Resveratrol protects against oxidative stress by activating the Keap‑1/Nrf2 antioxidant defense system in obese‑asthmatic rats

Abstract

The aim of the present study was to investigate the potential mechanism underlying the anti-obesity-asthmatic effects of resveratrol (RSV) in a rat model of obese-asthma. Rat models of obesity and asthma were established using a high-fat diet and the administration of ovalbumin, respectively. Rats were divided into 7 different groups: A normal control, a normal obese, a normal asthma, a normal obese + asthma, a RSV obese, a RSV asthma and a RSV obese + asthma group. Body weight, Lee index, body fat and lung histopathological changes were evaluated. Serum lipid levels were evaluated using calorimetric methods. Levels of reactive oxygen species (ROS) were examined using enzyme-linked immunosorbent assays. Cellular antioxidant enzyme activities were measured using commercial kits. Levels of kelch-like ECH associated protein 1 (Keap-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) was examined using western blot analysis. The results indicated that obese and asthma rat models were successfully established. It was also demonstrated that RSV decreased fasting blood glucose in obese, asthmatic and obese-asthmatic rats. RSV altered serum lipid levels; it significantly increased high density lipoprotein cholesterol levels and significantly decreased serum triglyceride, serum total cholesterol and very low density lipoprotein levels, compared with untreated obese, asthmatic and obese-asthmatic rats (P<0.05). ROS levels were significantly decreased in the RSV treatment group compared with obese, asthmatic and obese-asthmatic rats (P<0.05). RSV treatment significantly increased catalase, glutathione, glutathione peroxidase and total superoxide dismutase levels compared with untreated obese, asthmatic and obese-asthmatic rats (P<0.05). Furthermore, RSV treatment significantly downregulated Keap-1 and upregulated Nrf2 levels in the heart, lung and kidney tissues of rats compared with untreated controls. Therefore, the results demonstrate that RSV protects against oxidative stress by activating the Keap-1/Nrf2 antioxidant defense system in obese-asthmatic rat models.

Role of Resveratrol in Regulating Cutaneous Functions

“…Treatment of keratinocytes with resveratrol either before or post-UVA irradiation lowers expression levels of Keap1 protein [86]. Resveratrol-induced reduction of Keap1 expression was also observed in the kidney and lung tissues of obese and asthmatic rats [185]. Reductions in Keap1 expression can slow Nrf2 degradation, resulting in an increase in Nrf2 expression.…”

“…Moreover, upregulation and activation of Nrf2 expression by SIRT1 were also observed [183]. e second mechanism comprises direct upregulation of Nrf2 expression because studies have shown that resveratrol increases Nrf2 expression in kidney, heart, and lung tissues [184,185]. e third mechanism is direct downregulation of Keap1 expression.…”

Highlighting Curcumin-Induced Crosstalk between Autophagy and Apoptosis as Supported by Its Specific Subcellular Localization

“…On the other hand, the anti-inflammatory action of curcumin [56][57][58] has two aspects: the first is mediated through its ability to inhibit cyclooxygenase-2 (COX-2), lipoxygenase (LOX), and inducible nitric oxide synthase (iNOS) [59,60], and the second is mediated through the ability of curcumin to activate directly antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) [48]. Low-and medium-concentration curcumin decreased malondialdehyde (MDA) and ROS levels and nfr2 KEAP-1 induction [58].…”

Dimethyl Fumarate and Its Esters: A Drug with Broad Clinical Utility?

“…The Nrf2 pathway is considered a critical cellular defence system that responds to potentially toxic stimuli via the upregulation of antioxidant and Phase II cytoprotective response genes [ 19 , 20 ]. A number of Nrf2 inducing drugs have been developed and tested in clinical [ 1 , 21 , 22 , 23 , 24 ] and pre-clinical [ 25 , 26 , 27 , 28 , 29 ] studies over the past decade and many have demonstrated potential for clinical progression. These studies highlight the broad therapeutic utility of targeted Nrf2 activation against a variety of diseases (summarised in Table 1 ).…”