Increased glutathione levels and activity of PON1 (phenyl acetate esterase) in the liver of rats after a single dose of cyclophosphamide: a defense mechanism?

The clinical utility of cyclophosphamide (CYP) as an anticancer drug is limited by its urotoxicity and nephrotoxicity and to a lesser extent by its hepatotoxicity. The present study was undertaken in order to find out the reason why liver is least susceptible of the three organs to CYP-induced damage although it is the major site for drug activation and metabolism. Adult female Wistar rats weighing 200-250 g were administered single intraperitoneal injection of CYP at the dose of 150 mg/kg body weight and sacrificed at various time intervals 6, 16 or 24h after the dose of CYP.

Enhanced PON1 activity in the kidneys of cyclophosphamide treated rats may play a protective role as an antioxidant against cyclophosphamide induced oxidative stress.

Recent studies have shown that paraoxanase (PON1) has protective effect against oxidative stress and hence can act as an antioxidant. A time course study was carried out in order to find out alterations in PON1 activity in cyclophosphamide (CYP) induced renal injury. Eight to ten weeks old female rats were administered CYP at the dose of 150 mg/kg body wt.

Effect of cyclophosphamide treatment on selected lysosomal enzymes in the kidney of rats.

The anti-cancer drug cyclophosphamide (CYP) is nephrotoxic besides being urotoxic thereby limiting its clinical utility. Since the nephrotoxicity of CYP is less common compared to its urotoxicity, not much importance has been given for the study of mechanism of CYP-induced nephrotoxicity. The aim of the present study is to investigate the possible role of lysosomal enzymes in CYP-induced renal damage.