Melatonin reduces dimethylnitrosamine-induced liver fibrosis in rats.
Increased deposition of the extracellular matrix components, particularly collagen, is a central phenomenon in liver fibrosis. Stellate cells, the central mediators in the pathogenesis of fibrosis are activated by free radicals, and synthesize collagen. Melatonin is a potent physiological scavenger of hydroxyl radicals. Melatonin has also been shown to be involved in the inhibitory regulation of collagen content in tissues. At present, no effective treatment of liver fibrosis is available for clinical use. We aimed to test the effects of melatonin on dimethylnitrosamine (DMN)-induced liver damage in rats. Wistar albino rats were injected with DMN intraperitoneally. Following a single dose of 40 mg/kg DMN, either saline (DMN) or 100 mg/kg daily melatonin was administered for 14 days. In other rats, physiologic saline or melatonin were injected for 14 days, following a single injection of saline as control. Hepatic fibrotic changes were evaluated biochemically by measuring tissue hydroxyproline levels and histopathogical examination. Malondialdehyde (MDA), an end product of lipid peroxidation, and glutathione (GSH) and superoxide dismutase (SOD) levels were evaluated in blood and tissue homogenates. DMN caused hepatic fibrotic changes, whereas melatonin suppressed these changes in five of 14 rats (P < 0.05). DMN administration resulted in increased hydroxyproline and MDA levels, and decreased GSH and SOD levels, whereas melatonin reversed these effects. When melatonin was administered alone, no significant changes in biochemical parameters were noted. In conclusion, the present study suggests that melatonin functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.
Dpeartment of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. veytahan@yahoo.com
Veysel
V
Tahan
Resat
R
Ozaras
Billur
B
Canbakan
Hafize
H
Uzun
Seval
S
Aydin
Beytullah
B
Yildirim
Huseyin
H
Aytekin
Gulsen
G
Ozbay
Ali
A
Mert
Hakan
H
Senturk
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004128:Dimethylnitrosamine / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D008111:Liver Function Tests; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008550:Melatonin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000032:analysis
D000975:Antioxidants; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D008550:Melatonin; D004128:Dimethylnitrosamine; D006909:Hydroxyproline