title: Melatonin protects against endosulfan-induced oxidative tissue damage in rats.
abstract: Endosulfan is a chlorinated cyclodiene insecticide which induces oxidative stress. In this study, we investigated the possible protective effect of melatonin, an antioxidant agent, against endosulfan (Endo)-induced toxicity in rats. Wistar albino rats (n = 8) were administered endosulfan (22 mg/kg/day orally) followed by either saline (Endo group) or melatonin (10 mg/kg/day, Endo + Mel group) for 5 days. In other rats, saline (control group) or melatonin (10 mg/kg/day, Mel group) was injected for 5 days, following corn oil administration (vehicle of endosulfan). Measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were performed in liver and kidney. Furthermore, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine levels, lactate dehydrogenase (LDH) activity were measured in the serum samples, while tumor necrosis factor-alpha (TNF-alpha), interleukin-beta (IL-beta) and total antioxidant capacity (AOC) were assayed in plasma samples. Endosulfan administration caused a significant decrease in tissue GSH and plasma AOC, which was accompanied with significant rises in tissue MDA and collagen levels and MPO activity. Moreover, the proinflammatory mediators (TNF-alpha and IL-beta), LDH activity, AST, ALT, creatinine and BUN levels were significantly elevated in the endosulfan-treated rats. On the other hand, melatonin treatment reversed all these biochemical alterations induced by endosulfan. Our results suggest that oxidative mechanisms play an important role in endosulfan-induced tissue damage and melatonin, by inhibiting neutrophil infiltration, balancing oxidant-antioxidant status and regulating the generation of inflammatory mediators, ameliorates oxidative organ injury as a result of endosulfan toxicity.
authors.affiliation: Department of Pharmaceutical Toxicology, School of Medicine, Marmara University, School of Pharmacy, Istanbul, Turkey.
authors.forename: Gülden Z
authors.initials: GZ
authors.lastname: Omurtag
authors.forename: Ayfer
authors.initials: A
authors.lastname: Tozan
authors.forename: Ahmet Ozer
authors.initials: AO
authors.lastname: Sehirli
authors.forename: Göksel
authors.initials: G
authors.lastname: Sener
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D004726:Endosulfan / Q000633:toxicity*; D005978:Glutathione / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood*; D007306:Insecticides / Q000633:toxicity*; D053583:Interleukin-1beta / Q000097:blood; D007668:Kidney / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018836:Inflammation Mediators; D007306:Insecticides; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D003094:Collagen; D010088:Oxidoreductases; D005978:Glutathione; D004726:Endosulfan