Evaluation of possible protective role of glabridin against gentamicin-instigated nephrotoxicity via attenuation of oxidative stress

Abstract

Glabridin (GB) is a natural dietary flavonoid of plant origin with excellent antioxidant properties. Gentamicin (GM) is an aminoglycoside antibiotic that can potentially cause renal toxicity. This investigation was intended to elucidate the attenuative effects of GB against GM-instigated nephrotoxicity. The entire experiment was carried out for a week on adult male albino rats (n = 24), which were randomly separated into 4 comparable groups that included Group I (0.9% physiological saline), group II (80 mg/kg of GM i.p.), group III (80 mg/kg; 50 mg/kg of GM + GB respectively), and group IV (50 mg/kg of GB orally). Biochemical analysis of antioxidant enzymes i.e., superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione reductase (GSR), Glutathione-S-transferase (GST), glutathione (GSH), reactive oxygen species (ROS), hydrogen peroxide (H2O2), thiobarbituric acid reactive substance (TBARS) level, renal serum neutrophil gelatinase-associated lipocalin (NGAL) as well as kidney injury molecule-1 (KIM-1) along with urinary profile (Albumin, creatinine, urea, urinary protein, urobilinogen, and creatinine clearance), inflammatory markers (nuclear factor (NF)-κB, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interleukin (IL)-6 as well as cyclo-oxygenase (COX)-2), apoptotic markers (Bax, Caspase-3 as well as Caspase-9), anti-apoptotic markers (Bcl-2) as well as histopathology of renal tissues, were analyzed. GM significantly reduced antioxidant enzymes activity, on the other hand, GM treatment substantially elevated the concentration of ROS, H2O2, TBARS, as well as induced abnormality in renal serum markers and urine profile, inflammatory markers, pro-apoptotic markers whereas, declined the level of anti-apoptotic markers and induced substantial histopathological damages. However, GB treatment potentially alleviated damages caused by GM. Conclusively, the intriguing outcomes of the investigation propose that GB effectively protects against GM-prompted nephrotoxicity, which may indicate its anti-oxidant, anti-apoptotic as well as anti-inflammatory potential.