Omeprazole Alleviates Aristolochia manshuriensis Kom-Induced Acute Nephrotoxicity.

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

doi:10.1371/journal.pone.0164215

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.

Highlights

Aristolochia manshuriensis Kom (AMK), a member of the Aristolochiaceae family, has been used as an ingredient in herbal medicines to treat arthritis, hepatitis, rheumatism, pain, tussis, obesity and snake bites for thousands of years in China, Korea and Japan [1,2,3,4]
All mice in the 5.3 g/kg group died within 6 days after AMK administration, 37.5% mice in the 3.4 g/kg group died by day 8 after AMK administration, and the remaining mice survived to the endpoint of our study, i.e., day 14
When the mice were pretreated with OM 30 minutes before AMK intragastric gavage, there was a significant reduction in lethality in each treatment group (Fig 1C and 1D)

Summary

Introduction

Aristolochia manshuriensis Kom (AMK), a member of the Aristolochiaceae family, has been used as an ingredient in herbal medicines to treat arthritis, hepatitis, rheumatism, pain, tussis, obesity and snake bites for thousands of years in China, Korea and Japan [1,2,3,4]. Aristolochic acid (AA) is an active ingredient in Aristolochia and Asarum genera and is both nephrotoxic and carcinogenic [5,6,7,8,9]. Cytochrome P450 (CYP450) is the superfamily of enzymes that metabolize endogenous compounds and xenobiotics, including drugs, carcinogens, and environmental contaminants [11]. The CYP450 superfamily contains more than 50 isozymes, including CYP 1A1, CYP 1A2, PLOS ONE | DOI:10.1371/journal.pone.0164215. The CYP450 superfamily contains more than 50 isozymes, including CYP 1A1, CYP 1A2, PLOS ONE | DOI:10.1371/journal.pone.0164215 October 7, 2016

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Results

Discussion

Conclusion