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.