Paraquat, Between Apoptosis and Autophagy

Paraquat (PQ, methyl viologen), 1,1'-dimethyl-4,4'-bipyridinium (Figure 1), is a commonly used, potent herbicide. It was first synthesised in 1882 by Weidel and Russo, as recorded by Hadley in his review of 1979 (Haley, 1979), and its redox properties were discovered by Michaelis and Hill in 1933 (Haley, 1979). Initially, PQ was used as an indicator of oxidationreduction because in the absence of molecular oxygen, donating an electron to paraquat (PQ2+) generated a monocationically stable violet or blue form that is commonly known as methyl viologen (Dinis-Oliveira et al., 2008). However, its properties as an herbicide were not discovered until 1955, and in 1962, it was introduced into global markets. The PQ is registered and used in approximately 100 countries worldwide and is the second most commonly used herbicide in the world after gliphosate. Despite this, its use is currently banned in the European Union (EU), but the import of products from outside the EU for patients who have been treated with PQ has not. In its recommended rating of "pesticides by risk," WHO (World Health Organization) considers composite PQ to be moderately toxic (Category II) (World Health Organization 2004). The ECB (European Chemicals Bureau) classifies PQ as being very toxic (R26) by inhalation, toxic (R25) orally and moderately toxic (R24) dermally. PQ is included in the family of herbicides called bipyridines. It is an herbicide that is nonselective and functions systemically through contact without acting on the leaves of green plants. Among its advantages, it is rapidly absorbed by the leaves of plants that have been sprayed, but clay soil causes it to be biologically inactive. Its action on plants has been shown to occur on chloroplasts and is based on its redox cycle. PQ interferes with photosynthesis at the level of photosystem I. At this point, PQ blocks the flow of electrons from ferredoxin and NADP+ so that electrons from photosystem I would reduce PQ, which transfers divalent cations (normal state) to monovalent cations (reduced state). The monovalent cation reduces oxygen to the superoxide radical (O2-), which is produced by the loss of activity of the chloroplasts and the subsequent cell damage that leads to plant death. There is controversy about the use of PQ in agriculture because herbicides are toxic to humans and the environment, especially when not taking the proper precautions. Specifically, in addition to the adverse effects on humans, one of the greatest