Melatonin reduces peroxynitrite-induced injury in aortic smooth muscle cells

Acta Pharmacol Sin. 2004 Feb;25(2):186-90.

Abstract

Aim: To study the protective role of melatonin (MT) in peroxynitrite-induced injury in cultured aortic smooth muscular cells (ASMC).

Methods: Peroxynitrite was synthesized chemically with a quenched flow reaction. Cells were exposed to peroxynitrite 500 micromol/L for 1 h in the absence or presence of various concentrations of MT 100, 300, and 500 micromol/L. Nitrotyrosine (NT), a specific "footprint"of peroxynitrite formation, was detected by immunohistochemical technique. The DNA damage was assayed by TUNEL technique. The levels of MDA in the medium and cell viability were measured.

Results: Incubation of ASMC with peroxynitrite 500 micromol/L for 1 h elicited the increase in the extent of immunostaining for NT, the rate of the TUNEL-positive cell, the content of MDA in the medium, and the number of dead cell. Pretreatment of ASMC with MT 100-500 micromol/L decreased these peroxynitrite-induced changes in a concentration-dependent manner.

Conclusion: MT attenuated the injury induced by peroxynitrite in ASMC.

MeSH terms

  • Animals
  • Aorta / cytology
  • Cell Survival / drug effects
  • Cells, Cultured
  • DNA Damage / drug effects*
  • Free Radical Scavengers / pharmacology
  • Malondialdehyde / metabolism
  • Melatonin / pharmacology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / metabolism*
  • Peroxynitrous Acid / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism*

Substances

  • Free Radical Scavengers
  • Peroxynitrous Acid
  • 3-nitrotyrosine
  • Tyrosine
  • Malondialdehyde
  • Melatonin