intermediate-, and high-passage B. burgdorferi B31 isolates demonstrated passage-dependent loss of activity, indicating that the activity is probably plasmid encoded. These findings document the presence in low-passage B. burgdorferi spirochetes of a novel lipidation-independent activity capable of inducing cytokine release from host cells.
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Affiliation(s)
- J Talkington
- Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA
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Affiliation(s)
- S N Abraham
- Department of Pathology, Washington University School of Medicine, and Barnes-Jewish Hospital of St. Louis, Missouri 63110, USA.
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Andersson CM, Hallberg A, Högberg T. Advances in the development of pharmaceutical antioxidants. ADVANCES IN DRUG RESEARCH 1996. [DOI: 10.1016/s0065-2490(96)80004-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Guglielmotti A, Capezzone De Joannon A, Cazzolla N, Marchetti M, Soldo L, Cavallo G, Pinza M. Radical scavenger activity of bendazac, an anticataract non-steroidal anti-inflammatory agent. Pharmacol Res 1995; 32:369-73. [PMID: 8736488 DOI: 10.1016/s1043-6618(05)80042-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Oxidative damage to lens components is associated with cataract formation and reactive oxygen species (ROS) overproduction at inflammation sites is thought to lead to the development of inflammatory disorders. Bendazac is a non-steroidal anti-inflammatory drug able to delay the cataractogenic process. Aim of the present study is to characterize, both chemically and biologically, the activity of this anticataract agent as a radical scavenger. Bendazac has been shown to be a strong reacting substrate in a chemical oxidizing system, which mimics a physiological pathway of hydroxy radical generation. In the Fenton-Cier reaction the drug rapidly forms a mixture of hydroxylated derivatives, among which 5-hydroxybendazac, bendazac's main metabolite, being a hydroxy radical scavenger itself. Moreover, by means of a rapid and sensitive flow cytometric method able to determine reactive oxygen intermediate production, bendazac and its 5-hydroxy derivative were shown to inhibit oxidative burst activation in polymorphonuclear neutrophil leukocytes (PMNLs).
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Affiliation(s)
- A Guglielmotti
- Lab. of Immunopharmacology, Angelini Ricerche, Rome, Italy
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Miadonna A, Pesci A, Tedeschi A, Bertorelli G, Arquati M, Olivieri D. Mast cell and histamine involvement in farmer's lung disease. Chest 1994; 105:1184-9. [PMID: 8162747 DOI: 10.1378/chest.105.4.1184] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
The aim of this study was to evaluate the cellular and biochemical characteristics of the bronchoalveolar lavage (BAL) fluid in patients with farmer's lung disease (FLD). Total cell numbers in BAL fluids from patients with FLD (n = 30) were significantly higher than in normal subjects (n = 7; p < 0.01), and differential cell counts were significantly different. Lymphocytes were the most numerous cell type in BAL fluids from patients with FLD (65.4 +/- 2.5 percent vs 6.8 +/- 0.5 percent), and analysis of lymphocyte subsets revealed increased percentages of CD3+ and CD8+ cells (91.8 +/- 0.9 percent vs 68.8 +/- 3 percent, p < 0.01, and 54.3 +/- 3.1 percent vs 30.1 +/- 3.2 percent, p < 0.01, respectively). A marked increase in mast cell numbers, as revealed by the specific alcian blue/safranin staining, was observed in patients with FLD (4.2 +/- 0.57 percent, n = 12, vs 0.18 +/- 0.04 percent, n = 7, p < 0.001). Histamine levels in BAL supernatants were increased in patients with FLD (mean = SEM, 4.4 +/- 0.8 ng/ml vs 0.9 +/- 0.1 ng/ml; median, 2.4 ng/ml vs 0.9 ng/ml, p < 0.01), and correlated positively with mast cell numbers and percentages (r = +0.63, p < 0.03, and r = +0.69, p < 0.02, respectively); conversely, a negative correlation was found between histamine levels and CD8+ lymphocyte percentages (r = -0.48, p < 0.01). Raised neutrophil percentages (5.1 +/- 0.8 vs 0.5 +/- 0.18, p < 0.05) and albumin concentrations (29.2 +/- 3.9 mg/dl vs 3.4 +/- 1.3 mg/dl, p < 0.01) were also found in patients with FLD. These findings show that increased numbers of mast cells, lymphocytes, and neutrophils can be found in BAL fluids of patients with FLD. The increased histamine levels in the supernatants of BAL fluids indicate that mast cells are activated. These data allow us to postulate a role for mast cell accumulation and histamine release in the inflammatory process of FLD.
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Affiliation(s)
- A Miadonna
- Clinica Medica I, Università 0088 di Milano, IRCCS, Ospedale Policlinico, Italy
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Almer S, Franzén L, Olaison G, Smedh K, Ström M. Increased absorption of polyethylene glycol 600 deposited in the colon in active ulcerative colitis. Gut 1993; 34:509-13. [PMID: 8491399 PMCID: PMC1374312 DOI: 10.1136/gut.34.4.509] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
A defect in the barrier function of the intestinal mucosa has been proposed as important in both the pathogenesis and systemic manifestations of inflammatory bowel disease. After colonoscopy, polymers of polyethylene glycol (PEG) with molecular weights of 414-810 (mean 600), were instilled in the descending colon of patients with ulcerative colitis (n = 17) and in controls without intestinal inflammation (n = 8). The patients with active ulcerative colitis (n = 6) had a significantly increased uptake of PEGs in the molecular weight range 458-810, measured as urinary excretion over the first 6 hours after instillation. The median values for their excretion were 2.85-3.80% of PEGs instilled compared with 0.32-0.94% for patients in remission (n = 11) (p < 0.05-0.01) and 0.17-0.60% for the controls (p < 0.05-0.01). The differences in absorption of PEG 414 did not reach the present level of statistical significance. There was a positive correlation between PEG absorption and the endoscopic and histological grading of inflammatory activity in the sigmoid colon (p < 0.01-0.001). These findings support a correlation between the presence of active inflammation and PEG absorption. There was little evidence to support the presence of a primary defect in the colonic barrier in patients with ulcerative colitis.
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Affiliation(s)
- S Almer
- Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Sweden
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Miller MJ, Zhang XJ, Barkemeyer B, Sadowska-Krowicka H, Eloby-Childress S, Gu X, Clark DA. Potential role of histamine monochloramine in a rabbit model of ileitis. Scand J Gastroenterol 1991; 26:852-8. [PMID: 1663272 DOI: 10.3109/00365529109037022] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Histamine chloramines, derived from the chlorination of histamine by granulocyte-derived oxidants, are potential mediators of intestinal injury and dysfunction in states of atopy or inflammation. We assessed the ability of histamine monochloramine to increase epithelial permeability in rabbit distal small intestine and determined whether the conditions for histamine chloramine formation are favorable in a rabbit model of ileitis. Epithelial permeability, quantified by the blood-to-lumen clearance of 51Cr-labeled ethylenediaminetetraacetic acid, was enhanced by luminal perfusion with either histamine or histamine monochloramine (10 microM), although the latter was twice as effective (p less than 0.05). In a rabbit model of ileitis induced by a luminal solution of acetic acid (200 mM) and casein (10 mg/ml) there was a marked increase in epithelial permeability and in the release into the lumen of histamine, myeloperoxidase, 6-keto-prostaglandin F1 alpha and protein. These results suggest that the conditions are favorable for histamine chloramine formation and that histamine and histamine chloramine may impair the integrity of the epithelial barrier.
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Affiliation(s)
- M J Miller
- Dept. of Pediatrics, Louisiana State University Medical Center, New Orleans 70112
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Masini E, Palmerani B, Gambassi F, Pistelli A, Giannella E, Occupati B, Ciuffi M, Sacchi TB, Mannaioni PF. Histamine release from rat mast cells induced by metabolic activation of polyunsaturated fatty acids into free radicals. Biochem Pharmacol 1990; 39:879-89. [PMID: 1690007 DOI: 10.1016/0006-2952(90)90203-w] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Polyunsaturated fatty acids (PUFA: arachidonic and linoleic acid) release histamine from isolated purified rat serosal mast cells only in the presence of oxidizing systems such as phenobarbital-induced rat liver microsomes, prostaglandin-H-synthetase (PHS) or soybean lipoxygenase. The release of mast cell histamine by activated PUFA has a long time-course and the electron microscopical features are consistent with an exocytotic secretion in the case of arachidonic acid and cell lysis in the case of linoleic acid. The phenomenon is associated with a significant increase in malonyldialdehyde (MDA) and conjugated diene generation, suggesting a relationship between histamine release and membrane lipid peroxidation. The secretion of histamine was inhibited by anti-free radical interventions such as D-mannitol, reduced glutathione and alpha-tocopherol. Some cyclooxygenase and lipoxygenase inhibitors, cimetidine and carnitine derivatives, are differentially active in the inhibition of mast cell histamine release by activated arachidonic acid. These results suggest that free radical derivatives of PUFA, generated by metabolic activation, trigger mast cell histamine release.
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Affiliation(s)
- E Masini
- Department of Preclinical and Clinical Pharmacology, Florence University, School of Medicine, Italy
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19
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Casale TB, Little MM, Furst D, Wood D, Hunninghake GW. Elevated BAL fluid histamine levels and parenchymal pulmonary disease in rheumatoid arthritis. Chest 1989; 96:1016-21. [PMID: 2805829 DOI: 10.1378/chest.96.5.1016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
To determine the amount of histamine in BAL fluid in subjects with RA and to ascertain if elevated histamine levels were associated with parameters of active pulmonary disease, we measured BAL fluid histamine levels in 31 subjects with RA and 36 normal subjects. The subjects with RA had a significantly greater mean BAL histamine level than the normal subjects, (313 +/- 154 pg/ml vs 18 +/- 8 pg/ml; p less than 0.05). When the subjects with RA were divided into three groups based on chest radiograms (1 = normal; 2 = pleural disease only; 3 = interstitial or nodular disease), we found that subjects in group 3 had significantly lower values for TLC and D. Subjects in group 3 also had higher percentages of BAL neutrophils and eosinophils and higher BAL histamine levels (group 1, 115 +/- 52 pg/ml; group 2, 30 +/- 30 pg/ml; and group 3, 1,182 +/- 709 pg of histamine per milliliter). Moreover, BAL histamine levels were negatively correlated with TLC (r = -0.46; p = 0.01) and FVC (r = -0.45; p = 0.01) and positively correlated with BAL neutrophils (r = 0.6; p = 0.0003) and BAL eosinophils (r = 0.89; p = 0.0001). These data suggest that the BAL histamine level may be a useful marker to determine the activity of pulmonary disease in RA.
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Affiliation(s)
- T B Casale
- Department of Internal Medicine, Veterans Administration Medical Center, Iowa City
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20
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Casale TB, Trapp S, Zehr B, Hunninghake GW. Bronchoalveolar lavage fluid histamine levels in interstitial lung diseases. THE AMERICAN REVIEW OF RESPIRATORY DISEASE 1988; 138:1604-8. [PMID: 3202511 DOI: 10.1164/ajrccm/138.6.1604] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
We measured bronchoalveolar lavage (BAL) fluid histamine in 36 normal subjects, 32 patients with sarcoidosis, and 28 patients with idiopathic pulmonary fibrosis (IPF). Patients with sarcoidosis and IPF had significantly greater BAL histamine (59 +/- 21 and 203 +/- 42 pg/ml, respectively) than did normal subjects (18 +/- 8 pg/ml). Sarcoidosis patients with Stage 3 chest radiographs had significantly greater BAL histamine than did sarcoidosis patients with radiographic Stages 0, 1, or 2. Sarcoidosis patients with higher BAL lymphocytes also had higher levels of BAL histamine. Furthermore, among the sarcoidosis patients, we found a marked interactive effect between higher BAL lymphocytes and Stage 3 radiographs on BAL histamine. In IPF, subjects with increased BAL lymphocytes had significantly less BAL histamine than subjects with normal levels of lymphocytes. These studies suggest that BAL histamine may be a useful marker (of more active disease and/or poorer prognosis) to be evaluated in prospective studies in patients with sarcoidosis and IPF.
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Affiliation(s)
- T B Casale
- Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa
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21
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Mannaioni PF, Giannella E, Palmerani B, Pistelli A, Gambassi F, Bani-Sacchi T, Bianchi S, Masini E. Free radicals as endogenous histamine releasers. AGENTS AND ACTIONS 1988; 23:129-42. [PMID: 2455972 DOI: 10.1007/bf02142522] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- P F Mannaioni
- Department of Preclinical and Clinical Pharmacology, University of Florence, Italy
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22
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Mian M, Brunelleschi S, Tarli S, Rubino A, Benetti D, Fantozzi R, Zilletti L. Rhein: an anthraquinone that modulates superoxide anion production from human neutrophils. J Pharm Pharmacol 1987; 39:845-7. [PMID: 2891826 DOI: 10.1111/j.2042-7158.1987.tb05131.x] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), the active metabolite of diacetylrhein, which has been reported as an effective antirheumatic drug in man, inhibited superoxide anion production from human neutrophils challenged with N-formylmethionyl-leucyl-phenylalanine (FMLP: IC50, 2 x 10(-5) M) and A23186 (IC50, 10(-5) M), but not with phorbol myristate acetate. In the same concentration range (10(-6)-10(-3) M), the drug did not affect oxy-radical production by a cell-free hypoxanthine-xanthine oxidase system and exerted weak inhibitory effects on FMLP-evoked lysosomal enzyme release. Rhein inhibitory effects on neutrophil functioning may contribute to the overall therapeutic activity of the parent drug, diacetylrhein.
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Affiliation(s)
- M Mian
- Department of Preclinical and Clinical Pharmacology, University of Florence, Italy
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