Histopathological and biochemical assessment of liver damage in albino Wistar rats treated with cytotoxic platinum compounds in combination with 5-fluorouracil

INTRODUCTION: Chemotherapy-induced hepatotoxicity in cancer patients often results in cessation of therapy and prevents completion of the treatment plan. The entire pathological description and comparison of hepatic damage induced by oxaliplatin or cisplatin in combination with 5-fluorouracil (5-FU) is not adequately reported. This study reports histopathological assessment of hepatotoxicity of a non-tumor bearing organ in rats treated with 5-FU, oxaliplatin and cisplatin (CDDP). MATERIAL AND METHODS: Changes in hepatic biochemical profile of 36 albino Wistar rats equally divided into different treatment groups with cisplatin, oxaliplatin, 5-FU, cisplatin plus 5-FU and oxaliplatin plus 5-FU were compared with a group of rats treated with normal saline (control group). At the end of treatments, hepatic tissues were taken for blinded histopathological assessment by light microscopy. RESULTS: Serum glutamate pyruvate transaminase and serum glutamic-oxaloacetic transaminase levels were disrupted in rats treated with 5-FU alone and in combination with cisplatin or oxaliplatin. Hepatocellular injuries, e.g. sinusoidal dilatation, venular fibrosis and centrilobular vein injury induced by oxaliplatin were intensified in treatment groups also receiving 5-FU, manifested as massive architectural distortion, periportal fibrosis, hepatic cord degeneration and cystic lesions with demarcated margins. Hepatocellular degenerative sequence and abnormally dilated central hepatic vein was shown in the cisplatin plus 5-FU treatment group with hemorrhage and blood filled sinusoids. CONCLUSIONS: Oxaliplatin-associated cystic lesions were intensified in rats treated with a combination of 5-FU and oxaliplatin.