Hepatotoxicity and its Mechanism(s) Induced by Ifosfamide on Rats

Objective In order to investigate the hepatotoxicity and its mechanism(s) induced by Ifosfamide(Ifo).Mehods Serum biochemical parameters and the contents of malondialdehyde(MDA),sulfhydryl groups and Cyt-P450 in male Wistar rats liver tissue were detected on days 1,4,7,10 after administration of Ifo(40mg·kg^-1·d^-1×5d ip,200mg·kg^-1·d^-1 ×1d ip).Results Serum biochemical parameters and ocncentration of MDA in liver tissue didn't change significantly in both treated groups while total、noneprotein、protein bound sulfhydryl and total P450 contents in liver tissue declined time dependently respectively with be lowest contents on day 7 and a little recovery on day 10.The decrease of protein bound sulfhydryl was ascribed to total sulfhydryl's depletion.However,the chages caused by repeated administraiton is more significant than single administration.In the pathologic examination,the hepatocytes in the central zone of the hepatic lobule were found vacuolation,spotty and focal necroses of hepatocytes in the liver were also found with chronic inflammatory cells infiltration in the necrotic and portal areas.The pathologic changes under the ultrastructure level were mitochondrial swelling、endoplasmic reticulum dilation and secondary lysosomes collection.Conclusion The results indicated that Ifo could induce hepatotoxicity on rats.The changes of sulfhydryl states and inhibition of Cyt-P450 were contributed to the liver injury induced by Ifo.