Melatonin supplementation over different time periods until ageing modulates genotoxic parameters in mice.

The ageing process is a multifactorial phenomenon, associated with decreased physiological and cellular functions and an increased propensity for various degenerative diseases. Studies on melatonin (N-acetyl-5-methoxytryptamine), a potent antioxidant, are gaining attention since melatonin production declines with advancing age. Hence, the aim of this study was to evaluate the effects of chronic melatonin consumption on genotoxic and mutagenic parameters of old Swiss mice. Herein, 3-month-old Swiss albino male mice (n = 240) were divided into eight groups and subdivided into two experiments: first (three groups): natural ageing experiment; second (five groups): animals that started water or melatonin supplementation at different ages (3, 6, 12 and 18 months) until 21 months. After 21 months, the animals from the second experiment were euthanized to perform the comet assay, micronucleus test and western blot analysis. The results demonstrated that melatonin prolonged the life span of the animals. Relative to genomic instability, melatonin was effective in reducing DNA damage caused by ageing, presenting antigenotoxic and antimutagenic activities, independently of initiation age. The group receiving melatonin for 18 months had high levels of APE1 and OGG1 repair enzymes. Conclusively, melatonin presents an efficient antioxidant mechanism aiding modulating genetic and physiological alterations due to ageing.

The role of exercise in brain DNA damage.

Cells are constantly subjected to cytotoxic and genotoxic insults resulting in the accumulation of unrepaired damaged DNA, which leads to neuronal death. In this way, DNA damage has been implicated in the pathogenesis of neurological disorders, cancer, and aging. Lifestyle factors, such as physical exercise, are neuroprotective and increase brain function by improving cognition, learning, and memory, in addition to regulating the cellular redox milieu. Several mechanisms are associated with the effects of exercise in the brain, such as reduced production of oxidants, up-regulation of antioxidant capacity, and a consequent decrease in nuclear DNA damage. Furthermore, physical exercise is a potential strategy for further DNA damage repair. However, the neuroplasticity molecules that respond to different aspects of physical exercise remain unknown. In this review, we discuss the influence of exercise on DNA damage and adjacent mechanisms in the brain. We discuss the results of several studies that focus on the effects of physical exercise on brain DNA damage.

2-methoxy-isobutyl-isonitrile-conjugated gold nanoparticles improves redox and inflammatory profile in infarcted rats.

The tissue response to acute myocardial infarction (AMI) is key to avoiding heart complications due to inflammation, mitochondrial dysfunction, and oxidative stress. Antioxidant and anti-inflammatory agents can minimize the effects of AMI. This study investigated the role of 2-methoxy-isobutyl-isonitrile (MIBI)-associated gold nanoparticles (AuNP) on reperfusion injury after ischemia and its effect on cardiac remodeling in an experimental AMI model. Three-month-old Wistar rats were subjected to a temporary blockade of the anterior descending artery for 30 min followed by reperfusion after 24 h and 7 days by intraventricularly administering 0.4, 1.3, and 3 mg/kg AuNP-MIBI. The cardiac toxicity and renal and hepatic function levels were determined, and the infarct and peri-infarct regions were surgically removed for histopathology, analysis of inflammation from oxidative stress, and echocardiography. MIBI-conjugated AuNP promoted changes in oxidative stress and inflammation depending on the concentrations used, suggesting promising applicability for therapeutic purposes.

Aerobic and strength training induce changes in oxidative stress parameters and elicit modifications of various cellular components in skeletal muscle of aged rats.

Skeletal muscle aging is associated with loss of mass, function, and strength-a condition known as sarcopenia. It has been reported that sarcopenia can be attenuated by physical exercise. Therefore, we investigated whether 2 different physical exercise protocols could modulate and induce changes in oxidative and inflammatory parameters, as well as in BDNF and DNA repair enzyme levels in skeletal muscle tissue of aged rats. Aging Wistar rats performed treadmill or strength training for 50 min 3 to 4 times a week for 8 weeks. Strength training decreased 2',7'-dichlorofluorescein (DCFH) oxidation (P = 0.0062); however, nitric oxide, protein deglycase DJ-1, and tumor necrosis factor alpha (TNF-α) levels increased after aerobic training (P = 0.04, P = 0.027 and P = 0.009, respectively). Both exercise protocols increased superoxide dismutase (SOD) and catalase (CAT) activity (P = 0.0017 and P = 0.0326) whereas the activity of glutathione (GSH) (P = 0.0001) was decreased. Brain-derived neurotropic factor (BDNF) levels were not affected by exercise, but 8-oxoguanine glycosylase (OGG1) decreased after strength training (P = 0.0007). In conclusion, oxidative parameters showed that skeletal muscle adapt to increased ROS levels, reducing the risk of free radical damage to the tissue after both exercise protocols. These results show that the effects of physical exercise on skeletal muscle are mediated in an exercise type-dependent manner.

Strength and Aerobic Exercises Improve Spatial Memory in Aging Rats Through Stimulating Distinct Neuroplasticity Mechanisms.

Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks. Spatial memory and neurotrophic and glutamatergic signaling in the hippocampus of aged rats were evaluated after aerobic or strength training. Both aerobic and strength training improved cognition during the performance of a spatial memory task. Remarkably, the improvement in spatial memory was accompanied by an increase in synaptic plasticity proteins within the hippocampus after exercise training, with some differences in the intracellular functions of those proteins between the two exercise protocols. Moreover, neurotrophic signaling (CREB, BDNF, and the P75NTR receptor) increased after training for both exercise protocols, and aerobic exercise specifically increased glutamatergic proteins (NMDA receptor and PSD-95). We also observed a decrease in DNA damage after aerobic training. In contrast, strength training increased levels of PKCα and the proinflammatory factors TNF-α and IL-1ß. Overall, our results show that both aerobic and strength training improved spatial memory in aging rats through inducing distinct molecular mechanisms of neuroplasticity. Our findings extend the idea that exercise protocols can be used to improve cognition during aging.

Effects of phonophoresis with gold nanoparticles on oxidative stress parameters in a traumatic muscle injury model.

The aim of this study was to evaluate the effects of therapeutic pulsed ultrasound with gold nanoparticles on oxidative stress parameters after traumatic muscle injury in Wistar rats. The animals were randomly divided into nine groups (n = 6 each): sham (uninjured muscle); muscle injury without treatment; muscle injury and treatment with dimethyl sulfoxide (15 mg/kg); muscle injury and treatment with gold nanoparticles (27 µg); muscle injury and treatment with dimethyl sulfoxide + gold nanoparticles (Plus); muscle injury and therapeutic pulsed ultrasound; muscle injury and therapeutic pulsed ultrasound + dimethyl sulfoxide; muscle injury and therapeutic pulsed ultrasound + gold nanoparticles; and muscle injury and therapeutic pulsed ultrasound + Plus. Gastrocnemius injury was induced by a single-impact blunt trauma. Therapeutic pulsed ultrasound (6-min application, frequency 1.0 MHz, intensity 0.8 W/cm(2)) was used 2, 12, 24, and 48 h after trauma. Mitochondrial superoxide generation, lipid peroxidation, and protein carbonylation, and the activities of superoxide dismutase, glutathione peroxidase, and catalase were evaluated. The increase in the superoxide production and TBARS and carbonyl levels observed in the control group after muscle damage were reduced in animals exposed to therapeutic pulsed ultrasound plus nanoparticles. Similarly, antioxidants enzymes showed a decreased activity with the same treatment. Our work suggest that therapeutic pulsed ultrasound + dimethyl sulfoxide + gold nanoparticles has beneficial effects on the muscle healing process by inducing a decrease in oxidative stress parameters and most likely decreasing the deleterious effects of the inflammatory response.