Tetrahydrocurcumin Attenuates Hemodynamic Disturbance and Oxidative Stress in Rats Exposed to Low Levels of Cadmium and Lead

Abstract

Background and objective: It is well known that the exposure to high levels of cadmium (Cd) and lead (Pb) increases risk of cardiovascular diseases. However, the harmful effect on the cardiovascular system after chronic exposure to low levels of these metals has been less defined. Tetrahydrocurcumin (THU), one of the major metabolites of curcumin, possesses strong antioxidant activity. This study aimed to explore whether THU could improve hemodynamics, vascular function and alleviate the oxidative stress in rats chronically exposed to low levels of Cd and Pb.

Methods: Low doses of cadmium chloride (10 mg/L) and lead acetate (100 mg/L) were given via drinking water to male Sprague-Dawley rats for sixteen weeks. THU at 50 mg/kg was intragastrically administered once daily starting from the 12^th to 16^th week of the experiment. At the end of experiments, hemodynamic status, vascular responsiveness, protein expression of eNOS and NADPH oxidase, and oxidative stress markers were examined.

Results: Cd and Pb raised arterial blood pressure, reduced blood flow and vascular responsiveness. The vascular dysfunction was associated with enhanced vascular O₂^•- production and decreased eNOS expression. Up-regulation of vascular p47^phox suggested that NADPH oxidase is a major source of O₂^•- in the metal intoxicated condition. Interestingly, Cd combined with Pb exhibited a synergistic effect on these parameters.  THU improved vascular function by alleviating oxidative stress, decreasing O₂^•- production, suppressing p47^phox and increasing eNOS expression.

Conclusions: This study demonstrated that THU has the potential to preserve vascular function and mitigate oxidative stress induced by Cd and Pb in rats.