Department of Physiology, Faculty of Medicine, King AbdulAziz University, Jeddah, Saudi Arabia.
Eur Rev Med Pharmacol Sci. 2023 Feb;27(3):1155-1169. doi: 10.26355/eurrev_202302_31222.
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.
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.
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.
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.
高胆固醇血症（HC）是一种破坏性的代谢紊乱疾病，通过氧化应激和炎症对肾脏的功能和结构模式产生负面影响。本文旨在阐述类黄酮芹菜素（Apg）的作用，鉴于其抗氧化、抗炎和抗凋亡能力，可缓解高胆固醇血症引起的肾损伤。
将 24 只成年 Wister 雄性大鼠分为四组，连续 8 周进行治疗：对照组，给予正常颗粒饮食（NPD）；Apg 组，给予 NPD 和 Apg（50mg/Kg）；HC 组，给予富含 4%胆固醇和 2%胆酸钠的 NPD；HC/Apg 组，同时给予高胆固醇血症并给予 Apg 灌胃。实验结束时，采集血清样本以测量肾功能参数、血脂谱、MDA 和 GPX-1。然后，对肾脏进行组织学研究，并匀浆以通过 RT-qPCR 评估 IL-1β、IL-10 以及肾脏损伤分子-1（KIM-1）、纤连蛋白 1（Fn1）和核因子 E2 相关因子 2（Nrf2）的基因表达。
HC 扰乱了肾功能、血脂谱和血清氧化还原平衡。此外，HC 引起了促炎/抗炎失衡，上调了 KIM-1 和 Fn1，下调了肾脏组织的 Nrf2 基因表达。此外，HC 导致肾脏细胞结构的明显组织病理学变化。令人欣慰的是，在同时给予 Apg 补充高胆固醇饮食的情况下，HC/Apg 组的大多数肾功能、组织学和生物分子损伤都得到了恢复。
Apg 通过调节 KIM-1、Fn1 和 Nrf2 信号通路缓解 HC 引起的肾损伤，这一有前途的作用可能有助于作为抗高胆固醇血症药物的辅助手段，以治疗 HC 引起的破坏性肾脏并发症。
