title: Melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress.
abstract: Melatonin is reported to exhibit a wide variety of biological effects, including antioxidant and anti-inflammatory. Evidence shows the important role of oxidative stress in the etiopathogenesis of hepatic fibrosis. The aim of this study was to investigate the protective effects of administration of melatonin in rats with carbon tetrachloride-induced fibrosis for 6 weeks. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examinations. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) levels were evaluated in tissue homogenates by spectrophotometry. The nuclear factor-kappaB (NF-kappaB) in liver tissue was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations in Kupffer cells (KCs) culture supernatants were measured with ELISA. The rats injected subcutaneously with CCl4 for 6 weeks resulted in hepatic fibrotic changes increased hydroxyproline and MDA levels, and decreased GSH-px and SOD levels, whereas melatonin reversed these effects. Furthermore, melatonin inhibited the expression of NF-kappaB in liver tissue and decreasing production of proinflammatory cytokines such as TNF-alpha and IL-1beta from KCs in fibrotic rats. These present results suggest that melatonin ameliorates carbon tetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stress and proinflammatory cytokines production.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China. wanghua@ahmu.edu.cn
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Ni-Ping
authors.initials: NP
authors.lastname: Wang
authors.forename: Shuang-Yin
authors.initials: SY
authors.lastname: Gui
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Wu-Yi
authors.initials: WY
authors.lastname: Sun
authors.forename: Shu-Yun
authors.initials: SY
authors.lastname: Xu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D005979:Glutathione Peroxidase / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D012712:Serum Globulins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012709:Serum Albumin; D012712:Serum Globulins; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008550:Melatonin; D006909:Hydroxyproline