Effect of Combined Tetrahydrocurcumin and Deferiprone on Oxidative Stress and Vascular Dysfunction in Iron Overloaded Mice
Abstract
Background and Objective: Iron overload is an excessive accumulation of iron in the body. This condition can generate reactive oxygen species (ROS), which leads to oxidative stress and subsequently vascular dysfunction via the mechanism of reducing nitric oxide (NO), a key regulator of vascular homeostasis. Deferiprone (or L1) is used to prevent iron toxicity by chelating labile iron. Moreover, several studies indicated that tetrahydrocurcumin (THU) possesses strong antioxidant and vasculoprotective effect in various stress conditions. The present study was aimed to investigate whether supplementation with L1 plus THU can mitigate oxidative stress and vascular dysfunction in iron overloaded mice, a model represented iron overload condition.
Methods: Iron sucrose (10 mg/kg/day, i.p.) was injected to Imprinting Control Regio (ICR) mice for 8 weeks. . L1 or THU at dose of 50 mg/kg/day was intragastrically administered through the period of iron overload induction. Blood pressure, vascular responsiveness to various vasoactive agents, lipid peroxidation markers were measured. The thoracic aortas were excised for assessment of superoxide radical (O2·-) production.
Results: Iron overloaded mice exhibited high arterial blood pressure and impaired vascular responses to vasoconstrictor and vasodilators, Increase in O2·- production in vascular tissues and plasma malondialdehyde (MDA) concentration were found in iron overloaded mice. Treatment with L1 or THU partially alleviated these deleterious effects. Interestingly, combined therapy with L1 and THU exerted a greater effect than L1 or THU monotherapy.
Conclusion: Iron overload-induced by iron sucrose enhanced oxidative stress and vascular dysfunction in mice. L1 plus THU restored the blood pressure, decreased oxidative stress, attenuated vascular dysfunction.
Key words: Iron overload, Oxidative stress, Vascular dysfunction, Deferiprone, Tetrahydrocurcumin
