Aspartate deficiency amplifies cGAS-STING signaling in antitumor immunity.

INTRODUCTION AND

OBJECTIVE

The antioxidant N-acetylcysteine (NAC) may help in the treatment of organophosphates poisoning, including Pirymiphos methyl (PM). However, there is no information on the effect of NAC on target cholinesterases during the core treatment with atropine and obidoxime after acute and chronic exposure to PM. The impact was investigated of NAC on the functional status of target cholinesterases in the brain and blood during treatment with atropine (ATR) and/or obidoxime (OBID) in PM-induced toxicity.

MATERIAL AND

METHODS

All experiments were performed on Male Swiss mice. The animals were intoxicated with PM and treated with OBID and/or ATR with or without and NAC, in various combinations (with 2-3 drugs) used simultaneously after intoxication. Total acetylcholinesterase activity (AChE) in brain and blood and plasma butyrylcholinesterase activity (BChE) were monitored at 2 and 72 h after intoxication. Enzyme activity was determined using Ellman's colorimetric method.

RESULTS

The applied therapies with OBID, ATR and NAC in various configurations significantly reactivated PM-inhibited AChE in the brain and erythrocytes and the BChE in the plasma. The benefits of NAC administration in combination with ATR and/or OBID therapy have also been reported to restore AChE activity in the brain. NAC may reduce the dose of ATR in the treatment of PM poisoning.

CONCLUSIONS

Adjunctive treatment offered by NAC can reduce or prevent the deleterious effects against PM-induced toxicity. Therefore, NAC remains a strong candidate for adjunct treatment for OP-poisoning, including PM, although additional preclinical and clinical studies are needed.