Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

Lianmei Wang; Hongbing Zhang; Chunying Li; Yan Yi; Jing Liu; Yong Zhao; Jingzhuo Tian; Yushi Zhang; Xiaolu Wei; Yue Gao; Aihua Liang

doi:10.1371/journal.pone.0164215

Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity

PLoS One. 2016 Oct 7;11(10):e0164215. doi: 10.1371/journal.pone.0164215. eCollection 2016.

Authors

Lianmei Wang¹, Hongbing Zhang², Chunying Li¹, Yan Yi¹, Jing Liu¹, Yong Zhao¹, Jingzhuo Tian¹, Yushi Zhang¹, Xiaolu Wei¹, Yue Gao³, Aihua Liang¹

Affiliations

¹ Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
² State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Beijing Institute of Radiation Medicine, Beijing, China.

Abstract

Aristolochia manshuriensis Kom (AMK) is a member of the Aristolochiaceae family and is a well-known cause of aristolochic acid (AA) nephropathy. In this study, we investigated the potential of omeprazole (OM) to alleviate AMK-induced nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp 1a1/2 and renal Cyp 1a1 expression in rats, as well as CYP 1A1 expression in human renal tubular epithelial cells (HKCs). HKCs with ectopic CYP 1A1 expression were more tolerant to AA than the control cells. Therefore, OM may alleviate AMK-mediated acute nephrotoxicity through induction of CYP 1A1. We suggest that the coadministration of OM might be beneficial for reducing of AA-induced nephrotoxicity.

MeSH terms

Acute Disease / therapy*
Animals
Aristolochia / adverse effects*
Aristolochic Acids
Cytochrome P-450 CYP1A1 / metabolism
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Female
Humans
Kidney / drug effects
Kidney / metabolism
Kidney Diseases / drug therapy*
Kidney Diseases / metabolism
Liver / drug effects
Liver / metabolism
Liver / microbiology
Male
Mice
Mice, Inbred ICR
Omeprazole / pharmacology*
Rats
Rats, Sprague-Dawley

Substances

Aristolochic Acids
Cytochrome P-450 CYP1A1
Omeprazole

Grants and funding

This work was supported by National Science and Technology Major Project (Grant 2015ZX09501004); the funder conceived and designed the experiments, analyzed the data and wrote the manuscript; and by Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Project (Grant Z195); the funder performed the experiments, analyzed the data and wrote the manuscript.