Repurposing of sevelamer as a novel antidote against aluminum phosphide poisoning: An in vivo evaluation

Abstract

Aluminum phosphide (AlP) is widely used for protecting grains from pests. AlP releases toxic phosphine gas (PH3) while exposed to humidity. Poisoning with these tablets is dangerous and can cause death or serious injuries. Up to now, no definite antidote has been introduced for specific treatment of this poisoning. Sevelamer carbonate or sevelamer hydrochloride (Renagel) is a polymeric pharmaceutical prescribed for treating hyperphosphatemia in patients with chronic kidney disease. Sevelamer can bind with phosphate groups and act as an anion exchanger. Herein, sevelamer is repurposed as a potent antidote agent in phosphine gas poisoning. In vivo evaluation was conducted on male Sprague Dawley rats. The evaluation was conducted on three groups of animals: control, AlP-poisoned, and AlP-poisoned treated with sevelamer. Survival percentage, serum biomarkers level of organ injury, and ATP level were recorded. The results indicate a high survival rate in sevelamer-treated animals compared with the AlP-poisoned group (75% vs. 0% respectively, 48 h after poisoning). The analysis of serum markers of organ injury also showed that sevelamer could reduce toxicity and organ injury in poisoned animals. ATP level of separate organs showed that sevelamer treated groups were recovered. The results showed that sevelamer could be a potent antidote for managing aluminum phosphide poisoning. Moreover, a mechanism is suggested for the interaction of sevelamer with phosphine gas.