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Toxics 2018, 6(4), 71; https://doi.org/10.3390/toxics6040071

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

1
Neuroscience Unit, Department of Anatomy, College of Health Sciences, University of Ilorin, P.M.B 1515, Ilorin 240003, Nigeria
2
Comparative Neurobiology Unit, School of Anatomical sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa
3
Neurophysiology Unit, Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B 1515, Ilorin 240003, Nigeria
4
Department of Anatomy and Physiology, Faculty of Medicine, National University of Science and Technology, Bulawayo 0000, Zimbabwe
5
Institute of Neuroscience, National Yang-Ming University, Shih-Pai, Taipei 11221, Taiwan
6
Department of Anatomy, Olabisi Onabanjo University, Ago-iwoye, Ogun State, Nigeria
7
Department of Human Anatomy, Faculty of Basic Medical Sciences, Federal University of Dutse, PMB 7156, Dutse, Jigawa State, Nigeria
8
Endocrinology and metabolism Research Unit, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria
*
Author to whom correspondence should be addressed.
Received: 16 October 2018 / Revised: 21 November 2018 / Accepted: 27 November 2018 / Published: 1 December 2018
(This article belongs to the Collection Xenobiotics in Developmental Neurotoxicity)
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Abstract

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. View Full-Text
Keywords: oxidative damage; organophosphates; neurotoxicity; spatial working memory; anxiety-related behaviors oxidative damage; organophosphates; neurotoxicity; spatial working memory; anxiety-related behaviors
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Imam, A.; Sulaiman, N.A.; Oyewole, A.L.; Chengetanai, S.; Williams, V.; Ajibola, M.I.; Folarin, R.O.; Muhammad, A.S.; Shittu, S.-T.T.; Ajao, M.S. Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats. Toxics 2018, 6, 71.

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