Pro-Neurogenic and Antioxidant Efficacy of Nigella sativa Oil Reduced Vulnerability Cholinesterase Dysfunction and Disruption in Amygdala-Dependent Behaviours in Chlorpyrifos Exposure

Background: Organophosphorus Pesticides (OPs) are compounds with irreversible cholinesterase activity which induce cholinergic neurotoxicity, but still remain a widely used pesticide in household and agriculture. Aim and Objectives: This study investigated the efficacy of a natural antioxidant Nigella sativa Oil (NSO) against Chlorpyrifos (CPF) induced oxidative stress and implications on emotionality behaviours. Material and Methods: Thirty-two adult Wistar rats were randomly divided into four groups, and exposed to (1 ml/kg b w) of normal saline, (14.9 mg/kg b w) of CPF, (14.9 mg/kg b w) of CPF plus (1 ml/kg b w) of NSO and (1 ml/kg b w) of NSO respectively for 14 consecutive days. Body weight were recorded at day 1 and 15 of the experiment, the rats were exposed to trials in both Open Field Test (OFT) and Elevated Plus Maze (EPM) to asses anxiety-like behaviours and fear related learning respectively on the 13th day. Rats were euthanized by the 15th day, the brains excised, and the amygdala area of brains were removed, homogenized to analyse for total Reactive Oxygen Species (ROS), Nitrous Oxide (NO) levels and Acetylcholinesterase (AChE) activities, while the other three were processed for histology (Nissl stain) and Proliferative marker (Ki67 immunohistochemistry). Results: Repeated CPF exposure caused an increase in NO and ROS levels, reduction in AChE activities and a loss in the neurogenic cells in the amygdala. It was also a prolonged freezing period, centre squares avoidance and delayed transfer latency with CPF exposure. However, NSO prevented the overproduction of ROS and NO, and markedly reactivated AChE activities in the amygdala either with or without CPF exposure. NSO treatment was also, able to preserve neurogenic cells in the amygdala and subsequently improved amygdala-dependent behaviours in the treated rats. Conclusion: The antioxidant efficacy of NSO could be efficacious in CPF induced neuro-cognitive toxicity in rats

Nigella sativa conserved hippocampal oxidative and neurogenic activities to salvage neuro-cognitive integrities in chlorpyrifos insult

Chlopyrifos (CPF) is an organophosphate, implicated in brain damage and cognitive deficits, whose consistence deposit in the environment has contributed to the toxicity burdens of xenobiotics. This study investigated the efficacy of Nigella sativa oil (NSO) against CPF insults on the hippocampus. Thirty-two rats were randomly divided into four groups of eight rats each, exposed to 1 ml/kg of Normal saline, 14.9 mg/kg of CPF, 14.9 mg/kg of CPF plus 1 ml/kg of NSO and 1 ml/kg of NSO respectively for 14 consecutive days. The rats were exposed to 3 trials each on the 11–13 days in the Morris water maze, and subsequently latency to hidden platform and time in the platform quadrant were recorded as measures of long term memory (LTM), short term memory (STM) and reference memory (RM) on the 14th day. The rats were euthanized on day 15, the brains excised, and the hippocampus of five brains removed, homogenized to analyze for total reactive oxygen species (ROS), nitric oxide (NO) levels and acetylcholinesterase (AChE) activities, while the other three were processed for histology and Ki67 immunohistochemistry. CPF caused a marked increase in hippocampal NO and ROS activities, depleted AChE activities and Ki67 expressions, delayed escape latency and reduced visit to the platform quadrant. Intervention with NSO depleted ROS/NO levels, improved neurogenic proteins, AChE activities and neuro-cognitive markers depletions in CPF exposure. Altogether, our findings showed that NSO is a potential therapeutic drug for the treatment of CPF-induced cognitive deficit through its antioxidant property and adult neurogenesis in rats. Keywords: Nigella sativa oil, Organophosphates, Oxidative damage, Acetylcholinesterase, Cognitio

Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats

The execution of agricultural activities on an industrial scale has led to indiscriminate deposition of toxic xenobiotics, including organophosphates, in the biome. This has led to intoxication characterized by deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to a combination of two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP), on neuro-cognitive performance and anxiety-like behaviors in rats. Thirty-two adult male Wistar rats (150⁻170 g) were randomly divided into four groups, orally exposed to normal saline (NS), DDVP (8.8 mg/kg), CPF (14.9 mg/kg), and DDVP + CPF for 14 consecutive days. On day 10 of exposure, anxiety-like behavior and amygdala-dependent fear learning were assessed using open field and elevated plus maze paradigms, respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following three training trials on days 11, 12, and 13. On day 15, the rats were euthanized, and their brains excised, with the hippocampus and amygdala removed. Five of these samples were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three were processed for histology (cresyl violet stain) and proliferative markers (Ki67 immunohistochemistry). Marked (p ≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p ≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damage are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning