Isomers and their metabolites of endosulfan induced cytotoxicity and oxidative damage in SH-SY5Y cells

Abstract

As an organochlorine insecticide, endosulfan has been widely banned or restricted, but it is still largely used in many developing countries. Previous studies have shown multiple adverse health effects of endosulfan. However, the neurotoxicity of endosulfan has not been fully elucidated. In this study, endosulfan isomers (α-/β-endosulfan) and their major metabolites (endosulfan sulfate, endosulfan diol, and endosulfan lactone) were, respectively, exposed to human neuroblastoma SH-SY5Y cells. Results showed that both α-endosulfan and β-endosulfan caused decrease of cell viability and morphological damages in a dose-dependent manner. Their median effective concentrations (EC50s) were respectively 79.6 μM (α-endosulfan) and 50.37 μM (β-endosulfan) for 72 h exposure. EC50s of α/β-endosulfan mixture were lower than that of the single isomer. However, EC50s of its metabolites were higher than that of technical endosulfan. Endosulfan and its metabolites caused increases of reactive oxygen species and the lipid peroxidation, but decrease of superoxide dismutase in a dose-dependent manner. These results indicate that α-endosulfan exhibits higher neurotoxicity than β-endosulfan. Mixture of endosulfan isomers shows stronger cytotoxicity than the single isomer. After endosulfan is degraded, cytotoxicity of its metabolites decreases gradually. The neurotoxicity of endosulfan and its metabolites is closely related to oxidative damage and antioxidative deficit.

Low-dose endosulfan inhibits proliferation and induces senescence and pro-inflammatory cytokine production in human lymphocytes, preferentially impacting cytotoxic cells

“…It is also important to note that in those experiments and the work here, ENDO had to be dissolved in DMSO (the latter is known to impart significant effects on the immune system/immune cells). As other studies reported no effect of DMSO when diluted to between 0.1 and 1.0% Enhui et al 2016;Ghosh et al 2018), in all the experiments here, the final DMSO level presented to cells ranged from 0.0004% to 0.07%…”

Effects of endosulfan isomers on cytokine and nitric oxide production by differentially activated RAW 264.7 cells

“…These results suggest that endosulfan-α has a higher cytotoxic potency than endosulfan-β in RAW 264.7 cells. Opposite cytotoxic potencies were found for these endosulfan isomers by Enhui et al [ 14 ] who used a tetrazolium reduction assay to show endosulfan-β to be more cytotoxic than endosulfan-α in a human neuroblastoma cell line [ 10 ]. These results suggest that the toxicity of endosulfan isomers varies with the cell type examined.…”

“…These results suggest that the toxicity of endosulfan isomers varies with the cell type examined. Technical grade endosulfan products, or other mixtures of α and β endosulfans, have been examined extensively for cytotoxic potential [ [7] , [8] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] ]. Not surprisingly, these studies have shown that endosulfan exposure in vitro causes loss of cell viability that increases in severity as the concentration and duration of exposure increases.…”

Mechanism of acute endosulfan intoxication-induced neurotoxicity in Sprague-Dawley rats / Mehanizam akutne neurotoksičnosti u Sprague-Dawley štakora izazvane trovanjem endosulfanom

“…In human neuroblastoma SH-SY5Y cells, endosulfan isomers and their major metabolites induced intracellular accumulation of ROS and lipid peroxidation by suppressing activities of antioxidant enzymes (13,14). In Wistar albino rats, endosulfan significantly increased the levels of tissue MDA and plasma 8-OHdG, an indicator of oxidative DNA damage, which were effectively restored by a treatment with melatonin (28).…”

“…The imbalance between ROS formation and antioxidant capacity occurs in various physiological and pathological conditions such as inflammation, aging, cancer, drug-induced toxicity, and drug addiction (12). Although the neurotoxic mechanism of endosulfan is not yet fully understood, except for its GABA antagonistic and ATPase-inhibiting functions, the study outcomes of organochlorine pesticides from in vitro cell cultures (13,14) and in vivo animal models (15) imply that the oxidative damages may play an important role in the acute neurotoxicity of endosulfan. Therefore, in this study the neurotoxic mechanism of endosulfan was investigated focusing on the oxidative stress by analysing ROS levels, antioxidant defence capacity, and oxidative damages to critical macromolecules such as proteins and lipids.…”