Antioxidant attenuation of ROS-involved cytotoxicity induced by Paraquat on HL-60 cells

Abstract

The cytotoxic effects of Paraquat, an herbicide refractory to treatment after intentional or accidental contact, were investigated on the human leukemia HL-60 cells. With the establishment of Paraquat injury model of HL-60 cells, trypan blue exclusion assaying was performed to have determined the effects of Paraquat-induced cytotoxicity on HL-60 cells in a concentration- dependent manner. Upon treatment with various concentrations of Paraquat, pronounced increase on the levels of intracellular production of O2?- and H2O2 was detected with employment of fluorescent probes. Indicative of the oxidative stress, levels of MDA and T-AOC were quantitated to have determined the causal role for Paraquat in subjecting HL-60 cells to oxidative damage. Based on this finding, effects of antioxidant enzymes including GSH, NAC, CAT and SOD on attenuating the Paraquat-induced oxidative damage on HL-60 cells were examined, aiming to identify the most effective antioxidant enzyme for alleviating the cytotoxicity induced by Paraquat. In conjunction with the determination of cytotoxicity exerted by all the antioxidant enzymes on HL-60 cells, GSH-with its least inherent cytotoxicity on HL-60 cells-was identified as a promising candidate ingredient for extenuating the Paraquat-induced cytotoxicity

Glycolate combats massive oxidative stress by restoring redox potential in Caenorhabditis elegans

“…Firstly, we quantified H 2 O 2 levels upon exposure of C. elegans larvae to PQ 2+ . In agreement with previous reports 26 – 28 , treatment of C. elegans larvae with the herbicide induced a dramatic elevation of H 2 O 2 (Fig. 1c ).…”

An engineered cell line lacking OGG1 and MUTYH glycosylases implicates the accumulation of genomic 8-oxoguanine as the basis for paraquat mutagenicity

“…Previous studies have shown that cells deficient in Ogg1 and Mutyh are sensitive to oxidants, in part because of the negative effects of oxidative stress on cell-cycle progression [3]. These observations are in accord with studies showing that increased levels of ROS are associated with cell death [22, 42, 43], as well as DNA damage [44]. There should be a substantial increase in ROS levels when cells are severely repair-deficient.…”

“…Previous studies have documented the ability of PQ to redox cycle resulting in generation of ROS and extensive mitochondrial damage [17–19]. Among the different ROS, the superoxide anion radical, has been observed and reported [2, 19–22]; H 2 O 2 has also been observed being induced in a dose-dependent manner [22, 42, 43]. ROS-dependent cell death was also reported in other cultured mammalian cells, such as human promyelocytic leukemia HL-60 cells [22], RAW264.7 cells [42], and human neutrophils [43].…”