title: Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats.
abstract: Nonalcoholic steatohepatitis (NASH) may progress to advanced fibrosis and cirrhosis. Mainly, oxidative stress and excessive hepatocyte apoptosis are implicated in the pathogenesis of progressive NASH. Melatonin is not only a powerful antioxidant but also an anti-inflammatory and anti-apoptotic agent. We aimed to evaluate the effects of melatonin on methionine- and choline-deficient diet (MCDD)-induced NASH in rats. Thirty-two male Wistar rats were divided into four groups. Two groups were fed with MCDD while the other two groups were fed a control diet, pair-fed. One of the MCDD groups and one of the control diet groups were administered melatonin 50 mg/kg/day intraperitoneally, and the controls were given a vehicle. After 1 month the liver tissue oxidative stress markers, proinflammatory cytokines and hepatocyte apoptosis were studied by commercially available kits. For grading and staging histological lesions, Brunt et al.'s system was used. Melatonin decreased oxidative stress, proinflammatory cytokines and hepatocyte apoptosis. The drug ameliorated the grade of NASH. The present study suggests that melatonin functions as a potent antioxidant, anti-inflammatory and antiapoptotic agent in NASH and may be a therapeutic option.
authors: Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey. vet2@pitt.edu
authors: Veysel
authors: V
authors: Tahan
authors: Ozlen
authors: O
authors: Atug
authors: Hakan
authors: H
authors: Akin
authors: Fatih
authors: F
authors: Eren
authors: Gulgun
authors: G
authors: Tahan
authors: Ozlem
authors: O
authors: Tarcin
authors: Hafize
authors: H
authors: Uzun
authors: Osman
authors: O
authors: Ozdogan
authors: Orhan
authors: O
authors: Tarcin
authors: Nese
authors: N
authors: Imeryuz
authors: Fehmi
authors: F
authors: Ozguner
authors: Cigdem
authors: C
authors: Celikel
authors: Erol
authors: E
authors: Avsar
authors: Nurdan
authors: N
authors: Tozun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002794:Choline / Q000378:metabolism; D002796:Choline Deficiency / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D004032:Diet; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006651:Histocytochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D008715:Methionine / Q000172:deficiency* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D008315:Malondialdehyde; D008715:Methionine; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin; D002794:Choline