Lucia Marques Vianna

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.

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.

Effectiveness of B vitamins on the control of hypertension and stroke events of SHRSP rats.

ABSTRACT. The spontaneously hypertensive stroke-prone rat (SHRSP) is a recognized animal model for the study of severe hypertension and stroke, being characterized by presenting an elevated tissue levels of free radicals. Therefore, this study has the main goal to identify the effect of B vitamins, closely associated to the control of oxidative stress, on SHRSP rats. After 10 days (baseline period), the animals, 18 SHRSP rats at 18 weeks of age, were divided into three groups with six rats treated with riboflavin (B2), six treated with pyridoxine (B6) plus folic acid (B9), and control. Body weight, water and food intake, diuresis, sensory-motor responses, and systolic blood pressure of all the rats were determined daily. Physical aspects of whole body (i.e., distribution and coloring of hair, skin and mucosa, and an eventual presence of bleeding, stains, cracks, or opacification) and behavior were equally monitored. The data were evaluated by ANOVA two-way and p < .05 was considered significant. The supraphysiologic doses did not cause toxic effects. There was a significant decrease of systolic blood pressure, homocysteine, and malondialdehyde (MDA) blood levels in animals under B vitamin supplementation. The treatment also inhibited the neurological signs of an ischemic attack (unbalance, ataxia, and convulsions). The findings reported here suggest that B vitamin therapy was effective for the control of systolic blood pressure and oxidative stress. Hence, it could be thought as one of the alternative therapies to prevent the occurrence of stroke.

The effects of supraphysiological supplementation of b-carotene in spontaneously hypertensive rats (SHR and SHR-sp)

OBJECTIVE To investigate the effect of administration of supraphysiological β carotene on biological, laboratory and histological parameters of spontaneously hypertensive rats prone to stroke (SHR-sp). METHODS we used 36 male rats divided into three groups, each containing 12 rats of the types Wistar SHR and SHR-sp, subdivided into six control animals and six animals treated with supraphysiological doses of β carotene for two ten-week periods, interspersed by a one-week interruption. We carried out daily physical examination and blood pressure assessment. We collected blood for measurement of serum malondialdehyde; the liver and carotid arteries were subsequently harvested for histological examination. RESULTS there was a temporary change in the color of hair, a significant decrease (p <0.0001) in blood pressure (20 mg β carotene supplementation) and serum levels of malondialdehyde (p<0.05) and increased amount of elastic fibers in the carotid wall of SHR and SHR-sp. CONCLUSION β carotene supraphysiological supplementation caused no toxic effects, showed positive response in the modulation of blood pressure and lower serum malondialdehyde. No significant morphological changes were observed in the groups studied, except for an increase in the number of elastic fibers in the carotid muscular layer, suggesting elastosis in SHR and SHR-sp.

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.