Apigenin ameliorates hypercholesterolemic-induced kidney injury via modulating renal KIM-1, Fn1, and Nrf2 signaling pathways.

ABSTRACT

OBJECTIVE: Hypercholesterolemia (HC) is a devastating metabolic disorder that has a negative effect on the kidneys' functional and structural modalities via oxidative stress and inflammation. The aim of this paper is to elaborate on the role of the flavonoid apigenin (Apg), considering its antioxidant, anti-inflammatory, and antiapoptotic capabilities, in alleviating hypercholesterolemic-induced kidney injury. MATERIALS AND METHODS: Twenty-four adult Wister male rats were allocated into four equal groups and treated for eight consecutive weeks a control group, supplemented with a normal pellet diet (NPD); the Apg group, supplemented with NPD and Apg (50 mg/Kg); the HC group, fed with NPD enriched with 4% cholesterol and 2% sodium cholate; and the HC/Apg group, concomitantly rendered hypercholesterolemic and gavaged with Apg. At the end of the experiment, serum samples were collected to measure renal function parameters, lipid profile, MDA, and GPX-1. Thereafter, the kidneys were processed for histological study and homogenized to assess IL-1ß, IL-10, and the gene expression of kidney injury molecule-1 (KIM-1), fibronectin 1 (Fn1), and NF-E2-related factor 2 (Nrf2) via RT-qPCR. RESULTS: HC disturbed the renal function, lipid profile, and serum redox balance. In addition, HC elicited a proinflammatory/anti-inflammatory imbalance, upregulating KIM-1 and Fn1 and downregulating the Nrf2 gene expression of the kidney tissue. Moreover, HC induced marked histopathological changes in the kidney cytoarchitecture. Efficaciously, upon concomitant Apg supplementation with a high-cholesterol diet, most functional, histological, and biomolecular impairments of the kidney were comparatively restored in the HC/Apg group. CONCLUSIONS: Apg mitigated HC-induced kidney injury via modulating the KIM-1, Fn1, and Nrf2 signaling pathways, a promising effect that may be useful as an adjunct to antihypercholesterolemic medications to treat the devastating renal complications of HC.