Background
Heat stroke (HS) can lead to the development of pulmonary ferroptosis. The inhibition of pulmonary ferroptosis during HS improves patient prognosis. The
Conclusions
RES effectively protected HS rats from lung injury, inhibited the accumulation of Fe2+, ROS, and MDA in the lung, and upregulated FTH1, GPX4, SLC7A11, Nrf2, NQO1, and HO-1.
Methods
Heat stress was induced in Beas-2B cells and lung injury was induced in HS rats at an ambient temperature of 42 °C. The anti-oxidative stress and anti-ferroptotic effects of RES were confirmed through tail vein injection of nuclear factor-2 associated factor (Nrf2) shRNA recombinant adeno-associated virus 6 (AAV6-shNrf2).
Results
RES treatment attenuated the upregulation of reactive oxygen species (ROS) and malondialdehyde (MDA) levels and alleviated glutathione inhibition in HS. In addition, RES treatment reduced the accumulation of Fe2+ in heat-stressed Beas-2B cells and increased the ferroptosis resistance-related proteins FTH1, GPX4, and SLC7A11 as well as the anti-oxidative stress pathway proteins Nrf2, NQO1, and HO-1. The antioxidant and anti-ferroptotic effects of RES in heat-stressed Beas-2B cells were effectively reversed upon treatment with Nrf2-IN-1, an Nrf2 pathway inhibitor. In the HS rat model, the antioxidant and anti-ferroptotic effects of RES were reversed by an ambient temperature of 42 °C and relative humidity of 60 ± 5%. Conclusions: RES effectively protected HS rats from lung injury, inhibited the accumulation of Fe2+, ROS, and MDA in the lung, and upregulated FTH1, GPX4, SLC7A11, Nrf2, NQO1, and HO-1.