Effect of cyclophosphamide on liver in albino rats: a comparative dose dependent histomorphological study.

Abstract

Cyclophosphamide is a commonly used anti cancer drug used in almost all regimens for treating a wide variety of carcinomas. It is a prodrug that gets activated in the liver subjecting the organ to a very high amount of the drug influx affecting its functions. The resulting hepatotoxic side effects of cyclophosphamide are dose-dependent as confirmed by studies based on enzymes levels. Recently, low dose cyclophosphamide regimen administered for prolonged periods is documented to be effective in controlling tumor growth and demonstrate a low overall toxicity profile with prolongation of survival. Therefore, the present study was conducted to compare and correlate histomorphological alterations in liver of adult Wistar albino rat induced by a bolus high dose and a divided low dose drug regime of cyclophosphamide administered intraperitoneally. The histomorphological analysis of liver from high dose experimental group demonstrated hepatocellular destruction associated with sinusoidal enlargement and inflammatory infiltration which was more extensive and widespread throughout the parenchyma. Whereas, these changes were observed to be absent or minimal in the low dose experimental group. In fact, the latter showed many binucleate cells and a number of basophilic nuclei containing mitotic figures marking a regenerative response. Hence, cyclophosphamide induces greater hepatodestructive changes at high doses but at low doses, it elicits a regenerative response. Since, prolonged anti cancer treatment with low dose cyclophoshamide has been proven to be efficacious, it is suggested that its dose regimen can be modified accordingly to provide maximum efficacy to the patients but with reduced concomitant toxicity.