Genotoxic effects and molecular docking of 1,4-dioxane: combined protective effects of trans-resveratrol.

Abstract

In this study, the protective effects of trans-resveratrol (t-resv) against 1,4-dioxane-induced toxicity in meristematic cells were investigated. For this purpose, Allium test was used and the alterations in all experimental groups were examined by using physiological, cytogenetic, biochemical, and anatomical parameters. In order to elucidate the toxicity mechanism, interactions of 1,4-dioxane and intracellular antioxidant molecules were investigated by molecular docking. As a result of the analysis, it was determined that 1,4-dioxane causes serious abnormalities in Allium cepa meristematic cells. In 1,4-dioxane-treated group, germination percentage was regressed 1.6 times, root length was reduced 12.7 times, and weight gain was decreased 7.7 times compared to control group. T-resv administration with 1,4-dioxane resulted in an improvement in physiological parameters and reduced the relative injury rate from 0.4 to 0.16. Mitotic index (MI), micronucleus (MN), and chromosomal abnormality (CAs) frequencies were investigated as cytogenetic parameters. 1,4-Dioxane decreased MI index, and increased CAs and MN frequency. In addition, it was determined by the comet test that 1,4-dioxane caused deterioration in DNA integrity. T-resv treatment was found to cause a dose-dependent improvement in genotoxic effects. Changes in the antioxidant system in all experimental groups were determined by measuring malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD), and catalase (CAT) enzyme activities. 1,4-Dioxane caused alterations in all tested parameters, causing deterioration in the oxidant/antioxidant balance in the cell. A 200-mg/L t-resv+1,4-dioxane treatment caused a 1.9-fold decrease in MDA level which is indicator of lipid peroxidation compared to only 1,4-dioxane-treated group. The mechanism of the disruption in antioxidant/oxidant dynamics and genetic integrity was elucidated by molecular docking analysis of 1,4-dioxane with antioxidant molecules and DNA. In 1,4-dioxane treatment group, anatomical changes such as cell deformation, flattened cell nucleus, and thickening of cortex cell wall were observed. The frequency of these changes decreased with t-resv administration. As a result, it was determined that 1,4-dioxane caused a versatile toxicity in A. cepa meristematic cells, while t-resv was found to have a dose-dependent protective feature against 1,4-dioxane-induced toxicity.