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Synergism between melatonin and atorvastatin against endothelial cell damage induced by lipopolysaccharide.

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.
AuthorsJosé C Dayoub, Francisco Ortiz, Luis C López, Carmen Venegas, Alberto Del Pino-Zumaquero, Olga Roda, Indalecio Sánchez-Montesinos, Darío Acuña-Castroviejo, Germaine Escames
JournalJournal of pineal research (J Pineal Res) Vol. 51 Issue 3 Pg. 324-30 (Oct 2011) ISSN: 1600-079X [Electronic] England
PMID21585521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2011 John Wiley & Sons A/S.
Chemical References
  • DNA Primers
  • Free Radicals
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipopolysaccharides
  • Pyrroles
  • RNA, Messenger
  • Reactive Oxygen Species
  • Atorvastatin
  • Nitric Oxide Synthase Type III
  • Melatonin
Topics
  • Atorvastatin
  • Base Sequence
  • Blotting, Western
  • Cells, Cultured
  • DNA Primers
  • Drug Synergism
  • Endothelium, Vascular (cytology, drug effects)
  • Free Radicals (metabolism)
  • Heptanoic Acids (pharmacology)
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
  • Lipid Peroxidation (drug effects)
  • Lipopolysaccharides (pharmacology)
  • Melatonin (pharmacology)
  • Nitric Oxide Synthase Type III (genetics, metabolism)
  • Oxidative Stress
  • Pyrroles (pharmacology)
  • RNA, Messenger (genetics)
  • Reactive Oxygen Species (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction

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