Reversal of cadmium-induced vascular dysfunction and oxidative stress by meso-2,3-dimercaptosuccinic acid in mice

Abstract

Cadmium (Cd) is a heavy metal which causes concern as an environmental toxicant. Therapy with chelating agents is considered to be the rational treatment against metal poisoning. This study was designed to evaluate whether meso-2,3-dimercaptosuccinic acid (DMSA) could alleviate oxidative stress and vascular dysfunction in mice with subchronic exposure to Cd. Male ICR mice received CdCl2 (100 mg/L) via drinking water for 8 weeks. After Cd exposure, DMSA at a dose of 25 mg/kg or 50 mg/kg was intragastrically administered once daily for 5 consecutive days at the end of Cd treatment. It was found that Cd-induced hypertension and markedly blunted vascular responses to vasoactive agents, including acetylcholine, phenylephrine and sodium nitroprusside. Treatment with DMSA significantly restored blood pressure and improved vascular responsiveness when compared with Cd-treated controls. Moreover, DMSA protected against Cd-induced severe oxidative stress by normalization of the redox ratios of glutathione to glutathione disulfide and suppression of plasma malondialdehyde, plasma protein carbonyl, urinary nitrate/nitrite, and superoxide production from thoracic aorta. DMSA partially reduced Cd contents in the blood, heart, liver and kidneys. In conclusion, our present study provides the first evidence of the therapeutic efficacy of DMSA against oxidative stress and vascular dysfunction in Cd-intoxicated mice.