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Background and Aim: Individuals exposed to heavy metals are known to experience physiological and biochemical changes, which raise questions regarding possible health effects. In our earlier research, significant concentrations of vanadium (V), mercury (Hg), cadmium (Cd), and arsenic (As) were found in food and medical packaging materials. This study aimed to evaluate the cognitive, physiological, and biomarker effects of select heavy metal exposure in Wistar rats. Materials and Methods: Over a 13-week period, five groups of rats (six rats per group, with both males and females) were assessed to study the effects of oral exposure to V, Hg, Cd, and As. The study focused on evaluating physiological, cognitive, and biochemical markers, with the results compared to those of a control group. Results: Comparing all groups of rats treated with heavy metals, the study revealed significant deficits in learning and spatial orientation (water maze test); rats treated with V, Cd, and Hg showed signs of depression. Rats treated with As also showed signs of hyperactivity, which may indicate a connection to attention-deficit hyperactivity disorder (rat tail suspension test). The groups exposed to different heavy metals varied in their physiological (water and food intake, urine and feces output) and biochemical responses (enzyme-linked immunosorbent assay, prostate-specific antigen, T3, T4, thyroid-stimulating hormone, carcinoembryonic antigen, and blood glucose analysis), with Hg exhibiting the strongest impacts. Rats given Hg showed signs of hypothyroidism, such as increased food intake and weight gain. Conclusion: This study clarifies the complex relationships between exposure to heavy metals and various biological systems, shedding light on their potential health impacts. The findings provide insight into the effects of heavy metals on neural and thyroid tissues, as well as their propensity to cause cellular dedifferentiation. However, the study has certain limitations, such as the relatively short duration of exposure and the use of only a few selected biomarkers. Future research should focus on long-term exposure studies, incorporate a broader range of biomarkers, and explore the underlying mechanisms at a molecular level to better understand the full spectrum of health risks associated with heavy metal exposure.
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The goal of this research was to study the effect of different doses of resveratrol (RS) and RS with donepezil (DPZ) on the deposition of amyloid beta (Aß) and neurofibrillary tangles (NFTs) in colchicine-induced Alzheimer's disease (AD) brain. The study included three months old male Albino Wistar rats and consisted of six animal groups: AD model (group 1), treatment groups, RS 10 mg/kg body weight (group 2), RS 20 mg/kg body weight (group 3), RS 10 mg/kg body weight along with DPZ 1 mg/kg body weight (group 6), prophylaxis groups, RS 10 mg/kg body weight (group 4) and RS 20 mg/kg body weight (group 5). In the treatment groups, RS was given for 7 consecutive days from the day of induction of AD, and in the prophylaxis groups, we started RS 7 days even before the induction of AD and continued for seven days after the induction. The number of Aßs and NFTs at the frontal region, cornu ammonis (CA) 1,2,3,4 and dentate gyrus regions of hippocampus were evaluated. The immunohistochemical analysis was performed by using mouse anti-ß-amyloid antibody for the Aß plaques and polyclonal rabbit anti-human tau for the tau-positive neurons. The present study observed the accumulation of Aß plaques and tau-positive neurons in the AD model. However, their numbers were significantly decreased in the treatment groups (p < 0.001). The best results were observed when RS 10 mg was given prophylactically (p < 0.01) and RS along with DPZ (p < 0.001), suggesting the neuroprotective effect of RS and its synergistic effect with the DPZ.
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Aim: The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and astrocytes, in the frontal cortex, regions of the hippocampus in colchicine-induced Alzheimer's disease (AD) model. Methods: The study involved male albino Wistar rats of three months, age and consisted of 6 groups, with six animals each. The immunohistochemical staining with mouse monoclonal anti-human CD 68 and mouse monoclonal anti-GFAP was performed to assess the number of microglial cells and astrocytes, respectively. Results: AD group showed an increase in the number of microglia, and the numbers declined in the treatment groups, RS 10, RS 20, RS10/10 and DPZ + RS (p < 0.001). Astrocyte count was increased in the treatment groups in contrast to the AD group (p < 0.05). The DPZ + RS combination group revealed substantial elevation in the number of astrocytes and decreased microglial number among all the groups (p < 0.001). Conclusion: RS administration has diminished the microglial number and elevated the number of astrocytes. The elevated reactive astrocytes have decreased the microglial population. However, the limitation of our study is utilizing the colchicine for the induction of neurodegeneration. Using the transgenic models of AD may give a better insight into the pathogenesis and effect of RS. Another limitation of this study is the administration of RS and DPZ through different routes. The prospects of this research include studying the probiotic nature of RS and the effect of RS in other neurodegenerative disorders.
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Hippocampus is the significant component of the limbic lobe, which is further subdivided into the dentate gyrus and parts of Cornu Ammonis. It is the crucial region for learning and memory; its sub-regions aid in the generation of episodic memory. However, the hippocampus is one of the brain areas affected by Alzheimer's (AD). In the early stages of AD, the hippocampus shows rapid loss of its tissue, which is associated with the functional disconnection with other parts of the brain. In the progression of AD, atrophy of medial temporal and hippocampal regions are the structural markers in magnetic resonance imaging (MRI). Lack of sirtuin (SIRT) expression in the hippocampal neurons will impair cognitive function, including recent memory and spatial learning. Proliferation, differentiation, and migrations are the steps involved in adult neurogenesis. The microglia in the hippocampal region are more immunologically active than the other regions of the brain. Intrinsic factors like hormones, glia, and vascular nourishment are instrumental in the neural stem cell (NSC) functions by maintaining the brain's microenvironment. Along with the intrinsic factors, many extrinsic factors like dietary intake and physical activity may also influence the NSCs. Hence, pro-neurogenic lifestyle could delay neurodegeneration.
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The aim of this study was to determine the malondialdehyde (MDA) level and superoxide dismutase (SOD) activity in colchicine induced Alzheimer's disease (AD), resveratrol (RS) treated and RS + donepezil (DPZ) treated rat models. The objective was to compare the MDA level and SOD activity among these rat models. The present study included 3 months old male albino Wistar rats, which were in-house bred and weighting about 220-250 g. The rats were divided into nine subgroups which included control, sham, AD induced, RS treated and DPZ treated groups in different doses and combinations. The lipid peroxidation product for MDA in the brain homogenate was measured by estimating the levels of thiobarbituric acid reactive substance. Estimation of SOD was done by the method of autoxidation of pyrogallol by Marklund and Marklund. There was a marked increase in the MDA levels in AD induced group in comparison to the control group (p < 0.05). The SOD activity was higher in the RS 10 and RS 20 treated groups in contrast to the AD group (p < 0.05). In DPZ + RS group, there was a substantial increase in the SOD activity (p < 0.05). It is also observed that the RS 20 treatment group showed higher SOD activity than the RS 10 group (p < 0.05). This study showed that, AD induced group had elevated levels of MDA, which indicates the poor oxidative stress-defence mechanism. The RS 10 and RS 20 groups showed higher SOD activity in comparison to the AD group, which indicated the improved oxidative stress-defence mechanism. The RS + DPZ group showed higher SOD activity, indicating a synergistic effect of DPZ and RS.