Thymoquinone Ingestions Reversed Inflammation Driven Glia activation and Impaired Cognitive associated behavior in Cypermethrin Exposed Rats

Abstract

Background: Pyrethroids pose health risks to humans. Therefore, it is imperative to assess the preventive benefits of thymoquinone against neurotoxicity induced by cypermethrin- in the hippocampal dentate gyrus. Methods: Forty male adult Wistar rats with an average weight of 180-200g were randomly allocated to five (5) groups, and each comprising eight rats (n=8 per group). The groups were designated as follows, through oral administrations for 14 days: 0.5ml phosphate- buffered saline (PBS) was given to group one; Group two received 20mg/kg of cypermethrin (CYM); Group three received 10 mg/kg of thymoquinone (THQ); Group four received 20 mg/kg of cypermethrin followed by 10mg/kg of thymoquinone (CYM-10mgTHQ); and Group five received 20mg/kg and 5mg/kg cypermethrin and thymoquinone respectively (CYM-5mgTHQ). Behavioral, histological, immunohistochemical, and biochemical analyses were conducted post-treatment. Results: Cypermethrin administration caused the rise in pro-inflammatory cytokine TNF-α and increased expression of astrocytes, microglia, and pro-apoptotic protein Bax. Additionally, cypermethrin reduced levels of anti-inflammatory cytokine IL-10, acetylcholinesterase (AChE) activity, and nuclear factor erythroid 2-related factor 2 (Nrf2). cytoarchitectural disruption of dentate gyrus and decreased Nrf2 expression were observed. Cognitive deficits were evident. Thymoquinone treatment attenuated TNF-α elevation, reduced astrocyte, microglial, and Bax expression, and increased IL-10, AChE, and Nrf2 levels. Conclusion: Thymoquinone demonstrated anti-inflammatory and anti-apoptotic effects against cypermethrin-induced neurotoxicity, improving cognitive function in rats.