Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats.
The urotoxicity of cyclophosphamide and the protective effect of the herb berberine were investigated in this study. Administration of 150 mg/kg cyclophosphamide intraperitoneally caused a serious haemorrhagic cystitis in rats after 12 hr, including bladder oedema, haemorrhage, and dramatic elevation of nitric oxide metabolites (nitrite+nitrate) in urine and in plasma. To explore whether cyclophosphamide-induced cystitis could be prevented by berberine, rats were pretreated with a single dose or two doses of berberine at 50, 100, or 200 mg/kg intraperitoneally then challenged with cyclophosphamide (150 mg/kg, intraperitoneally). The results indicated that pretreatment of rats with berberine could reduce cyclophosphamide-induced cystitis in a dose-dependent manner. Furthermore, we found that two doses of berberine showed greater protection against cyclophosphamide urotoxicity than when given a single dose. In addition, our data shows that a single dose of 200 mg/kg berberine, or two doses of 100, and 200 mg/kg berberine could completely block cyclophosphamide-induced bladder oedema and haemorrhage, as well as nitric oxide metabolites increase in rat urine and plasma. In conclusion, our findings suggest that berberine could be a potential effective drug in the treatment of cyclophosphamide-induced cystitis, and provides us with the bright hope in the prevention and treatment of cyclophosphamide urotoxicity.
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Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, Florida 33328, USA.
Malavé
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D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D003556:Cystitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D009573:Nitrites / Q000652:urine; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology
D009566:Nitrates; D009573:Nitrites; D001599:Berberine; D009569:Nitric Oxide; D003520:Cyclophosphamide