Morin attenuates neurobehavioural deficits, hippocampal oxidative stress, inflammation, and apoptosis in rats co-exposed to bisphenol S and diethyl phthalate

• DOI: 10.1016/j.brainres.2022.148068
• Publication Date: 2022-08-27T10:53:59Z
• Authors: Emmanuel Ifeanyic...; Oluwatosin Adebis...; Ofem Effiom Eteng; Ceaser Antiya Moses; Chukwuka Uzoamaka...; Adewale Segun James; Abdulwasiu Oladok...; Mohammed Emmanuel...; Florence Ajasa; Oluwakemi Olawuyi; Regina Ngozi Ugbaja
• Keywords: Flavonoids; Inflammation; Male; 0301 basic medicine; Phthalic Acids; Apoptosis; Hydrogen Peroxide; Flavones; Hippocampus; Antioxidants; Rats; 3. Good health; Oxidative Stress; 03 medical and health sciences; Phenols; Animals; Sulfones; Rats, Wistar

Endocrine-disrupting pollutants (EDPs) remain pervasive in the environment. Bisphenol S (BPS) and diethyl phthalates (DEP) are commonly used to replace the more toxic EDPs. However, it is unclear if they induce neurotoxicity, like their predecessors. Morin possesses relevant neuro-pharmacological activities. Hence, we sought to evaluate the protective effects of morin against the neurotoxic effects previously reported for EDPs. Male Wistar rats were exposed to a mixture of BPS and DEP (MBD) and treated with morin for 21 days. Behavioural assessments were conducted, and the hippocampal tissues were processed for analysis. Rats exposed to MBD presented anxiety-like behaviours, impaired cognitive and motor functions compared to the control group. MBD exposure induced hyperactivity of neurosignalling enzymes (AChE, ADA, MAO-A) and depleted hippocampal antioxidants (SOD, CAT, GPx, and GSH). MBD exposure increased calcium levels and inhibited total Ca2+-ATPase activity. Levels of reactive species (NO and H2O2) and oxidative damage markers (MDA and AOPP) were significantly (P < 0.05) elevated compared to control. The hippocampal expressions of IL-1β, TNFα, BAX, and APAF-1 in the MBD-exposed rats were significantly higher compared to control. Correspondingly, NF-κB and caspase-3 pathways were activated in the hippocampus of MBD-exposed rats, while the expressions of IL-10 and BDNF were repressed. However, co-treatment with morin improved the neurobehavioral outcomes, alleviated the hyperactivity of neurosignalling enzymes, while suppressing hippocampal oxidative stress, inflammation, and apoptosis. Histological and stereological evaluations supported these findings. In conclusion, co-exposure to BPS and DEP elicit similar neurotoxic outcomes as their predecessors, while morin confers marked protection against these outcomes.