Quercetin and bradykinin potentiating peptide protect against Busulfan induced liver and kidney damage in Sprague Dawley rats: an ultrastructural study.

Abstract

Busulfan (BUS), a chemotherapeutic agent used to treat chronic myeloid leukemia, is associated with hepatotoxicity and nephrotoxicity. This study used transmission electron microscope (TEM) to characterize BUS-induced ultrastructural alterations in the liver and kidney of rats, and to evaluate the protective effects of quercetin (QCT), bradykinin potentiating peptide (BPP) and their combination. To our knowledge, these ultrastructural changes have not been previously reported. Rats received two BUS doses (10 mg/kg b.w.) at a 21-day interval. BUS caused marked hepatic alterations, including mitochondrial swelling with loss of cristae, rough endoplasmic reticulum (RER) dilatation, sinusoidal endothelial cell damage and increased collagen synthesis. Renal changes included thrombotic microangiopathy affecting the glomerular capillary, thickened glomerular basement membranes, reactive changes of podocyte and parietal epithelial cells, mesangial cell proliferation, Bowman's space dilatation, and increased periglomerular collagen deposition. Concomitant treatment with QCT markedly reduced most hepatic alterations, whereas the BUS+BPP group exhibited comparatively limited protection. The combined QCT+BPP treatment produced the greatest hepatic protection. In the kidney, co-treatment with QCT partially ameliorated BUS-induced damage, while BUS+BPP and BUS+QCT+BPP restored ultrastructural features to near normal. In conclusions, these findings demonstrate that BUS induces marked ultrastructural injury in the liver and kidney, QCT, BPP, particularly in combination, provide substantial protection against these alterations.