Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury

Salvatore Cuzzocrea, Russel J Reiter

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants (such as peroxynitrite) as mediators of inflammation, shock and ischemia/reperfusion injury. The aim of this review is to describe recent developments in the field of oxidative stress research. The first part of the review focuses on the roles of reactive oxygen species in shock, inflammation and ischemia/reperfusion injury. The second part of the review described the pharmacological action of melatonin in shock, ischemia/reperfusion, and inflammation. (1) The role of reactive oxygen species: Immunohistochemical and biochemical evidence demonstrate the production of reactive oxygen species in shock, inflammation and ischemia/reperfusion injury. Reactive oxygen species can initiate a wide range of toxic oxidative reactions. These include the initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3phosphate dehydrogenase, inhibition of membrane sodium/potassium ATP-ase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock, inflammation and ischemia and reperfusion. (2) Treatment with melatonin has been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock, inflammation and ischemia/reperfusion injury. Reactive oxygen species (e.g., superoxide, peroxynitrite, hydroxyl radical and hydrogen peroxide) are all potential reactants capable of initiating DNA single-strand breakage, with subsequent activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. Recently, it has been demonstrated that melatonin inhibits the activation of poly (ADP-ribose) synthetase, and prevents the organ injury associated with shock, inflammation and ischemia and reperfusion.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalEuropean Journal of Pharmacology
Volume426
Issue number1-2
DOIs
StatePublished - Aug 24 2001
Externally publishedYes

Fingerprint

Melatonin
Reperfusion Injury
Shock
Pharmacology
Inflammation
Reactive Oxygen Species
Poly Adenosine Diphosphate Ribose
Reperfusion
Peroxynitrous Acid
Ischemia
Ligases
Superoxides
Hydroxyl Radical
Glyceraldehyde
Inflammation Mediators
Enzyme Activation
Sodium Channels
Poisons
Electron Transport
Ion Channels

Keywords

  • Free radical
  • Inflammation
  • Ischemia/reperfusion
  • Melatonin
  • Shock

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury. / Cuzzocrea, Salvatore; Reiter, Russel J.

In: European Journal of Pharmacology, Vol. 426, No. 1-2, 24.08.2001, p. 1-10.

Research output: Contribution to journalArticle

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