Antidotal effect of dihydroxyacetone against phosphine poisoning in mice

Phosphine (PH₃ ) is widely used as an insecticide and rodenticide. On the contrary, many cases of PH₃ poisoning have been reported worldwide. Unfortunately, there is no specific antidote against PH₃ toxicity. Disruption of mitochondrial function and energy metabolism is a well-known mechanism of PH₃ cytotoxicity. Dihydroxyacetone (DHA) is an adenosine triphosphate supplying agent which significantly improves mitochondrial function. The current study was designed to evaluate DHA's effect on inhalational PH₃ poisoning in an animal model. DHA was injected into BALB/c mice before and/or after the start of the PH₃ inhalation. The cytochrome c oxidase activity was assessed in the animals' brain, heart, and liver exposed to PH₃ (for 15, 30, and 60 min, with and without the antidote). The LC₅₀ of PH₃ was calculated to be 18.02 (15.42-20.55) ppm over 2 h of exposure. Pretreatment of DHA (1 or 2 g/kg) increased the LC₅₀ of PH₃ by about 1.6- or 3-fold, respectively. Posttreatment with DHA (2 g/kg) increased the LC₅₀ of PH₃ by about 1.4-fold. PH₃ inhibited the activity of cytochrome c oxidase in the assessed organs. It was found that DHA treatment restored mitochondrial cytochrome c oxidase activity. These findings suggested that DHA could be an effective antidote for PH₃ poisoning.