15-Deoxy-Δ12,14-prostaglandin J2 attenuates development of cyclophosphamide-induced cystitis in rats

ObjectivesTo investigate whether an endogenous prostaglandin (PG) D2 metabolite, 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), can attenuate cyclophosphamide (CYP)-induced cystitis in the rat.MethodsMale Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg). In a separate group of animals, 15d-PGJ2 (10 and 100 μg/kg intraperitoneal bolus 10 minutes before and 24 hours after CYP injection) or a selective inducible nitric oxide synthase (iNOS) inhibitor, N-(3-(aminomethyl)benzyl)acetamidine ([1400W] 10 mg/kg intraperitoneal bolus 10 minutes before and 12 and 24 hours after CYP injection), was administered. At 48 hours after CYP injection, the rats were killed, and tissues were removed for evaluation of cystitis.ResultsCYP injection resulted in severe cystitis. 15d-PGJ2, as well as 1400W, significantly reduced the increase in plasma protein extravasation (Evans blue dye method), iNOS enzymatic activity, urinary excretion of nitric oxide metabolites, and myeloperoxidase activity in the bladder caused by CYP. Moreover, 15d-PGJ2 significantly decreased the cytokine interleukin-1β in the bladder. In addition, 15d-PGJ2 significantly reduced the degree of CYP-induced bladder tissue damage and increase in immunohistochemical staining for iNOS in the bladder.ConclusionsThese results indicate that 15d-PGJ2 can attenuate the development of CYP-induced cystitis by suppression of cytokine production and iNOS induction. Thus, treatment with cyclopentenone prostaglandins such as 15d-PGJ2 may be effective against CYP-induced cystitis.