Piezo1-mediated iron overload in the oxidative damage to the liver in hypobaric hypoxia and the alleviation by selenium synthesized by Lactobacillus rhamnosus SHA113

Oxidative damage is harmful to human health, which becomes serious in high-altitude areas due to the low oxygen partial pressure there. However, which organs are mostly influenced and the mechanisms of these are not clear. This study found that the liver was more susceptible to oxidative damage than other organs after mice entered a hypobaric hypoxia condition (4000 m). Only after 6 h of hypobaric hypoxia exposure, obvious oxidative damage was observed in hepatic tissues. The key role of Piezo1 mediated iron overload in the cause of such damage by using Piezo1 inhibitors and activators. Piezo1-mediated iron influx and the inhibition of iron efflux by hepcidin activation contributed to this process. Selenium accumulation in the liver coincided with this iron overload, suggesting a stress response. Oral administration of Lactobacillus rhamnosus SHA113-synthesized biological selenium significantly enhanced the selenium content, inhibited Piezo1 mediated iron overload and protected against oxidative damage to the liver under hypobaric hypoxia. These findings underscore that Piezo1-mediated iron overload was a key contributor to the oxidative damage to the liver in high-altitude environment; selenium accumulation was a stress response to this damage; oral supplementation of biological selenium in advance might be an efficient way to protect the liver and human health in hypobaric hypoxia.