Abstract
Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250–300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.
Highlights
Renal ischemia-reperfusion injury (RIRI) is the major contributor to acute kidney injury (AKI) in different clinical conditions, especially post-renal transplantation, vascular surgeries, trauma and partial nephrectomy [1]
Numerous studies have reported that Salvianolic acid B (SAB) shows positive results against the ischemic reperfusion (IR) model in different organs
Several studies confirm that SAB can substantially ameliorate renal function by lowering inflammation and oxidative stress via several signaling pathways [9,15,21]
Summary
Renal ischemia-reperfusion injury (RIRI) is the major contributor to acute kidney injury (AKI) in different clinical conditions, especially post-renal transplantation, vascular surgeries, trauma and partial nephrectomy [1]. Epidemiological studies indicate that AKI is strongly affiliated with high mortality and morbidity [2]. Pathophysiology of RIRI and subsequent AKI is not completely explored till today. Experimental data suggest that hypoxia, apoptosis, endothelial dysfunction, oxidative stress and inflammatory response play a pivotal role in renal dysfunction during ischemic reperfusion (IR) condition [3,4]. Oxidative stress and inflammation are interlinked and demonstrate to be the major contributors to RIRI [5,6].
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