Study on toxicity mechanism(s) of ifosfamide in suspending cultured rat hepatocytes / 军事医学科学院院刊

ABSTRACT

Objective：To study the toxicity mechanism(s) of ifosfamide(Ifo) in suspending cultured rat hepatocytes.Methods：Hepatocytes of adult rat were isolated using two-step perfusion method and cultured suspendingly. Cell viability,intracellular enzyme leakage, contents of sulfhydryl groups and MDA contents of hepatocytes were examined 3 hours after ifosfamide was administered at 5,10,20 mmol/L. Surface and ultrastructure of hepatocytes were also observed. Results：Cell viability and TSH,NPSH,PSH contents of hepatocytes significantly declined, and LDH,AST activities in media increased due to the leakage of intracellular enzymes. The decrease in PSH content was ascribed to depletion of TSH. The higher the dose was, the more serious these changes became. However, MDA contents of the hepatocytes were not found increased at any ifo dose groups. In pathological examination, “bulla" formation was found on the surface of the hepatocytes, deformation，swelling even vacuolation of mitochondria and dilation of rough，smooth endoplasmic reticulum were also observed. Conclusions：Ifo has toxic effect on suspending cultured rat hepatocytes. The decrease in sulfhydryl groups contributes to the hepatotoxicity induced by Ifo.