Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol

Abstract

Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis.

Modulation of autophagy in the protective effect of resveratrol on PM2.5‐induced pulmonary oxidative injury in mice

“…Previous studies showed that resveratrol activates autophagic cell death in several cancer cell lines (Selvaraj, Sun, Sukumaran, & Singh, ). However, it has also been found that resveratrol inhibits reactive oxygen species and autophagy in adjuvant‐arthritis rats (Zhang et al, ). Resveratrol suppresses hydrogen peroxide‐induced autophagy and apoptosis in cardiomyocyte cells (Huang, Ting, Huang, Yang, & Lin, ).…”

“…Resveratrol‐induced autophagy has been suggested to exert beneficial effects of resveratrol (Park et al, ). However, recent studies demonstrate that resveratrol‐mediated inhibition of autophagy can antagonize oxidative injuries (Huang, Ting, Huang, Yang, & Lin, ; Zhang et al, ). In addition, resveratrol protects lung cells form PM‐induced cytotoxicity (Fahmy et al, ; Salcido‐Neyoy et al, ).…”

Inhibition of DNM1L and mitochondrial fission attenuates inflammatory response in fibroblast‐like synoviocytes of rheumatoid arthritis

“…6 A previous study has shown that excessive ROS induces mitophagy, 7 and feedback can remove damaged mitochondria to reduce ROS accumulation. 9 It is notable that a defect in the mitochondrial respiratory chain (MRC) complex IV, and increased autophagy (mediated by LC3 and Beclin 1) are associated with the development of RA. 9 It is notable that a defect in the mitochondrial respiratory chain (MRC) complex IV, and increased autophagy (mediated by LC3 and Beclin 1) are associated with the development of RA.…”

Resveratrol Role in Autoimmune Disease—A Mini-Review

“…Besides the anti-inflammatory effect, resveratrol is considered a potential agent for RA therapy, because it is an excellent scavenger of hydroxyl, superoxide, and other radicals and improves antioxidant defenses, such superoxide dismutase (SOD), catalase, thioredoxin, and GSH-Px [ 88 , 89 , 90 ]. Zhang et al (2016) showed reducing oxidative injury parameters in adjuvant arthritis rats that were treated for 12 days with resveratrol (5, 15, 45 mg/kg) led to a significant reduction in MDA content capacity, glutathione peroxidase, and the glutathione reductase ratio [ 90 ]. Wahba, Messiha, and Abo-Saif (2016) also reported that treatment with 10 mg/kg/day of resveratrol in rats with arthritis, induced by complete Freund’s adjuvant (CFA), restored serum MDA and glutathione (GSH) levels back to normal.…”