Resveratrol decreases fructose‐induced oxidative stress, mediated by NADPH oxidase via an AMPK‐dependent mechanism

Abstract

BACKGROUND AND PURPOSEOxidative stress is an important pathogenic factor in the development of hypertension. Resveratrol, the main antioxidant in red wine, improves NO bioavailability and prevents cardiovascular disease. The aim of this study was to examine whether resveratrol decreases the generation of reactive oxygen species (ROS), thereby reducing BP in rats with fructose-induced hypertension. EXPERIMENTAL APPROACHRats were fed 10% fructose with or without resveratrol (10 mg·kg ) for 1 week or for 4 weeks with resveratrol treatment beginning at week 2; systolic BP (SBP) was measured by tail-cuff method. Endogenous in vivo O2− production in the nucleus tractus solitarii (NTS) was determined with dihydroethidium. Real-time PCR and immunoblotting analyses were used to quantify RNA and protein expression levels. KEY RESULTSIn fructose-fed rats, ROS levels in the NTS were higher, whereas the NO level was significantly decreased. Also, RNA and protein levels of NADPH oxidase subunits (p67, p22-phox) were elevated, superoxide dismutase 2 (SOD2) reduced and AMP-activated PK (AMPK) T172 phosphorylation levels in the NTS were lower in fructose-fed rats. Treatment with the AMPK activator resveratrol decreased levels of NADPH oxidase subunits and ROS, and increased NO and SOD2 levels in the NTS of fructose-fed rats. Administration of resveratrol, in combination with fructose at week 0 and later at week 2, significantly reduced the SBP of fructose-fed rats. CONCLUSIONS AND IMPLICATIONSCollectively, resveratrol decreased BP through the phosphorylation of AMPK, Akt and neuronal NOS in fructose-fed rats. These novel findings suggest that resveratrol may be a potential pharmacological candidate for the treatment of hypertension. Abbreviations

Resveratrol attenuates high glucose-induced oxidative stress and cardiomyocyte apoptosis through AMPK

“…In our experimental system, we have shown that AMPK activation is involved in the protective effects of resveratrol on cardiomyocytes through suppressing high glucose-induced oxidative stress. Our results was similar with previous in vivo study that resveratrol decreases fructose-induced oxidative stress mediated by NADPH oxidase via an AMPK-dependent mechanism (Cheng et al, 2014). Balteau et al suggested that NADPH oxidase activation by hyperglycemia in cardiomyocytes is independent of glucose metabolism (Balteau et al, 2011).…”

The Murphy Roths Large (MRL) mouse strain is naturally resistant to high fat diet-induced hyperglycemia

“…pAMPK is also know to inhibit TGFβ1 signaling, which would further reduce pathologic inflammation and fibrosis [29]. Lastly, pAMPK also inhibits reactive oxygen species [30], reducing the pathologic consequences of an over active immune response even further. Therefore, the naturally increased pAMPK found in the MRL skeletal muscle tissue can inhibit HFD pathologies at multiple points.…”

Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases

“…For instance, resveratrol microinjection into the rostral ventrolateral medulla lowered BP and heart rate by decreasing the sympathetic vasomotor tone [66], which may be mediated through NO synthesis and a decrease in Ca 2+ influx [66]. Resveratrol has also been shown to activate AMPK in the nucleus tractus solitarii (NTS) in the brainstem of fructose-fed rats [67], and it has been proposed that this activation lowers BP through decreasing ROS generation, enhancing Akt-nNOS pathway activity, and up-regulating SOD2 levels in the NTS [67].…”