Gossypetin mitigates doxorubicin-induced nephrotoxicity: A histopathological and biochemical evaluation

Abstract

Doxorubicin (DOX) is an anticancer agent that is generally used to treat wide range of malignancies. Gossypetin (GTIN) is a well-known bioflavonoid that shows multiple therapeutical potentials. The experiment aimed toelucidate the nephroprotective impact of GTIN against renal damage caused by DOX. 24 Sprague-Dawley (SD) rats were separated into 4 groups: Control, DOX (3 mg/kg i.p.), DOX + GTIN (3 mg/kg i.p. + 30 mg/kg by oral gavage), and GTIN (30 mg/kg. orally) for the evaluation of renal markers, apoptotic markers, antioxidant and inflammatory profile. The outcomes of the experiment apprised that DOX exposure induced a pronounced decrease in enzymatic activities of antioxidants including glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), glutathione-S-transferase (GST) as well as glutathione (GSH) accompanied by an increment in reactive oxygen species (ROS) as well as malondialdehyde (MDA) levels. Likewise, DOX intoxication promoted escalation in the urea, kidney injury molecule-1 (KIM-1), creatinine, as well as neutrophil gelatinase-associated lipocalin (NGAL) level, on the other hand instigating a remarkable decline in creatinine clearance level. DOX induction brought a considerable escalation in interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa-B (NF-κB) as well as cyclooxygenase-2 (COX-2). In addition, DOX administration depicted a considerable raised in Caspase-9, Bax as well as Caspase-3 levels, while lowered Bcl-2 level. DOX treatment also prompted histomorphological impairment. GTIN + DOX co-treatment ameliorated all the above-stated damages in the kidneys. In conclusion, GTIN can effectively mitigate the renal impairments induced by DOX-prompted nephrotoxicity.