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Apigenin ameliorates hypercholesterolemic-induced kidney injury via modulating renal KIM-1, Fn1, and Nrf2 signaling
1Department of Physiology, Faculty of Medicine, King AbdulAziz University, Jeddah, Saudi Arabia. Salmaghrabe@kau.edu.sa.
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-1β, 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.
Insights
Apigenin (Apg) supplementation helped restore kidney function in rats with hypercholesterolemia (HC)-induced kidney injury. This flavonoid demonstrated antioxidant and anti-inflammatory effects, mitigating damage and improving biomarkers.
Area of Science:
- Biochemistry
- Nephrology
- Pharmacology
Background:
- Hypercholesterolemia (HC) is a metabolic disorder causing kidney damage through oxidative stress and inflammation.
- Apigenin (Apg), a flavonoid, possesses antioxidant, anti-inflammatory, and antiapoptotic properties.
- Understanding Apg's role in mitigating HC-induced kidney injury is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the protective effects of apigenin (Apg) against hypercholesterolemia (HC)-induced kidney injury.
- To evaluate Apg's impact on oxidative stress, inflammation, and specific kidney injury markers.
- To assess Apg's potential as an adjunct therapy for hypercholesterolemia-related renal complications.
Main Methods:
- Adult Wistar rats were divided into control, Apg, HC, and HC/Apg groups for an eight-week treatment period.
- Measurements included serum renal function, lipid profile, oxidative stress markers (MDA, GPX-1), and inflammatory cytokines (IL-1β, IL-10).
- Kidney tissues were analyzed for histopathology and gene expression of KIM-1, Fn1, and Nrf2.
Main Results:
- Hypercholesterolemia impaired renal function, altered lipid profiles, and disrupted redox balance.
- HC induced kidney inflammation, upregulated KIM-1 and Fn1, and downregulated Nrf2 expression, alongside histopathological damage.
- Apigenin supplementation in the HC/Apg group significantly restored kidney function, histology, and biomolecular markers compared to the HC group.
Conclusions:
- Apigenin effectively mitigated hypercholesterolemia-induced kidney injury in rats.
- Apg demonstrated protective effects by modulating KIM-1, Fn1, and Nrf2 signaling pathways.
- Apigenin shows promise as a supportive treatment for renal complications associated with hypercholesterolemia.
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