P19-29 Impact of Bisphenol A, S, and F on the Liver: Individual and Combined Effects on Oxidative Markers in Rats

Bisphenol A (BPA) and its substitutes bisphenol S (BPS) and bisphenol F (BPF) are endocrine disrupting chemicals widely used in the production of polycarbonate plastics, epoxy resins and thermal paper. These chemicals have been associated with many human diseases, such as reproductive and endocrine disorders, diabetes, obesity, cardiovascular, chronic respiratory and kidney diseases, cancers, etc. Their impact on the liver, an essential organ for detoxification and metabolism, has raised concerns, as bisphenols may induce oxidative damage and alter liver function. Therefore, the aim of this study was to examine the potential of BPA, BPS and BPF individually, as well as in combinations of two or all three bisphenols, to induce oxidative stress in the liver following subacute oral exposure in rats. Female Wistar rats (n=40) were randomly divided into eight groups (5 rats per group): one control and seven treated. The control group received deionized water by oral gavage, while the treated groups were given individual doses of BPA (0.26 µg/kg/day), BPS (0.60 µg/kg/day), and BPF (0.68 µg/kg/day), combinations of two bisphenols, and a mixture of all three bisphenols (MIX). The doses applied reflect the real-life human exposure to bisphenols. After 28 days, the rats were euthanized, their livers were isolated, and homogenization of the tissue was performed. Parameters of redox status were determined: the activity of the enzyme superoxide dismutase (SOD), total sulfhydryl groups (SH), glutathione levels (GSH), malondialdehyde (MDA) and ischemia-modified albumin (IMA). Significant differences in oxidative stress markers were observed in treated compared to the control group. IMA and MDA are pro-oxidative markers, and their increases indicate oxidative stress. IMA levels showed a significant increase with BPA alone and all mixture groups, with the highest increase observed in the BPA+BPF group, while MDA levels significantly increased in the MIX group. SH groups were significantly reduced in the BPF, BPA+BPF, and MIX groups. GSH levels were significantly decreased in all bisphenol groups and mixtures, with the most pronounced decrease in the BPA and BPA+BPF groups. Additionally, SOD activity was significantly reduced in all groups treated with individual bisphenols, as well as in those receiving BPA+BPS and the MIX group. Along with the decrease in SH groups and GSH levels, this indicates the depletion of antioxidant protection reserves in the tissue. These findings suggest that bisphenols, both individually and in combinations, induce oxidative stress in the liver through increase IMA and MDA, while they decrease SH groups, GSH levels and SOD. Co-exposure to two or more bisphenols generally induced more pronounced disturbances in redox status in the liver compared to individual compounds, with the BPA+BPF and MIX groups showing the most marked oxidative effects. (No. 451-03-65/2024-03/200161)