Crocin reverses unilateral renal ischemia reperfusion injury-induced augmentation of oxidative stress and toll like receptor-4 activity

Abstract

Renal Ischemia (RI) usually develops as a secondary manifestation of hypertension, various cardiovascular disorders and renal transplantation. It exerts hypoxic oxidative stress to kidneys, together with stimulation of several immune-mediated inflammatory cascades. Such events eventually damage renal tubules and glomeruli, driving acute kidney injury (AKI) and ultimately, renal failure. Crocin; the main bioactive constituent of Crocus sativus extract has been reported to demonstrate numerous pharmacological merits. In the current study, unilateral renal ischemia reperfusion injury (URIRI) was induced in rats by unilateral clamping of the left renal pedicle for 45 min followed by 24 h of reperfusion. Daily pre-treatment with crocin (20 mg/kg, orally) for 7 days, significantly improved all signs of renal injury. Biochemically, kidney functions; including serum creatinine (Sr Cr), blood urea nitrogen (BUN), proteinuria and creatinine clearance (Cr Cl) significantly improved. Inflammatory biomarkers; serum lactate dehydrogenase (LDH) and kidney nitric oxide (Nos) contents significantly declined. Oxidant/antioxidant balance was significantly restored; manifested in recovery of renal superoxide dismutase (SOD) activity, glutathione (GSH) concentration, malondialdehyde (MDA) content and restoration of serum catalase activity. Kidney contents of inflammatory cytokine interleukin-6 (IL6) and toll-like receptors 4 (TLR4) significantly declined as well. Histopathologically, crocin pretreatment resulted in signs of improvement with minimal renal lesions with significant decrease in renal inflammatory cells count. In conclusion, crocin induced restoration of normal kidney functions is mediated through multiple mechanisms including mainly attenuation of oxidative stress and inflammation via down-regulation of renal TLR4 and IL6 expression.