Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging.

Abstract

This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals.

• Authors: Katherine Forman, Elena Vara, Cruz García, Roman Kireev, Sara Cuesta, Darío Acuña-Castroviejo, J A F Tresguerres
• Journal: Journal of pineal research (J Pineal Res) Vol. 49 Issue 3 Pg. 312-20 (Oct 2010) ISSN: 1600-079X [Electronic] England
• PMID: 20738757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Journal of Pineal Research © 2010 John Wiley & Sons A/S.

Chemical References

• Antioxidants
• Interleukin-1
• NF-kappa B p50 Subunit
• NF-kappa B p52 Subunit
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• heme oxygenase-2
• Melatonin

Topics

• Aging (drug effects, genetics, physiology)
• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects, genetics)
• Disease Models, Animal
• Heart (drug effects)
• Heme Oxygenase (Decyclizing) (genetics)
• Heme Oxygenase-1 (genetics)
• Interleukin-1 (genetics)
• Male
• Melatonin (pharmacology)
• Mice
• NF-kappa B p50 Subunit (genetics)
• NF-kappa B p52 Subunit (genetics)
• Nitric Oxide Synthase Type II (genetics)
• Nitric Oxide Synthase Type III (genetics)
• Oxidative Stress (drug effects, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics)