By Nikhil Saxena and Divya Bajpai
Paraquat (1,1′-dimethyl-4,4′-bipyridinium dichloride) is a highly potent nonselective contact herbicide that is inexpensive and widely used in Southeast Asia, the Americas, and the Pacific (1). Although short-term dermal contact is relatively safe, ingestion has a very high fatality case rate (up to 60%–80%) (2), with a lethal dose as low as 30 mg/kg (10–20 mL of 20% solution) (1, 2). Intoxication—either accidental or deliberate—primarily happens via ingestion or inhalation, and it is a significant health concern, especially in agricultural communities.
Following ingestion, the stomach absorbs 20% of the poison, which is rapidly distributed to tissues with high blood flow and energy requirements (lungs, kidneys, liver, and muscles). Peak tissue concentrations are reached in 6 hours. Intracellularly, paraquat is oxidized in the presence of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) cytochrome P450 reductase and nitric oxide synthase, generating superoxide, peroxynitrite, and hydroxyl radicals (3). These free radicals lead to increased expression of nuclear factor-κB and activation of nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin (NLRP) inflammasome, ultimately leading to the generation of cytokines, including interleukin-1β, interleukin-18, and tumor necrosis factor α. Paraquat also induces the intracellular activity of death-associated protein kinase, which is required to assemble the NLRP protein 3 (NLRP3) inflammasome. Ultimately, NADPH depletion and free radical generation cause mitochondrial and cell membrane damage, nuclear condensation, and DNA fragmentation, culminating in apoptosis.
https://www.kidneynews.org/view/journals/kidney-news/16/8/article-p17_9.xml
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