Paraquat: An Oxidative Stress Inducer

Book Chapter

Summary *

Paraquat (1,1_-dimethyl-4,4_-bipyridinium dichloride), is a foliar-applied and non selective bipyridinium herbicides, and it is one of the most widely used herbicides in the world, controlling weeds in a huge variety of crops like corn, rice, soybean, wheat, potatoes; major fruits: apples, oranges, bananas; beverages: coffee, tea, cocoa; and processed crops: cotton, oil palm, sugarcane and rubber. For a foliar absorbed herbicide to completely kill a plant, it must be capable of accessing the whole plant, as growing leaves and newly emerging roots. This often means that the herbicide not only needs to damage at the point of its absorption, but must also be translocated to parts of the plant not contacted by the herbicide during application. Paraquat is a cation formed by two pyridine rings, each having a quaternary amine and thus charged 2+. Although the majority of herbicides are passively transported as noionic molecules, paraquat cation movement by diffusion across membrane lipid bilayer is unlikely. Transporter studies to explain paraquat compartment were made using several systems. ABC transporters, large membrane proteins which use ATP for the active transport of several compounds including paraquat have been described. Other groups of transporters are small antiporter proteins which exchange protons for some other molecules using the proton electrochemical potential gradient (Morymio et al., 1992, Yerushalmi, et al., 1995).  In animal tissues it has been shown that paraquat transport occurs by carriers that also function as carriers of other molecules such as polyamines (Rannels et al., 1989, Jóri et al., 2007). Hart et al. (1992a 1992b) demonstrated that paraquat movement across plasma membrane root epidermal and cortical maize cells has a concentration-dependent kinetic and that the herbicide binds to cell wall, and its transport is facilitated by a carrier that normally functions in the movement of molecules that has a similar chemical structure or similar charge distribution such us diamines like putrescine and cadaverine. Using maize protoplast Hart et al. (1993) showed that paraquat uptake has similar concentration-kinetic to that observed in intact cells and the accumulation inside cells increase in a time-dependent manner and is saturated after 10 min,  although 50% of uptake occurs during the first 10 s. The saturable Km for paraquat uptake in maize cells and protoplasts was determined at 90 µM and 132 µM respectively, similarly the Km in rat lung was 70 µM suggesting in both animal and vegetal tissues a carrier-mediated process (Rannels et al., 1985). In order to investigate paraquat uptake, compartmentation and translocation, maize plantlets with their root immersed in paraquat solution for several loading periods were used (Hart et al., 1993). The lack of chloroplasts in roots provides a system to minimize the short-term phototoxic effect. The paraquat accumulation in the root vacuole was linear over a 24 h loading period. The vacuolar paraquat content, with respect to the total accumulated increased from 15% to 42% after 2 h and 24 h loading period, respectively. In contrast to the vacuole, total cytoplasmic paraquat content appeared to approach saturation whereas paraquat associated with the cell wall fraction remained relatively constant, suggesting that this phase is rapidly saturated. Even though paraquat is considered to be relatively immobile, linear PQ translocation occurred from roots to shoots and was estimated that approximately 50% of the paraquat effluxing from roots started translocation to shoots 5 h after the beginning of loading period (Hart et al., 1993b). Paraquat is a cation formed by two pyridine rings, each having a quaternary amine and thus charged 2+, which acts as a redox cycler with a great negative reduction potential (E0 = – 0.446 V). This feature that restricts its interaction with strong reductant compounds. When dication of paraquat (PQ 2+) accepts an electron from a reductant form the paraquat monocation radical (PQ.+), which then rapidly reacts with  oxygen (O2  Eo =  0.16 V) to initially produce  superoxide radical (O2•−) (k 7.7 x 108 M-1 s -1) and subsequently the other reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) and hydroxyl radical (.OH) In plants, paraquat is principally reduced within chloroplasts, where it acts as an alternative electron acceptor taking electron from Fe-S proteins of photosystem I; inhibiting the ferredoxin reduction, the NADPH generation, and also the regeneration of ascorbic acid. In consequence, paraquat is a potent oxidative stress inducer, because it greatly increases the ROS production and inhibits the regeneration of reducing equivalents and compounds necessary for the activity of the antioxidant system. Paraquat also induces the increase of superoxide radical production in mitochondria, where complexes I and III are the major electron donors.  For this reason paraquat has been widely used to induce mitochondrial oxidative stress in many experimental systems such as isolated mitochondria, cultured cells, and whole organisms including plants, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster  and rodents (Cocheme & Murphy, 2008)  Information provided by the agent in SIGEVA