Decreased plasma thiol antioxidant capacity precedes neurological signs in a rat methylmercury intoxication model.

ABSTRACT

The main target organ for MeHg is the nervous system, and its neurological dysfunction remains irreversible. Therefore, predictive biomarkers associated with individual susceptibility to MeHg and future clinical severity are needed to protect against the progression of MeHg toxicity. In this study, we demonstrated that plasma thiol antioxidant capacity (-SHp) is a useful predictive biomarker associated with future clinical severity using MeHg-intoxicated rats administered 1 mg/kg/day for 4 weeks. Blood samples were collected from the subclavian vein of each rat once a week to examine total blood mercury concentrations and the levels of plasma oxidative stress markers. Time course analyses of the correlation between these weekly blood examination values and hind limb crossing signs score after 4 weeks of MeHg exposure were performed, and plasma -SHp levels after 2 weeks of MeHg exposure showed strong correlations with future hind limb crossing sign scores. Neuropathological changes also developed in parallel with hind limb crossing sign scores. Quantitative analysis of vacuolar areas in the spinal cord showed a strong correlation with hind limb crossing sign scores. In conclusion, evaluation of plasma -SHp levels allowed us to detect individuals at risk for health damage and could protect the sensitive population against MeHg toxicity.