Curcumin Mitigates Hypertension, Endothelial Dysfunction and Oxidative Stress in Rats with Chronic Exposure to Lead and Cadmium

Tohoku J Exp Med. 2021 Jan;253(1):69-76. doi: 10.1620/tjem.253.69.

Abstract

Lead (Pb) and cadmium (Cd) are environmental pollutants and nonessential elements in the body. Both metals induce the development of hypertension which is associated with oxidative stress. Curcumin (CUR) is a polyphenolic compound with strong antioxidant activity. The present study evaluated the effect of CUR on oxidative stress, alteration of vascular responsiveness and hypertension induced by exposure to either Pb, Cd or the combination of Pb and Cd. Male Sprague-Dawley rats were exposed to low level of lead acetate (100 mg/L) and/or cadmium chloride (10 mg/L) in the drinking water for 16 weeks. The control animals received deionized water as drinking water. CUR (100 mg/kg) or propylene glycol as vehicle was intragastrically administered once daily for the last 4 weeks. Exposure to Pb, Cd or the combination induced increases in blood pressure and peripheral vascular resistance, and decreased the blood pressure response to intravenous infusion to acetylcholine. Supplementation with CUR significantly reduced blood pressure, alleviated oxidative stress, and increased plasma nitrate/nitrite and glutathione in the blood. The effects of CUR were associated with the improvement of vascular responsiveness, upregulation of the endothelial nitric oxide synthase and downregulation of the NADPH oxidase expression. Furthermore, CUR reduced the metal levels in blood, aorta, liver and kidney. Altogether, exposure to the combination of Pb and Cd aggravated hypertension and oxidative stress, and CUR effectively ameliorated these adverse events in metal exposed animals. Data indicate that CUR may be useful as a dietary supplement for protection against the noxious effects of the heavy metals.

Keywords: cadmium; curcumin; hypertension; lead; oxidative stress.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / physiopathology
  • Blood Pressure / drug effects
  • Cadmium / toxicity*
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / physiopathology*
  • Hemodynamics / drug effects
  • Hypertension / drug therapy*
  • Hypertension / physiopathology*
  • Lead / toxicity*
  • Metabolome
  • NADPH Oxidase 2 / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type III / metabolism
  • Oxidative Stress* / drug effects
  • Plethysmography
  • Rats
  • Rats, Sprague-Dawley
  • Systole / drug effects

Substances

  • Cadmium
  • Lead
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • NADPH Oxidase 2
  • Curcumin