A histopathological evaluation on the effect of captopril in cyclophosphamide-induced hemorrhagic cystitis

Abstract

Cyclophosphamide is one of the most prescribed antineoplastic agents. Hemorrhagic cystitis is one of the most common side effects of cyclophosphamide. Captopril is usually used as an anti-blood pressure agent. On the other hand, as a thiol group-containing agent, captopril has potent antioxidant activity. This study aims to evaluate the effect of captopril on cyclophosphamide-induced hemorrhagic cystitis in rats. Twenty-five male Sprague-Dawley rats were equally divided into five groups. Group I received saline (10 ml/kg, i.p.), Group II received a single dose of Cyclophosphamide (200 mg/kg, i.p), Groups III-V received cyclophosphamide and mesna (40 mg/kg, i.p.) or captopril (20 and 40 mg/kg, i.p.). Histopathological changes of bladder, liver, and kidney and lipid peroxidation and glutathione contents in the kidney and liver were monitored. Moreover, serum markers of organ injury were measured. It was found that captopril (20 and 40 mg/kg, i.p) and mesna (40 mg/kg, i.p), as the standard treatment of cyclophosphamide-induced hemorrhagic cystitis, conspicuously attenuated the macroscopic and microscopic damage in the bladder induced by cyclophosphamide. In contrast, mesna did not significantly improve histopathological changes. No significant difference in the serum level of liver and kidney injury biomarkers, tissue biomarkers of oxidative stress, and histopathological alteration were detected between control and cyclophosphamide-treated animals. On the other hand, both captopril and mesna alleviated histopathological bladder changes. Although the mechanism of action of captopril seems not to be mediated by alleviating oxidative stress, the present study results indicate that this drug could have a protective effect on cyclophosphamide-induced hemorrhagic cystitis.