Tetrahydrocurcumin in combination with deferiprone attenuates hypertension, vascular dysfunction, baroreflex dysfunction, and oxidative stress in iron-overloaded mice

摘要

Excessive iron can generate reactive oxygen species (ROS), leading to oxidative stress that is closely associated with cardiovascular dysfunction. Iron overload was induced in male ICR mice by injection of iron sucrose (10 mg/kg/day) for eight weeks. Iron overload was evidenced by increased serum iron indices. The mice developed increased blood pressure, impaired vascular function and blunted response of the autonomic nervous system. These effects were accompanied by increased malondialdehyde levels in various tissues, increased nitric oxide metabolites in plasma and urine, and decreased blood glutathione. Tetrahydrocurcumin (MU, 50 mg/kg/day), deferiprone (or L1, 50 mg/kg/day) or both was orally administered throughout the period of iron sucrose injection. The treatments significantly alleviated the deleterious cardiovascular effects of iron overload, and were associated with modulation of nitric oxide levels. An imbalance between endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) expression in response to iron overload was normalized by THU, L1 or the combination treatment. Moreover, the treatment decreased the upregulated expression levels of gp91(phox), p47(phox) and HO-1. The combination of THU and L1 exerted a greater effect than THU or L1 monotherapy. These results suggest beneficial effects of THU and L1 on iron-induced oxidative stress, hypertension, and vascular dysfunction. (C) 2016 Elsevier Inc. All rights reserved.