Effect of Storing Temperature on Hepatotoxicity and Nephrotoxicity of Ifosfamide in Female Rat

Abstract

Problem statement: Ifosfamide (IFO) is a cytotoxic alkylating drug used for the treatment of a variety of cancers, although it has been found to induce certain hematological, hepatotoxic and nephrotoxic side effects. This drug is widely used in developing country, especially Iraq, but without caring too much to the storing temperature due to low drug maintaining facilities. The present work was achieved to investigate the effect of different temperature degrees on the toxicity of IFO on liver and kidney of female rats. Approach: Ifosfamide (60 mg Kg^-1 b.wt) stored at different temperature degrees (4, 10 and 25°C) was given to female rats to detect the effect of temperature degrees on hepatotoxicity and nephrotoxicity of this chemotherapeutic drug. A modified technique was used for demonstration the dying kidney cells. Results: All IFO treated rats showed Fanconi syndrome such as increase of serum creatinine, phosphorus, ALT and AST and decrease of glucose as well as an increase in serum Malondialdehyde (MDA) level. Ifosfamide was still maintained its antimitotic action in all the treated groups as revealed by examining the bone marrow smears. The biochemical estimation of ALT, AST and MDA showed significant temperature dependent increase in the toxicity of liver and kidney by this drug. The histopathological alteration in these two organs were come supportive to the above biochemical results. The liver of the rats exposed to IFO stored at 25°C showed higher liver steatosis, hemorrhage and more degeneration of hepatocytes. Similarly, more hemorrhage, degeneration of kidney tubule cells and lymphocytes infiltration in kidney were observed in the 25°C group in comparison to the other groups. A successful modified technique for staining thick plastic sections was employed revealing a specific color for the dying kidney cells. Conclusion: Although it can maintain its antimitotic property, IFO caused more severe hepatotoxic and nephrotoxic side effects if it is stored at temperature degree higher than 4°C.