The possible link between aluminum phosphide poisoning and NLRP3 inflammasome

Abstract

Aluminum phosphide (AlP) is a fumigant used to control pests. However, human exposure to this substance can lead to poisoning. AlP reacts with gastric acid and water to release phosphine (PH3). This toxic gas affects the mitochondria and quickly enters the bloodstream. This gas impairs the mitochondria's ability to generate ATP, leading to oxidative stress, mitochondrial dysfunction, and damage to mitochondrial DNA (mt-DNA). Mitochondria release damage-associated molecular patterns (DAMPs) to shield cells from stress and stimulate the innate immune system.Nonetheless, if mitochondrial homeostasis is disrupted, an excessive immune response can occur, causing organ dysfunction. Mitochondrial reactive oxygen species (mt-ROS) and mt-DNA act as DAMPs. Upon recognition of DAMPs, the inflammasome is activated, causing inflammation. The nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) gene on chromosome 1's extended arm encodes a protein that triggers the human inflammasome. NLRP3 is the most extensively researched inflammasome subfamily. It is essential to recognize that the pathophysiology of mitochondrial dysfunction and NLRP3 activation is complex and multifactorial, and a comprehensive approach may be needed to address both the underlying causes and downstream inflammatory responses effectively. The cGAS-STING pathway is essential for immune responses, and targeting specific nodes can be beneficial. Therapeutic approaches include small molecule drugs, biologics, vaccines, and combination therapies. Since there is a significant relationship between mitochondrial events and NLRP3 activation, targeting this inflammasome could be a promising strategy for developing antidotes for AlP poisoning.