An investigation on possible liver damage and protective effect of melatonin in toluene-inhaled Rats

This study was designed to investigate the harmful effects of toluene inhalation and protective effects of melatonin in the liver of ratsFor this purpose, 21 adult male Wistar-albino rats (200-220 g) were randomly divided into three equal groups. Animals in group I were used as control group. The rats in group II were exposed toluene (3000 ppm/1hour/day) for 4 weeks, while the rats in group III treated with melatonin (10 mg/kg/day, ip) plus toluene inhalation.At the end of the experimental period, the liver and blood samples were taken from the decapitated animals. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and albumin levels were determined. Liver tissue sections were stained with routine histological methods and examined under the light microscope. In addition, the samples were immunohistochemically stained using avidin-biotin-peroxidase method for determination of apoptosis. The liver tissue activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) levels were measured.Toluene significantly increased serum ALT, AST and tissue MDA, and decreased serum albumin, but did not affect serum ALP, total bilirubin and tissue SOD, GSH-Px and CAT levels when compared with controls. The increases in tissue MDA, and serum ALT and AST levels induced by toluene inhalation were significantly inhibited by melatonin treatment, while no significant change was observed in serum albumin level.In light microscopic examination of liver tissues from rats inhaled toluene, fatty change, ballooning degeneration, dilated and hyperemic sinusoids, and mild pericentral fibrosis were observed. In addition, immunohistochemical examination showed that Bax immunoreactivity was significantly increased compared with controls. Melatonin treatment significantly decreased Bax immunoreactivity and considerably ameliorates the histopathological changes.In conclusion, this biochemical, histopathological and immunohistochemical study revealed that toluene inhalation causes oxidative injury and apoptosis in the liver, and that melatonin treatment significantly prevents these events.