One of the major side effects of
cyclophosphamide (CPX)-an alkylating anticancer
drug that is still clinically used-is urotoxicity with
hemorrhagic cystitis. The present study was designed to evaluate the ability of
carvedilol to protect rats from
cyclophosphamide-induced urotoxicity. Rats were injected intraperitoneally (i.p.) with CPX (200 mg/kg) and administered
carvedilol (2 mg/kg) intragastrically a day before, at the day and a day after a single i.p. injection of CPX, with or without
mesna (40, 80, and 80 mg/kg i.p. 20 min before, 4 h and 8 h after CPX administration, respectively). Pretreatment with
carvedilol partly prevented the CPX-induced increase in urinary bladder and kidney index, and completely protects from CPX-evoked alterations in serum
potassium and
creatinine level, but did not prevent histological alterations in the urinary bladder and
hematuria. However,
carvedilol administration resulted in significant restoration of kidney
glutathione (GSH) level and a decrease in kidney
interleukin 1β (IL-1β) and plasma
asymmetric dimethylarginine (ADMA) concentrations. Not only did
mesna improve kidney function, but it also completely reversed histological abnormalities in bladders and prevented
hematuria. In most cases, no significant interaction of
carvedilol with
mesna was observed, although the effect of both drugs together was better than
mesna given alone regarding plasma ADMA level and kidney IL-1β concentration. In conclusion,
carvedilol did not counteract the injury caused in the urinary bladders but restored kidney function, presumably via its
antioxidant and anti-inflammatory properties.