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Protective effects of mefunidone on ischemia-reperfusion injury/Folic acid-induced acute kidney injury

Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Li, Jiajia;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Jiang, Yupeng;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Dai, Qin;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Yu, Yue;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Lv, Xin;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Zhang, Yan;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Liao, Xiaohua;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Ao, Liyun;
Affiliation
Department of Medicinal Chemistry ,Xiangya School of Pharmaceutical Sciences ,Central South University ,Changsha ,China
Hu, Gaoyun;
Affiliation
Hunan Key Lab of Organ Fibrosis ,Changsha ,China
Meng, Jie;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Peng, Zhangzhe;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Tao, Lijian;
Affiliation
Department of Nephrology ,Xiangya Hospital ,Central South University ,Changsha ,China
Xie, Yanyun

Renal ischemia-reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI). It poses a significant threat to public health, and effective therapeutic drugs are lacking. Mefunidone (MFD) is a new pyridinone drug that exerts a significant protective effect on diabetic nephropathy and the unilateral ureteral obstruction (UUO) model in our previous study. However, the effects of mefunidone on ischemia-reperfusion injury-induced acute kidney injury remain unknown. In this study, we investigated the protective effect of mefunidone against ischemia-reperfusion injury-induced acute kidney injury and explored the underlying mechanism. These results revealed that mefunidone exerted a protective effect against ischemia-reperfusion injury-induced acute kidney injury. In an ischemia-reperfusion injury-induced acute kidney injury model, treatment with mefunidone significantly protected the kidney by relieving kidney tubular injury, suppressing oxidative stress, and inhibiting kidney tubular epithelial cell apoptosis. Furthermore, we found that mefunidone reduced mitochondrial damage, regulated mitochondrial-related Bax/bcl2/cleaved-caspase3 apoptotic protein expression, and protected mitochondrial electron transport chain complexes III and V levels both in vivo and in vitro , along with a protective effect on mitochondrial membrane potential in vitro . Given that folic acid (FA)-induced acute kidney injury is a classic model, we used this model to further validate the efficacy of mefunidone in acute kidney injury and obtained the same conclusion. Based on the above results, we conclude that mefunidone has potential protective and therapeutic effects in both ischemia-reperfusion injury- and folic acid-induced acute kidney injury.

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License Holder: Copyright © 2022 Li, Jiang, Dai, Yu, Lv, Zhang, Liao, Ao, Hu, Meng, Peng, Tao and Xie.

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