Abstract
OBJECTIVE: Hypercholester-olemia (HC) is a devastating metabolic disor-der 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 apigen-in (Apg), considering its antioxidant, anti-inflam-matory, and antiapoptotic capabilities, in alleviat-ing 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 nor-mal pellet diet (NPD); the Apg group, supplement-ed 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, con-comitantly 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 his-tological study and homogenized to assess IL-1 beta, IL-10, and the gene expression of kidney in-jury molecule-1 (KIM-1), fibronectin 1 (Fn1), and NF-E2-related factor 2 (Nrf2) via RT-qPCR. RESULTS: HC disturbed the renal function, lip-id profile, and serum redox balance. In addition, HC elicited a proinflammatory/anti-inflammatory imbal-ance, upregulating KIM-1 and Fn1 and downregu-lating the Nrf2 gene expression of the kidney tis-sue. Moreover, HC induced marked histopatholog-ical changes in the kidney cytoarchitecture. Effica-ciously, upon concomitant Apg supplementation with a high-cholesterol diet, most functional, histo-logical, 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 antihypercholes-terolemic medications to treat the devastating renal complications of HC.