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Abstract Title:

Targeting renal OATs to develop renal protective agent from traditional Chinese medicines: Protective effect of Apigenin against Imipenem-induced nephrotoxicity.

Abstract Source:

Phytother Res. 2020 May 28. Epub 2020 May 28. PMID: 32468621

Abstract Author(s):

Xiaokui Huo, Qiang Meng, Changyuan Wang, Jingjing Wu, Yanna Zhu, Pengyuan Sun, Xiaodong Ma, Huijun Sun, Kexin Liu

Article Affiliation:

Xiaokui Huo

Abstract:

Imipenem (Imp) is a widely used broad-spectrum antibiotic. However, renal adverse effects limit its clinical application. We previously reported that organic anion transporters (OATs) facilitated the renal transport of Imp and contributed its nephrotoxicity. Natural flavonoids exhibited renal protective effect. Here, we aimed to develop potent OAT inhibitors from traditional Chinese medicines (TCMs) and to evaluate its protective effect against Imp-induced nephrotoxicity. Among 50 TCMs, Tribuli Fructus, Platycladi Cacumen, and Lycopi Herba exhibited potent inhibition on OAT1/3. After screening their main components, Apigenin strongly inhibited Imp uptake by OAT1/3-HEK293 cells with IC50 values of 1.98± 0.36 μM (OAT1) and 2.29 ± 0.88 μM (OAT3). Moreover, Imp exhibited OAT1/3-dependent cytotoxicity, which was alleviated by Apigenin. Furthermore, Apigenin ameliorated Imp-induced nephrotoxicity in rabbits, and reduced the renal secretion of Imp. Apigenin inhibited intracellular accumulationof Imp and sequentially decreased the nephrocyte toxicity in rabbit primary proximal tubule cells (rPTCs). Apigenin, a flavone widely distributed in TCMs, was a potent OAT1/3 inhibitor. Through OAT inhibition, at least in part, Apigenin decreased the renal exposure of Imp and consequently protectedagainst the nephrotoxicity of Imp. Apigenin can be used as a promising agent to reduce the renal adverse reaction of Imp in clinic.

Study Type : Animal Study

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