Orally administered Thymoquinone mitigates cypermethrin-induced dentate gyrus oxidative stress, preventing GABAergic interneuron degeneration and memory impairment in rats via the Nrf2/ARE pathway.

Abstract

<title>Abstract</title> Background Exposure to chemical toxins, including insecticides, has harmful effects on body organs such as the brain. This study examined the neuroprotective of thymoquinone on the cypermethrin's harmful effects on the histoarchitecture of the dentate gyrus as well as motor deficit. Methods Forty adult male rats (180-200g) were randomly divided into 5 groups (n = 8 per group). Groups I, II, III, and IV received oral administration of 0.5 ml of phosphate buffered saline, 20 mg/kg of cypermethrin, 10 mg/kg of thymoquinone, 20 mg/kg cypermethrin plus 5 mg/kg of thymoquinone, and 20 mg/kg of cypermethrin plus 10 mg/kg of thymoquinone for 14 days respectively. The novel Object recognition test assesses intermediate-term memory at days 14 and 21 of the experiment. At the end of these treatments, the animals were euthanized and taken for cytoarchitectural analysis and immunohistochemical studies. Result The study shows that thymoquinone at 5 and 10 mg/kg improved Novelty preference and discrimination index. Thymoquinone enhanced Nissl body integrity, increased GABBAergic interneuron expression, nuclear factor erythroid 2-derived factor 2, and enhanced Bcl-2 expression in the dentate gyrus. It also improved the concentration of nuclear factor erythroid 2-derived factor 2, increased the activities of superoxide dismutase and glutathione, and decreased the concentration of malondialdehyde level against cypermethrin-induced neurotoxicity. Conclusion thymoquinone could be a therapeutic agent against cypermethrin poisoning.