Gum Acacia mitigates diclofenac nephrotoxicity by targeting monocyte chemoattractant protein-1, complement receptor-1 and pro-apoptotic pathways

摘要

Treatment of many inflammatory diseases involves a chronic use of NSAIDs in large doses increasing acute kidney injury risk. This study was designed to evaluate a potential renoprotective effect of Gum Acacia (GA) on diclofenac (DICF) induced nephrotoxicity. Six groups of rats were used: normal group; control group (deprived from water during week 13), DICF group (deprived from water during week 13 and injected DICF i.p. 15 mg/kg/12 h at days 4 through 6 of water deprivation days, GA groups (1, 2 or 3 g/kg/day in drinking water) for 12 weeks followed by water deprivation and DICF injection as described. Kidney function, oxidative stress and anti-oxidant biomarkers were measured. Interleukin-1 beta, IL-10, TNF-alpha, complement receptor (CR)-1, monocyte chemoattractant protein (MCP)-1 and caspase-3 were assessed. Kidney sections were scored for fibrosis, tubular injury and inflammatory cells. An elevation In renal biomarkers, inflammatory cytokines, malondialdehyde and apoptotic markers was observed after DICF injection (p < 0.001). Gum Acacia (mostly 3 g/kg) markedly reduced fibrosis, tubular injury, IL-1 beta, TNF-alpha, caspase-3 and MCP-1 levels (p < 0.01). It increased IL-10, antioxidant capacity, CR-1 level in the kidney (p < 0.001). Protective effect may be mediated by anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms besides interfering with monocytes and complement mediated tissue damage pathways.