Biomarkers of adverse response to mercury: histopathology versus thioredoxin reductase activity.

Vasco Branco,Cristina Carvalho,João Canário,Paula Ramos,Jun Lu,Arne Holmgren

doi:10.1155/2012/359879

Abstract

Exposure to mercury is normally assessed by measuring its accumulation in hair, blood or urine. Currently, the biomarkers of effect that have been proposed for mercurials, such as coproporphyrines or oxidative stress markers, are not sensitive enough and lack specificity. Selenium and selenoproteins are important targets for mercury and thioredoxin reductase (TrxR) in particular was shown to be very sensitive to mercury compounds both in vitro and in vivo. In this study we looked into the relation between the inhibition of thioredoxin reductase (TrxR) activity and histopathological changes caused by exposure to mercurials. Juvenile zeabra-seabreams were exposed to Hg2+ or MeHg for 28 days and histopathological changes were analyzed in the liver and kidney as well as TrxR activity. Both mercurials caused histopathological changes in liver and kidney, albeit Hg2+ caused more extensive and severe lesions. Likewise, both mercurials decreased TrxR activity, being Hg2+ a stronger inhibitor. Co-exposure to Hg2+ and Se fully prevented TrxR inhibition in the liver and reduced the severity of lesions in the organ. These results show that upon exposure to mercurials, histopathological alterations correlate with the level of TrxR activity and point to the potential use of this enzyme as a biomarker of mercury toxicity.

Highlights

Adverse health effects of mercury include neurotoxicity, nephrotoxicity, cardiotoxicity, teratogenicity and immunotoxicity
In this study we looked into the relation between the inhibition of thioredoxin reductase (TrxR) activity and histopathological changes caused by exposure to mercurials
Co-exposure to Hg2+ and Se fully prevented TrxR inhibition in the liver and reduced the severity of lesions in the organ. These results show that upon exposure to mercurials, histopathological alterations correlate with the level of TrxR activity and point to the potential use of this enzyme as a biomarker of mercury toxicity

Summary

Introduction

Adverse health effects of mercury include neurotoxicity, nephrotoxicity, cardiotoxicity, teratogenicity and immunotoxicity. Neurotoxic symptoms are the most visible aspect of mercury poisoning [1]. The liver and kidney accumulate high amounts of mercurials [2,3,4] that may impair their regular functioning. In the liver of animals exposed to high levels of mercurials, hepatocytes are frequently hypertrophied with large-size vacuoles and widespread areas of necrosis can often be observed [3, 9]. The proximal tubule is the kidney structure most affected by mercurials; the cellular changes include swelling of the mitochondrial matrix and endoplasmatic reticulum, loss of membrane integrity and eventual cellular necrosis [10]. Nephrotoxicity caused by to Hg2+ accumulation, is well recognized but may arise from MeHg exposure [10, 11]

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