New insights into antioxidant strategies against paraquat toxicity

Abstract

Paraquat (PQ, 1,1'-dimethyl-4-4'-bipyridinium dichloride) is a highly toxic quaternary ammonium herbicide widely used in agriculture, it exerts its toxic effects mainly because of its redox cycle through the production of superoxide anions in organisms, leading to an imbalance in the redox state of the cell causing oxidative damage and finally cell death. The contribution of mitochondrial dysfunction including increased production of reactive oxygen species besides the reduction in oxygen consumption as well as in the activity of some respiratory complexes has emerged as a key component in the mechanisms through which PQ induces cell death. Although several aspects of PQ-mitochondria interaction remain to be clarified, recent advances have been conducted with reproducible results. Currently, there is no treatment for PQ poisoning; however, several studies taking into account oxidative stress as the main mechanism of PQ-induced toxicity suggest an antioxidant therapy as a viable alternative. In fact, it has been shown that the antioxidants naringin, sylimarin, edaravone, Bathysa cuspidata extracts, alpha-lipoic acid, pirfenidone, lysine acetylsalicylate, selenium, quercetin, C-phycocyanin, bacosides, and vitamin C may be useful in the treatment against PQ toxicity. The main mechanisms involved in the protective effect of these antioxidants include the reduction of oxidative stress and inflammation and the induction of antioxidant defenses. Interestingly, recent findings suggest that the induction of nuclear factor erythroid like-2 (Nrf2), a major regulator of the antioxidant response, by some of the above-mentioned antioxidants, has been involved in the protective effect against PQ-induced toxicity.

Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice

“…The significant attenuation of alveolar collapse and collagen deposition in histological changes after RAPA treatment was comparable to the effects obtained previously with this model using other potential antifibrotic agents such as DHA and naringin (Chen J. et al, 2013;Chen Y. et al, 2013;Blanco-Ayala et al, 2014). Interestingly, the observation period of the test groups in our study (14 and 28 d after RAPA treatment) The blots with anti-TGF-β1 antibody and anti-α-SMA antibody are shown in (a) and (d), respectively, and densitometric analysis normalized against β-actin is shown in (b), (c), (e), and (f) differed from that of other studies of novel antifibrotic agents mentioned above.…”

“…Previous studies have revealed that a combination of glucocorticoid and cyclophosphamide can improve the survival rate of PQ-poisoned patients or animal models, and reduce the pathological changes in the lung tissues, such as inflammatory cell infiltration, in the early stages of acute lung injury (ALI) (Rocco et al, 2003;Li et al, 2014), but this therapy does not have a significant effect in preventing progressive pulmonary fibrosis. Some other potential agents, such as docosahexaenoic acid (DHA) (Chen J. et al, 2013) and naringin (Chen Y. et al, 2013;Blanco-Ayala et al, 2014), have been shown to ameliorate PQ-induced pulmonary fibrosis in animal models. However, these new therapies take a relatively long time to achieve a noticeable antifibrotic effect.…”

Characteristic of the acute drug intoxication conveyed by Kanagawa helicopter emergency medical service

“…Severity at HEMS contact does not appear to be different between the medical agents group and the other agents group, but it seems that if a pesticide is associated as the cause, mortality increases well over the medical agents group. Paraquat, in particular, had a high case fatality rate, and 45.5% of fatal cases reported in two previous studies were caused by paraquat 5, 6. Seven paraquat poisoning cases were transported by the Kanagawa HEMS, and only two of those survived.…”

A rare case of epilepsy and acute pancreatitis induced by severe paraquat poisoning

“…The usage of octreotide acetate and ornidazole sodium chloride in this patient is general usage when the patient appears to be intoxicated with paraquat and the amylase and lipase levels changes. Antioxidants are required to treat oxidative stress in paraquat poisoning (3)(4)(5) and paraquat-induced acute pancreatitis (6). Our patient, who had epilepsy and acute pancreatitis, was cured after receiving timely treatment.…”