Synergism between melatonin and atorvastatin against endothelial cell damage induced by lipopolysaccharide
Article first published online: 17 MAY 2011
© 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 51, Issue 3, pages 324–330, October 2011
How to Cite
Dayoub, J. C., Ortiz, F., López, L. C., Venegas, C., del Pino-Zumaquero, A., Roda, O., Sánchez-Montesinos, I., Acuña-Castroviejo, D. and Escames, G. (2011), Synergism between melatonin and atorvastatin against endothelial cell damage induced by lipopolysaccharide. Journal of Pineal Research, 51: 324–330. doi: 10.1111/j.1600-079X.2011.00892.x
- Issue published online: 20 SEP 2011
- Article first published online: 17 MAY 2011
- Accepted manuscript online: 18 APR 2011 03:19AM EST
- Received January 20, 2011; Accepted April 8, 2011.
- endothelial nitric oxide synthase;
- human umbilical vein endothelial cells;
- oxidative stress
Abstract: The beneficial effects of atorvastatin are based on both cholesterol-dependent and independent mechanisms. The latter probably include the ability of the estatin to enhance the expression of endothelial nitric oxide synthase (eNOS) and to cause a vasodilatation. In turn, the antioxidant and anti-inflammatory actions of melatonin are related to its vascular protection. In the present study, we investigated the efficacy of the combination of melatonin plus atorvastatin against endothelial cell damage induced by inflammation and oxidative stress injury. Human umbilical vein endothelial cells (HUVEC) were cultured with bacterial lipopolysaccharide (LPS) in the presence or absence of melatonin and/or atorvastatin. LPS inhibited eNOS mRNA and protein expression, which was reversed by atorvastatin and, to a lesser extent, by melatonin. Together, melatonin + atorvastatin induced higher eNOS protein expression than either compound alone. Melatonin, but not atorvastatin, reduced free radical generation, lipid peroxidation, and interleukin-6 levels induced by LPS. In the presence of atorvastatin, the effects of melatonin were maintained or even improved. These data suggest that melatonin improves the beneficial effects of atorvastatin and reduces its side effects in endothelial cells during inflammation and under conditions of oxidative stress.