Role of Resveratrol and Selenium on Oxidative Stress and Expression of Antioxidant and Anti-Aging Genes in Immortalized Lymphocytes from Alzheimer’s Disease Patients

Abstract

Oxidative damage is involved in the pathophysiology of age-related ailments, including Alzheimer’s disease (AD). Studies have shown that the brain tissue and also lymphocytes from AD patients present increased oxidative stress compared to healthy controls (HCs). Here, we use lymphoblastoid cell lines (LCLs) from AD patients and HCs to investigate the role of resveratrol (RV) and selenium (Se) in the reduction of reactive oxygen species (ROS) generated after an oxidative injury. We also studied whether these compounds elicited expression changes in genes involved in the antioxidant cell response and other aging-related mechanisms. AD LCLs showed higher ROS levels than those from HCs in response to H2O2 and FeSO4 oxidative insults. RV triggered a protective response against ROS under control and oxidizing conditions, whereas Se exerted antioxidant effects only in AD LCLs under oxidizing conditions. RV increased the expression of genes encoding known antioxidants (catalase, copper chaperone for superoxide dismutase 1, glutathione S-transferase zeta 1) and anti-aging factors (sirtuin 1 and sirtuin 3) in both AD and HC LCLs. Our findings support RV as a candidate for inducing resilience and protection against AD, and reinforce the value of LCLs as a feasible peripheral cell model for understanding the protective mechanisms of nutraceuticals against oxidative stress in aging and AD.

Resveratrol decreases cell apoptosis through inhibiting DNA damage in bronchial epithelial cells

“…In the present study, high expression levels of 8-OHdG/8-oxoG were detected, which indicated that the bronchial epithelial cells were damaged. In vitro studies have shown that RES induces the production of antioxidants to reduce the impact of ROS (43)(44)(45). A study on RES indicated that treatment of aged rats with RES can activate Nrf2 and attenuate oxidative stress in endothelial cells.…”

Anti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept

“…Previous studies have indicated the beneficial effects of sirtuins as the best small molecule that activate sirtuins, which extended lifespan in a yeast model [104][105][106][107][108][109]. Although only the longevity extension effect of resveratrol has been reported in C. elegans and D. melanogaster, many subsequent studies reported that resveratrol intake promotes health and plays a preventive role in age-related diseases, such as cancer [110][111][112][113], atherosclerosis [114,115], arthritis [116,117], cataract [118][119][120], cardiovascular disease [121], hypertension [122,123], type 2 diabetes [124][125][126][127], osteoporosis [128][129][130], and Alzheimer disease [131][132][133]. In clinical studies, resveratrol intake improved the memory capacity of elderly individuals and reduced blood lipid levels in obese and type 2 diabetic patients [134,135].…”

A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases

“…This was shown by Mokni et al [ 168 ], where intraperitoneal resveratrol injection of 12.5 mg/kg BW/day for seven days in healthy Wistar rats increased the activity of antioxidant enzyme SOD (2.60 ± 0.09 U/mg), CAT (1.32 ± 0.12 nmol/min/mg), and peroxidase (19.20 ± 3.00 nmol/min/mg) in the brain compared to control (1.60 ± 0.14 U/mg, 0.48 ± 0.03 nmol/min/mg, and 9.00 ± 3.60 nmol/min/mg; respectively, p < 0.05) ( Table 3 ). The result was corroborated by another study in lymphoblastoid cell lines of AD patients, whereby 50 µM of resveratrol treatment significantly upregulated the gene expression of the antioxidant system including CAT , SOD2 , and NFE2L2 compared to AD control (relative mRNA expression: 3 vs. 1, 2.5 vs. 1, and 2.5 vs. 1, respectively) [ 169 ]. Among all of these, the upregulation of NFE2L2 by resveratrol was the most important in activating the antioxidation system as it encoded the Nrf2.…”