Uroprotective Effect of Pentoxifylline in Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats


  • Osama M. Abo-Salem

    Corresponding authorCurrent affiliation:
    1. Department of Pharmacology and Toxicology, Faculty of Pharmacy (Boy), Al-Azhar University, Nasr City, Cairo, Egypt
    • Department of Laboratory Sciences and Clinical Technology, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia
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  • Contract grant sponsor: Deanship Graduate and Scientific Research, Taif University, Taif, Kingdom of Saudi Arabia.

  • Contract grant number: 2023-433-1.

Correspondence to: Osama M. Abo-Salem.


The role of phosphodiesterase inhibitor, pentoxifylline, in the prevention of cyclophosphamide-induced hemorrhagic cystitis was evaluated in a rat model. Hemorrhagic cystitis was induced in rats by an intraperitoneal (i.p.) injection of a single dose of cyclophosphamide (150 mg/kg). Pentoxifylline (150 mg/kg/day/ip) was administered for 10 days followed by cyclophosphamide. Hemorrhagic cystitis was well characterized macroscopically, microscopically, and biochemically. Cyclophosphamide induced bladder injury including acute severe inflammation, vascular congestion, severe edema, hemorrhage, inflammatory cell infiltration in the lamina propria, and epithelial denudation; as well as it notably elevated serum inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β), bladder content of malondialdehyde and total nitrate, accompanied with depletion of bladder antioxidant enzymes activities (glutathione peroxidase, superoxide dismutase, glutathione-S-transferase, and catalase). Prior administration of pentoxifylline improved all biochemical and histologic alterations induced by the cytotoxic drug cyclophosphamide. In conclusion, pentoxifylline has proven uroprotective efficacy in the cyclophosphamide-induced hemorrhagic cystitis model, possibly through modulating the release of inflammatory cytokines and nitric oxide and restoring the oxidant/antioxidant balance. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:343-350, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21494