Protective effects of quercetin and bradykinin potentiating peptide against busulfan-induced pathological alterations in rats

Busulfan (BUS) is an alkylating anticancer agent for treatment of hematologic malignancies with toxic effects on various body organs. The present study was built up to investigate the ameliorative effect of Quercetin (QCT), bradykinin potentiating peptide (BPP) and their combination against BUS-induced pathological alterations in Sprague Dawley (SD) rats. Treatment of rats with two doses of BUS (10 mg/kg b.w.) with 21 day intervals notably affected the liver, kidney and brain. In the liver, it induced vacuolar degeneration, nuclear enlargement of hepatocytes, Kupffer cell hyperplasia, and fibroblastic proliferation and mononuclear infiltration in portal areas. The most common kidney lesions as the result of BUS treatment were glomerular swelling, tubular degeneration, and fibroblastic proliferation, and mononuclear cell infiltration in the interstitium. In the brain, BUS caused meningeal thickening by congestion and hemorrhage, and degeneration of hippocampal neurons and Purkinje cells in the cerebellum as well as other brain areas. Against BUS, QCT markedly alleviated most liver damages, and BPP was seen to aggravate nuclear enlargement of hepatocytes, and fibroblastic proliferation and mononuclear infiltration in the portal areas. In the kidney, QCT did not affect BUS-induced pathological alterations. However, BUS+BPP and BUS+QCT+BPP group exhibited milder lesions. The three treatment regimens alleviated most brain lesions, with superior ameliorative effect in the BUS+QCT+BPP group. In conclusion, BUS damages the liver, kidney and brain in SD rats, and co-treatment of rats with BUS and QCT or BPP markedly alleviates most of the pathological lesions induced by BUS.