Uroprotective effects of curcumin in cyclophosphamide-induced haemorrhagic cystitis paradigm.
The possible uroprotective effects of curcumin have been addressed in the current study. Haemorrhagic cystitis was induced by challenging male Swiss albino rats with a single dose of cyclophosphamide (150 mg/kg, i.p.). Curcumin (200 mg/kg, i.p.) was administered for 10 consecutive days followed by a single dose of cyclophosphamide. Haemorrhagic cystitis was well characterized morphologically and biochemically. The hallmark of this toxicity was marked congestion, oedema and extravasation in rat urinary bladder, as well as a marked desquamative damage to the urothelium and severe inflammation in the lamina propria. Leucocytic infiltration was also observed and determined by histopathological examination. Serum level of tumour necrosis factor-alpha was notably elevated associated with apparent hypokalaemia and hyponatraemia. Bladder contents of adenosine triphosphate, reduced glutathione and glutathione-S-transferase activity were markedly reduced. Malondialdehyde level, myeloperoxidase activity and urinary nitrite-nitrate levels, expressed as nitric oxide, were dramatically increased. Prior administration of curcumin ahead of cyclophosphamide challenge improved all the biochemical and histologic alterations induced by the cytotoxic drug. Based on these broad findings, it could be concluded that curcumin has proven uroprotective efficacy in this cyclophosphamide haemorrhagic cystitis model, possibly through modulating the release of inflammatory endocoids, namely tumour necrosis factor-alpha and nitric oxide, improving the energy status and restoring the oxidant/antioxidant balance.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt. hmmarafa@yahoo.com
Hossam M M
HM
Arafa
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D006470:Hemorrhage / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000652:urine; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D003520:Cyclophosphamide; D012964:Sodium; D003474:Curcumin; D011188:Potassium