Biomarkers of adverse response to mercury: histopathology versus thioredoxin reductase activity.
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 Hg(2+) 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 Hg(2+) caused more extensive and severe lesions. Likewise, both mercurials decreased TrxR activity, being Hg(2+) a stronger inhibitor. Co-exposure to Hg(2+) 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.
Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Avenue Professor Gama Pinto, 1649-003 Lisbon, Portugal.
Vasco
V
Branco
Paula
P
Ramos
João
J
Canário
Jun
J
Lu
Arne
A
Holmgren
Cristina
C
Carvalho
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D009928:Organ Specificity / Q000187:drug effects; D021541:Sea Bream / Q000378:metabolism*; D012643:Selenium / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
D015415:Biomarkers; D013880:Thioredoxin-Disulfide Reductase; D008628:Mercury; D012643:Selenium