Abstract

Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and widely used herbicide, was commercially introduced in 1962. It is reduced by the electron donor NADPH, and then reduced PQ transfers the electrons to molecular oxygen, resulting in the production of reactive oxygen species (ROS), which are related to cellular toxicity. However, the influence of continuous hypoxia on PQ-induced ROS production has not fully been investigated. We evaluated in vitro the protective effect of continuous hypoxia on PQ-induced cytotoxicity in the human carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live and dead assay, and by measuring lactate dehydrogenase (LDH) release. To elucidate the mechanism underlying this effect, we monitored the immunofluorescence of intracellular ROS and measured malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Continuous hypoxia protected the A549 cells from PQ-induced cytotoxicity. Continuous hypoxia for a period of 24 h significantly reduced intracellular ROS, decreased MDA concentration in the supernatant, and normalized SOD and GPx activities. Continuous hypoxia attenuated PQ-induced cell toxicity in A549 cells. This protective effect might be attributable to the suppression of PQ-induced ROS generation.

Highlights

  • Paraquat (PQ, 1,1'-dimethy-4,4'-bipyridinium dichloride) is a common vegetative herbicide widely used globally since its introduction in the 1960s

  • A number of researches have dem onstrated that the mechanism of PQ cytotoxicity entails interfering with the intracellular electron transfer systems, which generate the formation of superoxide anion, singlet oxygen, and other reactive oxygen species (ROS), leading to the depletion of cellular Nicotinamide adenine dinucleotide phosphate (NADPH) and lipid peroxidation of cell membranes (Smith et al, 1978; Bus and Gibson, 1984; Suntres, 2002; Yeh et al, 2006)

  • Protective effects of continuous hypoxia on the viability of cells subjected to PQ

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Summary

Introduction

Paraquat (PQ, 1,1'-dimethy-4,4'-bipyridinium dichloride) is a common vegetative herbicide widely used globally since its introduction in the 1960s. Various antioxidants with scavenging activity, such as vitamin E, vitamin C, β-carotene, glutathione, N-acetylcysteine, melatonin, and the enzyme superoxide dismutase (SOD), have been studied and used for PQ poisoning therapy (Melchiorri et al, 1996; Suntres, 2002; Yeh et al, 2006). These antioxidant therapies yielded unsatisfactory results with respect to mortality

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