Erdosteine Modulates Hepatotoxic Effect on Rats Treated with Cisplatin

Cisplatin (CP) is a widly used anticancer drug against abroad spectrum of malignance, but at high dose, it can produce undesirable effects such as hepatotoxicity. The aim of this study was to investigate the possible protective effect of erdosteine (Erd) against CP-induced biochemical, histopathological changes and hepatotoxicity associated with oxidative stress and inflammatory changes in male albino rats. Animals were randomly divided into four equal groups of 10 rats each as follows: 1-Control group: rats received distilled water, 2CP treated group: rats injected i.p. with CP 7.5 mg / kg body weight, single dose, 3Erd treated group: rats received Erd by gastric tube 100 mg/kg body weight once daily for one week, 4-CPErd group: rats received Erd by gastric tube 100 mg/ kg body once daily for one week before i.p. administration of CP 7.5 mg / kg body weight, single dose. The results of the present study revealed that the administration of CP induced oxidative stress in liver tissues notified by a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione transferase (GST) and reduced glutathione (GSH) content accompanied by a significant increase of thiobarbituric acid reactive substance (TBARS) levels. Concomitant alteration of liver function was denoted by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities. The administration of CP induced also significantly increases of serum tumor necrosis factor alpha (TNF-α), and Interleukin-1β (IL-1β) levels. Histopathological investigation showed degenerative changes, dilated blood vessels, necrosis and apoptosis. Erd treatment before CP administration has significantly attenuated oxidative stress, improved liver function and decreased TNF-α, and IL-1β levels compared to their respective values in the CP group. The amelioration of biochemical variations was associated with an improvement in hepatic tissues architecture. It is concluded that Erd could alleviate CP-induced biochemical and histopathological alternation that can lead to hepatotoxicity.