Ameliorative effect of vitamin C against 5-fuorouracil-induced hepatotoxicity in mice: A light and electron microscope study

Abstract

5-Fluorouracil is one of the most widely used chemotherapeutic agents in case of hepatic neoplasms. The object of this study was to determine the effectiveness of vitamin C in alleviating 5-fluorouracil-induced hepatotoxicity in male mice. Thirty male albino mice were divided equally into 3 groups, each of 10 animals; group 1, mice received normal saline solution (control group); group 2, mice received 5-fluorouracil 80mg/kgb.wt./day intraperitoneally for 4weeks (5-fluorouracil group); group 3, mice received 5-fluorouracil 80mg/kgb.wt./day for 4weeks with daily injection of vitamin C (12mg/kgb.wt./day) for 4weeks. Animals of all groups were sacrificed and tissue samples from the liver were taken and processed for both light and electron microscopical examination. Light microscopic observations revealed that administration of 5-fluorouracil causes variable signs of hepatotoxicity which are represented by focal areas of liver cell necrosis with distortion of normal hepatic architecture; the hepatocytes showed vacuolated cytoplasm and pyknotic nuclei together with inflammatory cell infiltration. Dilated, congested hepatic sinusoids with active kupffer cells were also seen. Ultrastructure examination confirmed the light microscopic findings and demonstrated vacuolated hepatocytes cytoplasm, dilated endoplasmic reticulum, increased lysosomes, electron-dense mitochondria and pyknotic nuclei. Treatment with vitamin C with 5-fluorouracil attenuated 5-fluorouracil-induced hepatotoxicity and reverted the abnormal structural changes to near normal. In conclusion, these results suggest that vitamin C has a protective potential in ameliorating 5-fluorouracil-induced hepatotoxicity.