Anthrahydroquinone-2-6-disulfonate is a novel, powerful antidote for paraquat poisoning.

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AHQDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AHQDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AHQDS group significantly decreased compared to the PQ only group. Additionally, AHQDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AHQDS group and the PQ group by NextGen sequencing, and we verified that Nrf2's expression in the PQ + AHQDS group was significantly higher than that in the PQ group. Our work identified that AHQDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.