Superior renoprotective effects of the combination of breviscapine with enalapril and its mechanism in diabetic rats

Abstract

Breviscapine is a flavonoid extracted from a Chinese herb Erigeron breviscapus, previously it was shown that treatment with breviscapine attenuated renal injury in the diabetic rats. The purpose of this study was to investigate whether breviscapine combined with enalapril (an ACE inhibitor) have superior renoprotective effects against diabetic nephropathy. Rats were randomly separated into five groups: control, diabetes, diabetes treated with enalapril, diabetes treated with breviscapine, or diabetes treated with combined enalapril with breviscapine. Twenty-four hours urinary AER and the levels of 3-NT in renal tissue and MDA in renal tissue and urine as well as activities and expression of PKC in renal tissue were determined, and renal tissue morphology were observed by light microscopy after 8 weeks. Expression of TGFβ1 protein was performed by immunohistochemistry method. Increased AER and kidney pathologic injury were attenuated by treatment with either enalapril or breviscapine and further reduced by the combination of the two. Elevated 3-NT in renal tissue and MDA levels in renal tissue and urine were reduced by enalapril or breviscapine and, more effectively, by combined enalapril with breviscapine. PKC activities and expression were higher in renal tissue in diabetic rats than those of the control group, which were reduced by both monotherapies, and further abrogated by combination therapy in both cases. Overexpression of TGFβ1 protein observed in the glomeruli and tubulointerstitium of diabetic rats was attenuated by enalapril or breviscapine to a similar lever and further reduced by the combination of the two. The combination of enalapril and breviscapine confers superiority over monotherapies on renoprotection, which mechanism may be at least partly correlated with synergetic suppression on increased oxidative stress and PKC activities as well as overexpression of TGFβ1 in renal tissue.

Keywords: 3-NT; 3-nitrotyrosine; A(G); A(M); ACE; AER; Angiotensin-converting enzyme; BW; Breviscapine; DN; Diabetic nephropathy; Enalapril; ICAM-1; KW; MCP-1; MDA; PKC; Protein kinase C; ROS; Reactive oxygen species; SABC; STZ; Streptavidin-biotin-peroxidase complex; TGFβ1; TII; Transforming growth factor β1; V(G); albumin excretion rate; body weight; diabetic nephropathy; glomerular cross-sectional area; glomerular volume; intercellular adhesion molecule-1; kidney weight; malondialdehyde; mesangial area; monocyte chemoattractant protein-1; protein kinase C; streptozotocin; transforming growth factor β1; tubulointerstital injury.