Edaravone promotes viability of random skin flaps via activating PI3K/Akt/mTOR signalling pathway‐mediated enhancement of autophagy

Abstract

Random skin flap transplantation is a commonly used technique. However, ischemia and ischemia–reperfusion injury always impair its therapeutic effectiveness through acclerating oxidative stress, apoptosis and suppressing angiogenesis. To survive, cells rely on mediating autophagy, DNA repair, immunoregulation to resist these cellular injuries. Thus, mediating autophagy may affect the survival of random skin flaps. The edaravone (EDA), a oxygen radicals scavenger, also possesses autophagy mediator potential, we investigated the effects of EDA on skin flap survival and its autophagy‐related mechanisms. In vivo, mice were administered EDA or saline intraperitoneally for 7 days postoperatively. We found that EDA ameliorated the viability of random skin flaps, promoted autophagy and angiogenesis, attenuated apoptosis and oxidative stress. In vitro, mouse umbilical vascular endothelial cells (MUVECs) were administered EDA or 3‐methyladenine (3‐MA, an autophagy inhibitor) or rapacymin (Rapa, an autophagy activator) at the beginning of oxygen glucose deprivation (OGD). We found that EDA promoted cell viability, activated autophagy, enhanced angiogenesis, alleviated apoptosis and oxidative stress. On one hand, 3‐MA reversed the effects of EDA on cell viability, oxidative stress and apoptosis via inhibiting autophagy. On the other hand, Rapa had the similar effects of EDA. Furthermore, EDA‐induced autophagy was mediated through downregulating PI3K/Akt/mTOR signalling pathway. The findings showed that EDA ameliorated viability of random skin flaps by promoting angiogenesis, suppressing oxidative stress and apoptosis, which may be mediated by autophagic activation through downregulating PI3K/AKT/mTOR signalling pathway.

Rhapontigenin Improves Non-alcoholic Fatty Liver Disease by Inducing Lipophagy Through the ACOX1 and mTOR/ULK1 Pathways

“…Further, 90 mice were equally divided into nine groups, the treatment was as follows: the control group mice were given a basal diet, the RA group mice were given a basal diet and 8 mg/kg RA daily by gavage, the HFD group mice were given a HFD, the RA + HFD group mice were given at different doses of 2, 4, and 8 mg/kg RA daily by gavage (according to the literature), the positive drug groups were given 5 mg/kg ACT daily (according to the dose of an adult daily) or 60 mg/kg ZBT daily (according to the dose of an adult daily) by gavage, and RA + 3-MA + HFD group was given 8 mg/kg RA daily by gavage, with 30 mg/kg 3-MA (Bi et al, 2023;Chen et al, 2023) dissolved in physiological saline and injected intraperitoneally three times a week. All the other groups were fed a HFD for 8 weeks except the control and RA groups.…”