Therapeutic value of melatonin in an experimental model of liver injury and regeneration

Melatonin has marked antioxidant properties. The aim of the present study was to evaluate the therapeutic effect of melatonin on acute liver injury induced in rats by carbon tetrachloride (CCl4), allyl alcohol (AA) and their combination. A total of 108 male Wistar rats were divided into 12 experimental groups according to their treatment regimen (n = 5-10 rats in each group). Melatonin (100 mg/kg body weight, BW) was administered 6 hr (a) after a single dose of CCl4 (intragastrically 0. 66 mL/kg BW diluted 1:1 v/v with corn oil); (b) a single dose of AA (intraperitonealy, 0.62 mmol/kg BW 1:50 v/v in 0.9% saline solution); and (c) a combination of the above substances. Rats were sacrificed at 24 and 48 hr post-toxin administration and the therapeutic effect of melatonin was investigated by assessment of histopathological changes and lipid peroxidation alterations determined by measuring tissue malondialdehyde plus 4-hydroxy-nonenal (MDA + 4-HNE), plasma MDA and plasma levels of liver enzymes. The levels of a key antioxidant, glutathione (GSH), were measured in liver tissue homogenates. Hepatic necrosis was significantly reduced in the melatonin-treated rats 48 hr after administration of CCl4, AA and CCl4 + AA. The levels of hepatic enzymes in plasma were found to be significantly reduced at 24 and 48 hr in the CCl4 + AA treated rats after melatonin administration. Additionally, MDA and MDA + 4-HNE concentrations were significantly reduced at 24 and 48 hr time-points in all groups that received melatonin. GSH levels were decreased in liver after the toxic substances administration, whereas melatonin reversed this effect. In conclusion, a single dose of melatonin decreased hepatic injury induced by CCl4, AA and CCl4 + AA. The inhibition of the oxidative stress and therefore lipid peroxidation by melatonin in CCl4 and AA administered animals, may constitute the protective mechanism of melatonin against acute liver injury.