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.