Vitamin C Ameliorates the Cefepime-Induced Changes of Liver Enzymes, Histopathology and Proinflammatory Cytokines in Male Albino Rats

Life Sciences-Pharmacology For Better Treatment

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 IL1β and TNFα. Cefepime could significantly increase the concentration of ALT, AST, T. Bil. as well as the mRNA expression of proinflammatory cytokines IL1β and TNFα; 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;  co- administration 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 IL1β and TNFα. 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.