title: Uroprotective effect of pentoxifylline in cyclophosphamide-induced hemorrhagic cystitis in rats.
abstract: 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.
authors.affiliation: Department of Laboratory Sciences and Clinical Technology, College of Applied Medical Sciences, Taif University, Taif, Kingdom of Saudi Arabia. oabosalem@yahoo.com
authors.forename: Osama M
authors.initials: OM
authors.lastname: Abo-Salem
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000494:pharmacology; D003556:Cystitis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010431:Pentoxifylline / Q000493:pharmacokinetics*; D051381:Rats; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D016207:Cytokines; D016166:Free Radical Scavengers; D009569:Nitric Oxide; D008315:Malondialdehyde; D003520:Cyclophosphamide; D010088:Oxidoreductases; D010431:Pentoxifylline
keywords: Cyclophosphamide; Hemorrhagic Cystitis; Pentoxifylline; Uroprotective