Arsenic and Mercury Containing Traditional Chinese Medicine (Realgar and Cinnabar) Strongly Inhibit Organic Anion Transporters, Oat1 and Oat3,In Vivoin Mice

Wen-Hao Yu,Jin-Feng Qi,Mei Lin,Na Zhang,Chen Sun,Yong-Hui Wang

doi:10.1155/2015/863971

Abstract

Toxic heavy metals, including mercury (Hg) and arsenic (As), accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3, in vivo in mice kidney. Mice (n = 10) were orally treated with investigational samples. After last administration, all mice were i.v. p-aminohippuric acid (PAH), and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (p < 0.05), PAH accumulations in the kidney tissues were significantly higher (p < 0.05), PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar) probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3).

Highlights

Drug transporters are known to have a significant impact on the absorption, distribution, elimination, and toxicity of a large number of drugs [1]
It is noteworthy that organic anion transporters (OATs) which are the members of Solute Carrier Family 22 (SLC22) play a pivotal role in renal excretion of water-soluble or negatively charged organic compounds and their metabolites
It is worth noting that the oral LD50 for Realgar (As) and Cinnabar (Hg) in mice is about 3200 mg/kg and 2678 mg/kg, but the oral LD50 for arsenic trioxide (As3+), Oat1-mRNA (%) Oat3-mRNA (%)

Summary

Introduction

Drug transporters are known to have a significant impact on the absorption, distribution, elimination, and toxicity of a large number of drugs [1]. It is noteworthy that organic anion transporters (OATs) which are the members of Solute Carrier Family 22 (SLC22) play a pivotal role in renal excretion of water-soluble or negatively charged organic compounds (including endogenous waste products, numerous drugs) and their metabolites. A substantial fraction of such compounds carries a net negative charge at physiological pH and is referred to as organic anions (OAs). PAminohippuric acid (PAH) which is known to interact with multiple basolateral transporters in proximal tubule cells is the prototypic substrate for what is frequently referred to as the “classic” process of renal organic anion secretion [3]. The overlapping substrate specificity and localization at the basolateral membrane of proximal tubules from Oat and Oat support the assumption that both transporters may play a principle role in the absorption of PAH and other OAs [5, 7]

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