Abstract
Cefepime belongs to the fourth generation cephalosporin family of antibiotics, it showed side effects such as nephrotoxicity and neurotoxicity. However little reports showed its hepatotoxic effects. The aim of the current study was to evaluate cefepime-induced hepatotoxicity and its associated histopathological changes in the liver. Also, it aimed to examine the effects of cefepime treatment on the proinflammatory cytokines as well as the protective and recovering roles of vitamin C against the cefepime-induced effects. Blood samples were collected and the liver enzymes in serum ALT, AST and Total Bilirubin (T. Bil.) were estimated biochemically; liver tissues were collected and divided into two parts: the first part were fixed for histopathological examination by H&E staining whereas the other part was processed for RNA extraction and further for real time PCR examination of the mRNA expression of IL1 beta and TNF alpha. Cefepime could significantly increase the concentration of ALT, AST, T. Bil. as well as the mRNA expression of proinflammatory cytokines IL1 beta and TNF alpha; histopathological changes in the form of hepatic lobules distortion, marked degeneration, hepatocellular vacuolation and necrosis, nuclear pyknosis, scattered apoptosis, distortion of portal areas and marked fibrosis were observed after two weeks of cefepime administration; coadministration of vitamin C with cefepime or administration administering it for 7 days after cefepime could successfully improve the levels of ALT, AST, T. Bil., histopathological and mRNA expression of IL1 beta and TNF alpha. The current study suggested that cefepime has hepatotoxic effects shown as alternation of the liver enzymes, changing in the histopathological features as well as stimulating the inflammation in the liver tissue. Vitamin C can be used as a protective or recovering drug against cefepime-induced hepatotoxicity.