ONOO--triggered fluorescence H2S donor for mitigating drug-induced liver injury

Scavenging of toxic active substances (ROS and RNS) and releasing of protective H2S may be a potential strategy to mitigate liver injury caused by clinical drugs. Hence, we designed a fluorogenic ONOO--triggered H2S donor (Z-1). This donor scaffold exhibited a promising turn-on fluorescence signal upon ONOO- activating as a proof of concept. This strategy made Z-1 suitable for not only scavenging harmful ONOO- but also releasing H2S to relief DILI in the cellular and mice model. Additionally, with this proposed sensor, Ferrostatin 1 (ferroptosis inhibitor) was proved to reduce ROS in mitochondria during acetaminophen (APAP)-insulted HepG2 cells and furtherin DILI mice model for the first time, suggesting that preventing ferroptosis might offer a viable therapeutic op-portunity in DILI and other pathologies involving ferroptosis cell death pathways. Overall, Z-1 yielded a potential strategy for mitigating DILI by scavenging of toxic ONOO-, releasing of protective H2S and inhibiting ferroptosis.

Automated summary

We designed a new fluorogenic ONOO--triggered H2S donor (Z-1) for mitigating liver injury caused by toxic active substances. Z-1 can scavenge harmful ONOO- and release H2S to relieve DILI in cellular and mice models. Additionally, we found that the ferroptosis inhibitor Ferrostatin 1 can reduce ROS in mitochondria during acetaminophen (APAP)-induced liver injury, suggesting a potential therapeutic opportunity for preventing ferroptosis in DILI and other related pathologies.