Troxerutin alleviates kidney injury in rats via PI3K/AKT pathway by enhancing MAP4 expression.

Abstract

BackgroundTroxerutin is a flavonoid compound and possesses potential anti-cancer, antioxidant, and anti-inflammatory activities. Besides, cisplatin is one of the most widely used therapeutic agents, but the clinical uses of cisplatin are often associated with multiple side effects, among which nephrotoxicity is more common.Objective and designThis study explored the protective effects of troxerutin (150 mg kg−1 day−1 for 14 days) against cisplatin-induced kidney injury and the potential mechanism using Wistar rats as an experimental mammalian model.ResultsWe discovered that troxerutin could significantly alleviate cisplatin-induced renal dysfunction, such as increased levels of blood urea nitrogen and creatinine (P < 0.01), as well as improved abnormal renal tissue microstructure and ultrastructure. Additionally, troxerutin significantly decreased malondialdehyde (MDA), hydrogen peroxide (H2O2), NO, inducible nitric oxide synthase (iNOS) levels (P < 0.01), p-NF-κB p65/NF-κB p65, TNF-α, Pro-IL-1β, IL-6, B cell lymphoma-2 (Bcl-2)/Bcl-xl associated death promoter (Bad), Cytochrome C (Cyt C), Cleaved-caspase 9, Cleaved-caspase 3, and Cleaved-caspase 8 protein levels (P < 0.01) in the kidney tissues of cisplatin-treated rats; and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total antioxidant capacity (T-AOC) activities (P < 0.01), IL-10, Bcl-2 protein levels (P < 0.01).ConclusionThese results suggested that the underlying mechanism might be attributed to the regulation of Phosphoinositide 3 kinase/Protein kinase B (PI3K/AKT) pathway via enhancing MAP4 expression to attenuate cellular apoptosis, alleviating oxidative stress and inflammatory response.