Thymoquinone inhibits Neuroinflammatory mediators and vasoconstriction injury via NF-κB dependent NeuN/GFAP/Ki-67 in hypertensive Dams and F1 male pups on exposure to a mixture of Bisphenol-A analogues.

Abstract

Bisphenol-A (BPA) analogues seem inevitable components of numerous domestic products, but these have been identified as agents of teratogenic disorders. This study, therefore, investigated the effect of thymoquinone (TMQ) on the striatum of hypertensive female rats and their F1 male offsprings, on exposure to a mixture of Bisphenol-B, Bisphenol-F and Bisphenol-S (MBFS). Female rats were divided into normotensive and hypertensive groups; and both were treated with MBFS only, MBFS + TMQ, and TMQ only. Exposure to MBFS and co-treatment with TMQ lasted at least 63 days. Neurobehavioural assessments were conducted using Open Field (OF). A spectrophotometer was used for cholinergic, dopaminergic and adenosinergic enzyme assays; Real-Time PCR for gene expression; and immunohistochemistry for protein quantification; while H&E, cresyl fast violent, and congo red stains were used for histological assessments. From the results, maternal exposure to MBFS mediated striatal dysfunction via p53 and NF-kB upregulation; decreased BCl-2, Ki-67 and NeuN; increased GFAP, nissl bodies and β-amyloid. Dysregulation of cholinergic, dopaminergic and adenosinergic enzymes in addition to decreased nitric oxide levels were also associated with MBFS toxicity. Hypertension was found to exacerbate MBFS toxicity. From OF test; increased anxiety and decreased psychomotor activity were associated with maternal exposure to MBFS. However, co-treatment with thymoquinone prevented striatal dysfunction in hypertensive dams and their F1 male offspring. In conclusion, disruption of the delicate balance between apoptosis and cell proliferation culminating in the reduction of mature neurons is responsible for neurodegeneration and neuropathy associated with MBFS exposure. However, these can be prevented through regular consumption of natural products and supplements rich in thymoquinone.