Melatonin counteracts alterations in oxidative metabolism and cell viability induced by intracellular calcium overload in human leucocytes: Changes with age

Javier Espino, Ignacio Bejarano, Sergio D. Paredes, David González, Carmen Barriga, Russel J. Reiter, José A. Pariente, Ana B. Rodríguez

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Ageing is associated with an increased production of free radicals and alterations in the mechanisms of adaptation to oxidative stress. In fact, the free radical theory of ageing proposes that deleterious actions of free radicals are responsible for the functional deterioration associated with ageing. Moreover, a close relationship exists between calcium homeostasis and oxidative stress. The current work was aimed at proving that intracellular calcium overload induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and/or thapsigargin leads to oxidative stress. We additionally examined the effect of melatonin on the levels of reactive oxygen species (ROS) and cell viability in human leucocytes collected from young (20-30-year-old) and elderly (65-75-year-old) individuals under both basal and oxidative stress-induced conditions. Treatments with 10 nM FMLP and/or 1 μM thapsigargin induced a transient increase in cytosolic free-calcium concentration ([Ca 2+]c) in human leucocytes due to calcium release from internal stores, and led in turn to oxidative stress, as assessed by intracellular ROS measurement. Non-treated leucocytes from aged individuals exhibited higher ROS levels and lower rates of cell survival when compared to leucocytes from young individuals. Similar results were obtained in FMLP and/or thapsigargin-treated leucocytes from elderly individuals when compared to those from the young individuals. Melatonin treatment significantly reduced both hydrogen peroxide (H2O2) and superoxide anion levels, likely due to its free-radical scavenging properties, and enhanced leucocyte viability in both age groups. Therefore, melatonin may be a useful tool for the treatment of disease states and processes where an excessive production of oxidative damage occurs.

Original languageEnglish (US)
Pages (from-to)590-597
Number of pages8
JournalBasic and Clinical Pharmacology and Toxicology
Volume107
Issue number1
DOIs
StatePublished - Jul 2010

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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