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Abstract Title:

Tanshinone IIA prevents acetaminophen-induced nephrotoxicity through the activation of the Nrf2-Mrp2/4 pathway in mice.

Abstract Source:

Environ Toxicol. 2022 Mar 3. Epub 2022 Mar 3. PMID: 35243748

Abstract Author(s):

Xiqian Zhang, Fangyi Long, Ruina Li, Yujie Yang, Ting Wang, Qin He, Min Xu, Ling Wang, Xuehua Jiang

Article Affiliation:

Xiqian Zhang

Abstract:

It's known that APAP overdose often leads to hepatotoxicity and nephrotoxicity. In the present study, we investigated the preventative effect of Tan IIA on APAP-induced nephrotoxicity. Mice were orally administrated with Tan IIA (10 or 30 mg/kg/day) for 1 week and subsequently gavaged with 200 mg/kg of APAP. Tan IIA reduced APAP-induced nephrotoxicity as evidenced by histopathological evaluation and serum creatinine levels. Tan IIA pretreatment promoted the efflux of the toxic intermediate metabolite N-acetyl-p-benzoquinone imine (NAPQI), thus reduced its injury to mouse kidney. After Tan IIA pretreatment, a remarkable increase in mRNA and protein expression of Nrf2 and its target genes Mrp2 and Mrp4 was observed in Nrf2mice kidneys, however, no obvious change of Mrp2 and Mrp4 mRNA and protein expression was detected in Nrf2mice kidneys. HK-2 cells were used for exploring the roles of Tan IIA in the Nrf2-MRPs pathway in vitro. Consistently, Tan IIA up-regulated the Nrf2-MRPs pathway and promoted the nuclear Nrf2 accumulation in HK-2 cells. Collectively, our findings suggested that Tan IIA facilitated the clearance of toxic intermediate metabolite NAPQI from the kidney through upregulation of the Nrf2-MRP2/4 pathway, thereby, performing preventive effects against APAP-induced nephrotoxicity.

Study Type : Animal Study

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