Abstract
The fact that cisplatin (CIS) can induce hepatotoxicity has limited its therapeutic uses, although it is recognised as a highly potent antineoplastic drug. Bee venom (BV) is an important toxin that exerts a potent anti-inflammatory effect and demonstrates significant pharmacological activities. The aim of this research was to investigate the therapeutic impact of BV administration orally on CIS-induced hepatotoxicity in a rat model when compared with individual drug therapy. Thirty albino male rats were used in this study. The rats were classified into three groups, each with ten rats (n = 10). The control group was group I, while groups II and III got CIS (a single dose of 7.5 mg/kg interperitoneally). After 24 hours, group III received BV (1 mg/kg orally), which was then administered daily for four weeks. The rats' serum liver functions were estimated. The oxidative stress, antioxidant status, inflammatory mediators and fibrogenic and apoptotic markers were determined in the liver tissues. The results revealed that the administration of CIS induced a significant elevation in the serum aspartate aminotransferase, alanine aminotransferase and bilirubin levels, which was associated with a decrease in the albumin level. Additionally, significant increases in the hepatic tissue malondialdehyde, tumor necrosis factor alpha, interferon gamma, transforming growth factor beta, fibronectin and caspase-3 levels were noted. Moreover, significant decreases in the superoxide dismutase and catalase activities as well as the glutathione level were detected in the hepatic tissues. The administration of BV resulted in the notable amelioration of the aforementioned parameters. Interestingly, these parameters were restored to almost normal levels following administration of CIS and BV. The histopathological investigation revealed multiple focal inflammation sites that appeared to be associated with hepatic necrosis in the hepatic tissues of the CIS-treated rats. The co-administration of BV preserved the normal architecture of the hepatic tissues. These results indicate that the co-administration of BV exerts potent anti-hepatotoxic and cytoprotective effects by combating oxidative stress, inflammation, fibrogenic and apoptotic markers and histopathological changes. Thus, this study provides strong evidence of the superiority of combination drug therapy when compared with individual drug therapy.