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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 9251303, 12 pages
https://doi.org/10.1155/2017/9251303
Research Article

Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response

1Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA
2Department of Clinical Biochemistry, Christian Medical College, Vellore 632004, India
3Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA

Correspondence should be addressed to Partha Krishnamurthy; ude.cmuk@irutsakp

Received 15 September 2016; Revised 10 November 2016; Accepted 20 November 2016; Published 9 January 2017

Academic Editor: Rodrigo Franco

Copyright © 2017 Hemantkumar Chavan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.