Protective effects of ursolic acid on cyclophosphamide induced hemorrhagic cystitis in rats

Abstract

Cyclophosphamide (CP) is a commonly used antineoplastic agent despite its adverse effects. Hemorrhagic cystitis (HC)
is one of the most common side effects of CP. Although Mesna is commonly used to prevent HC, it suffers from few side
effects. Therefore, search for better alternate substance still continues. In this study, we studied the effects of ursolic acid
(UA), one of the active ingredients of Plantago major, commonly called plantain or white man’s foot, in CP-induced
hemorrhagic cystitis in rats. Forty-nine Sprague−Dawley rats in seven equal groups viz. control (C); cyclophosphamide
(CP); cyclophosphamide+Mesna (CPMesna); cyclophosphamide+ursolic acid [100 (CPUA100) and 200 mg (CPUA200)],
and cyclophosphamide+ mesna+ ursolic acid (100, (CPMesnaUA100) and (200 mg (CPMesnaUA200) were investigated for
inducible nitric oxide synthetase (iNOs), total antioxidant status (TAS), total antioxidant status (TOS), TNF–α, interleukin
10 (IL–10) and interleukin 6 (IL–6) levels from blood samples. The data obtained were statistically analyzed using SPSS
and both Kruskall Wallis and Dunn tests were performed. Value of P <0.05 was considered as statistically significant. Our
results have revealed that the UA applied groups better preserve compared to CP group. However, it was observed that this
protection is comparatively weaker than the Mesna and UA-Mesna combinations. Hence, it is suggested that the urosilic
acid could prevent cyclophosphamide induced hemorrhagic cystitis, and also extends support to Mesna applications.
Overall, it has been observed that ursolic acid has limited protective effects against CP-induced hemorrhagic cystitis, and
can serve as a supportive agent in inhibiting hemorrhagic cystitis.