Continuous hypoxia attenuates paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line

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 PQinduced 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.

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

“…In this scenario, paraquat (PQ) intoxication is a serious public health problem because of its high mortality index, mainly due to the lack of an effective antidote or treatment, which is associated with its wide use even in countries where its application is forbidden. [36][37][38][39][40] One of the main mechanism for PQ toxicity is associated with the redox cycle of PQ, where formation of superoxide anion, singlet oxygen, and other reactive oxygen species (ROS) occurs. Higher levels of these ROS lead to many deleterious effects, including lipid peroxidation in cells and tissue, protein damage, and depletion of NADPH.…”

Cytoprotective Effect of Kaempferol on Paraquat-Exposed BEAS-2B Cells <i>via</i> Modulating Expression of <i>MUC5AC</i>

“…Previous studies showed that paraquat (PQ) is a potent ROS inducer in different epithelial cell lines [12][13][14] and is associated with cellular cytoxicity. However, there has been no study into whether PQ can induce MUC gene expression or not, so in this study we investigated the effects of PQ on Bronchial epithelial BEAS-2B cells.…”

“…[8][9][10][11] MUC5AC is a hallmark gene, and considered the most phenotypical gene in respiratory diseases; it accumulates in respiratory tract can lead to symptoms such as chronic cough and excessive sputum production. Previous studies showed that paraquat (PQ) is a potent ROS inducer in different epithelial cell lines [12][13][14] and is associated with cellular cytoxicity. However, there has been no study into whether PQ can induce MUC gene expression or not, so in this study we investigated the effects of PQ on Bronchial epithelial BEAS-2B cells.…”

Porous Se@SiO₂ nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

“…When these antioxidants are imbalanced, there will be airway inflammation, airway hyperresponsiveness and tissue damage, neutrophil infiltration and ultimately the formation of lung injury. 2,6,33 In our study, the results showed that the levels of ROS were markedly increased in the PQ group. In the rat model of PQ poisoning, MDA levels increased and GSH and SOD levels decreased at each time point.…”

“…In this process, PQ consumes nicotinamide adenine dinucleotide phosphate and cytochrome P450 reductase, increasing superoxide anion and hydrogen peroxide levels through the disproportionation of hydrogen peroxide to generate hydroxyl and other radicals, constituting a reactive oxygen species (ROS) system. 6 ROS can activate lipid peroxidation and increase malondialdehyde (MDA) levels in this process. The level of MDA indirectly reflects the degree of peroxidation, and elevated MDA levels can also cause cell metabolism disorders.…”