Marcela Rodrigues Moreira Guimarães

Melatonin reduces endoplasmic reticulum stress and autophagy in liver of leptin‐deficient mice

The sedentary lifestyle of modern society along with the high intake of energetic food has made obesity a current worldwide health problem. Despite great efforts to study the obesity and its related diseases, the mechanisms underlying the development of these diseases are not well understood. Therefore, identifying novel strategies to slow the progression of these diseases is urgently needed. Experimental observations indicate that melatonin has an important role in energy metabolism and cell signalling; thus, the use of this molecule may counteract the pathologies of obesity. In this study, wild‐type and obese (ob/ob) mice received daily intraperitoneal injections of melatonin at a dose of 500 μg/kg body weight for 4 weeks, and the livers of these mice were used to evaluate the oxidative stress status, proteolytic (autophagy and proteasome) activity, unfolded protein response, inflammation and insulin signalling. Our results show, for the first time, that melatonin could significantly reduce endoplasmic reticulum stress in leptin‐deficient obese animals and ameliorate several symptoms that characterize this disease. Our study supports the potential of melatonin as a therapeutic treatment for the most common type of obesity and its liver‐associated disorders.

Overweight in elderly people induces impaired autophagy in skeletal muscle

Abstract Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged‐related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases. Graphical abstract Figure. No caption available. HighlightsOverweight induces oxidative and endoplasmic reticulum stress in the elderly.Aging aggravates overweight effect on human skeletal muscle.Overweight forces the aged muscle to increase requirements from autophagy mechanisms.Impaired autophagy could be the main reason of myogenesis dysfunction during aging.Overweight seems to promote pro‐inflammatory instead of anti‐inflammatory response.

Alpha-tocopherol in the brain tissue preservation of stroke-prone spontaneously hypertensive rats

Oxidative stress has an important role in neuronal damage during cerebral ischemia and can lead to cognitive and behavioral impairment. Alpha-tocopherol, a powerful antioxidant, may be able to preserve neuronal tissue and circumvent neurological deficits. Thus, this study aimed to investigate the influence of alpha-tocopherol in the preservation of brain tissue and the maintenance of memory formation in stroke-prone spontaneously hypertensive rats (SHRSP). To achieve this aim, twenty-four 15-week-old male SHRSP rats were separated into the following four groups (n = 6 each) that received different treatments over a 4-week period: the alpha-tocopherol group, the control group, the L-NAME group, and the L-NAME + alpha-tocopherol group. We evaluated the physiological parameters (body weight, diuresis, and food and water intake), an oxidative stress marker (malondialdehyde levels), and neurological responses (the Morris Water Maze and Novel Objects Recognition tests). Afterwards, the brains were removed for histopathological analysis and quantification of the number of cells in the hippocampus. Statistically, the alpha-tocopherol group demonstrated better results when compared to all groups. The data indicated a reduction in oxidative stress and the preservation of neurological responses in groups treated with alpha-tocopherol. In contrast, the L-NAME group exhibited increased malondialdehyde levels, impairment of neurological responses, and several hippocampus tissue injuries. The others groups exhibited nerve tissue changes that were restricted to the glial nodes. No significant alterations were observed in the physiologic parameters. Based on these findings, we suggest that alpha-tocopherol can prevent stroke, preserve the structure of the hippocampus, and maintain both memory and cognition functions.

Análise de idosos ambulatoriais quanto ao estado nutricional, sarcopenia, função renal e densidade óssea

Objectives : To evaluate relationships between nutritional status, sarcopenia and osteoporosis in older women.Subjects and methods : We studied 44 women, 67-94 years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73 m2, body mass index (BMI), arm circumference and calf (CP and CB), bone mineral density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia: IMM MM = MSS + MIS/height2. We used the Pearson correlation coefficient, p < 0.05 as significant.Results : MNA and IMM were positively correlated with BMI, CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen had a history of osteoporotic fractures. The lowest T-score was directly related to MAN and MG.Conclusions The aging caused the decline of FG, fat mass and muscle; the calf circumference, and brachial reflected nutritional status and body composition; and major influences on BMD were nutritional status and fat mass.Arq Bras Endocrinol Metab. 2014;58(3):226-31

Effects of alpha-tocopherol associated with lovastatin on brain tissue and memory function in SHRSPs

Strokes are preceded by oxidative stress and inflammation, two processes linked to atherosclerosis and hypertension. Statins have been widely employed to control atherosclerosis; however, there could be neurological implications to its use—including cognitive impairment. Thus,we aimed to determine whether alpha-tocopherol is capable of reversing the neurological side effects of statins and enhancing its anti-inflammatory properties. To assess these effects, 15-week-old stroke-prone spontaneously hypertensive rats (SHRSPs) were divided into four groups (n = 6, each): alpha-tocopherol (AT), lovastatin (LoV), alpha-tocopherol + lovastatin (AT + LoV), and control (C).We administered 120 IU of alpha-tocopherol diluted in 0.1 ml of coconut oil,whereas the dose of lovastatin was administered at a ratio of 1 mg/kg of rat body weight. The control group received 0.1 ml coconut oil. All animals received the treatments via orogastric gavage.We assessed body weight, diuresis, food and water intake, oxidative stress (malondialdehyde levels), the total cellular injury marker (lactate dehydrogenase), short and long-term memory, cognition, and histopathological changes in the hippocampus. The results demonstrated that lovastatin treatment did not negatively affect the memory of our animal model. In fact, the animals treated with AT and LoV showed improvement in memory and cognition. Additionally, both treatments decrease lactate dehydrogenase and oxidative stress levels. Furthermore, our study also demonstrated hippocampal tissue preservation in the treated groups.

Alpha‐tocopherol protects against memory impairment caused by L‐NAME and modulates the injury marker and blood coagulant parameters

Cerebrovascular disease studies have shown similarity between humans and spontaneously hypertensive rats stroke-prone rats in the development of spontaneous stroke and transitory ischemic attacks (TIA). In addition, nitric oxide (NO) suppression by L-arginine methyl ester (L-NAME) can precipitate several vascular diseases including TIA and strokes. On the other hand, alpha-tocopherol (AT) has been associated with beneficial effects on vascular disorders. Four groups were tested to evaluate AT effects on NO inhibition: AT, control (C), AT + L-NAME, and L-NAME. During 4 weeks, all groups had their physiologic parameters evaluated and were submitted to neurological tests. After the sacrifice of the animals, total L-lactate dehydrogenase, fibrinogen levels, and platelet counts were measured. Our results demonstrated improvement in memory function and sensory-motor function of the rats treated with AT. The AT treatment also demonstrated a significant difference on the injury identifier, fibrinogen levels, and platelet count between the treated groups and the L-NAME group. In conclusion, AT reversed damaging L-NAME neurological effects and could be considered as a possible protective agent in neurological diseases.

Effects of Vitamin K1 Supplementation on the Risk Factors to the Stroke and on Memory in Spontaneously Hypertensive Rats Stroke Prone (SHR-sp)

A number of risk factors have been associated to the stroke and many strategies have been proposed in order to control them as well. Vitamin K has been largely found in brain, which suggests a possible function at that tissue. This study aimed to evaluate the potential of this vitamin on the prevention of risk factors to stroke and on cognitive function on SHRSP rats. Twelve SHRSP males, 15 weeks old, were divided into two groups (n= 6 each), receiving the vehicle-coconut oil (control group) or 40 μg of phylloquinone (treated group) during 28 days. Biological parameters, systolic blood pressure and lipid profile were evaluated. Both groups were submitted to the neurological tasks. The data was treated by Students t test and ANOVA one-way test being P<0.05 considered significant. The phylloquinone supplementation showed a statistically significant reduction in the treated group of all parameters of lipid profile and systolic blood pressure when compared to the control group. Neurological evaluation indicated a statistically significant improvement in the performance of long term memory tests in the treated group, without similar findings in the evaluation of short memory. In sum, phylloquinone supplementation was shown to modulated lipid profile and protect neuronal suffering in this model.