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Item Diphenyl diselenide abrogates brain oxidative injury and neurobehavioural deficits associated with pesticide chlorpyrifos exposure in rats(Elsevier B.V., 2018) Adedara, I. A. || || || || || ||; Owoeye, O.; Awogbindin, I. O.; Ajayi, O. B.; Adeyemo, O. A.; Rocha, J. B. T.; Farombi, E. O.Exposure to pesticide chlorpyrifos (CPF) is associated with neurodevelopmental toxicity both in humans and animals. Diphenyl diselenide (DPDS) is a simple synthetic organoselenium well reported to possess antioxidant, anti-inflammatory and neuroprotective effects. However, there is paucity of information on the beneficial effects of DPDS on CPF-mediated brain injury and neurobehavioural deficits. The present study investigated the neuroprotective mechanism of DPDSin rats sub-chronically treated with CPF alone at 5 mg/kg body weight or orally co-treated with DPDS at 2.5 and 5 mg/kg body weight for 35 consecutive days. Endpoint analyses using video- tracking software in a novel environment revealed that co-treatment with DPDS significantly (p < 0.05) pro- tected against CPF-mediated locomotor and motor deficits precisely the decrease in maximum speed, total distance travelled, body rotation, absolute turn angle, forelimb grip strength as well as the increase in negative geotaxis and incidence of fecal pellets. The enhancement in the neurobehavioral activities of rats co-treated with DPDS was verified by track plot analyses. Besides, DPDS assuaged CPF-induced decrease in acetylcholinesterase and antioxidant enzymes activities and the increase in myeloperoxidase activity and lipid peroxidation level in the mid-brain, cerebral cortex and cerebellum of the rats. Histologically, DPDS co-treatment abrogated CPF- mediated neuronal degeneration in the cerebral cortex, dentate gyrus and cornu ammonis3 in the treated rats. In conclusion, the neuroprotective mechanisms of DPDS is related to the prevention of oxidative stress, enhance- ment of redox status and acetylcholinesterase activity in brain regions of the rats. DPDS may be a promising chemotherapeutic agent against brain injury resulting from CPF exposure.Item Neurobehavioral and biochemical changes in Nauphoeta cinerea following dietary exposure to chlorpyrifos(Elsevier Inc., 2016) Adedara, I. A.; Rosemberg, D. B.; Souza, D.; Farombi, E. O.; Aschner, M.; Souza, D. O.; Rocha, J. B. T.The present study aimed to increase our understanding about the mode of toxic action of organophosphate pesticides in insects by evaluating the biochemical and neurobehavioral characteristics in Nauphoeta cinerea exposed to chlorpyrifos (CPF)-contaminated diet. The insects were exposed for 35 consecutive days to CPF at 0.078, 0.15625, 0.3125 and 0.625 μg/g feed. Locomotor behavior was assessed for a 10-min trial in a novel arena and subsequently, biochemical analyses were carried out using the cockroaches’ heads. In comparison to control, CPF-exposed cockroaches showed significant decreases in the total distance traveled, body rotation, turn angle and meandering, along with significant increase in the number of falls, time and episodes of immobility. The marked decrease in the exploratory profiles of CPF-exposed cockroaches was confirmed by track plots, whereas occupancy plot analyses showed a progressive dispersion at 0.15625 μg/g feed group. Moreover, the heads of CPF-exposed cockroaches showed marked decrease in acetylcholinesterase activity and antioxidant status with concomitant significant elevation in dichlorofluorescein oxidation and lipid peroxidation levels in CPF-treated cockroaches. Gas Chromatography–Mass Spectrometry analyses revealed bioaccumulation of CPF in cockroaches exposed to concentrations above 0.078 μg/g feed. The findings from this investigation showed N. cinerea as a value model organism for the risk assessment of environmental organophosphate contamination in insects.Item Influence of diphenyl diselenide on chlorpyrifos-induced toxicity in Drosophila melanogaster(Elsevier GmbH., 2015) Adedara, I. A.; Klimaczewski, C. V.; Barbosa, N. B. V.; Farombi, E. O.; Souza, D. O.; Rocha, J. B. T.Exposure to chlorpyrifos (CPF) poses several harmful effects to human and animal health. The present study investigated the influence of diphenyl diselenide (DPDS) on CPF-induced toxicity in Drosophila melanogaster. Firstly, the cumulative responses of virgin flies (2- to 3-day-old) to CPF (0.075–0.6 µg/g) and DPDP (5–40 µmol/kg) in the diet for 28 consecutive days were investigated. Subsequently, the protective effect of DPDS (10, 20 and 40 µmol/kg) on CPF (0.15 µg/g)-induced mortality, locomotor deficits, neurotoxicity and oxidative stress was assessed in a co-exposure paradigm for 7 days. Results showed that CPF exposure significantly decreased the operant reflex in a time- and concentration-dependent manner, whereas the percent live flies with DPDS treatment was not statistically different from control following 28 days of treatment. In the co-exposure study, CPF significantly increased mortality while the survivors exhibited significant locomotor deficits with decreased acetylcholinesterase (AChE) activity. Dietary supplementation with DPDS was associated with marked decrease in mortality, improvement in locomotor activity and restoration of AChE activity in CPF-exposed flies. Moreover, CPF exposure significantly decreased catalase and glutathione-S-transferase activities, total thiol level with concomitant significant elevation in levels of reactive oxygen species and thiobarbituric acid reactive substances in the head and body regions of the treated flies. Dietary supplementation with DPDS significantly improved the antioxidant status and prevented CPF-induced oxidative stress, thus demonstrating the protective effect of DPDS in CPF-treated flies.Item Biochemical and behavioral deficits in the lobster cockroach Nauphoeta cinerea model of methylmercury exposure(The Royal Society of Chemistry, 2015) Adedara, I. A.; Rosemberg, D. B..; Souza, D. O.; Kamdem, J. P.; Farombi, E. O.; Aschnerd, M.; Rocha, J. B. T.Methylmercury (MeHg) is well-known for its neurodevelopmental effects both in animals and in humans. As an alternative to utilizing conventional animal models, this study evaluated behavioral and biochemical parameters using the nymphs of the lobster cockroach Nauphoeta cinerea. Animals were exposed to MeHg at 0, 0.03125, 0.0625, 0.125, 0.25 and 0.5 mg per g feed for 35 consecutive days. Locomotor activity and exploratory profiles were analyzed using video-tracking software during a 10 minute trial. Subsequently, biochemical estimations were carried out using cockroach heads. MeHg exposure caused behavioral impairment as evidenced by a significant decrease in distance travelled, time spent walking, turn angle and body rotation. The marked decrease in the exploratory profiles of MeHg-exposed cockroaches was confirmed by track plots, whereas occupancy plot analyses revealed a gradual dispersal in homebase formation, starting from 0.0625 mg per g feed. Biochemically, MeHg exposure significantly decreased acetylcholinesterase activity (AChE), an enzyme which plays a pivotal role in neurotransmission. Moreover, MeHg caused increased oxidative stress as evidenced by decreased total thiol levels and glutathione S-transferase (GST) activity, along with increased 2’,7’-dichlorofluorescein (DFCH) oxidation and thiobarbituric acid reactive substance (TBARS) production. In conclusion, these data demonstrated that Nauphoeta cinerea mimics the behavioral and biochemical deficits observed in rodents exposed to MeHg, thus highlighting its validity as an alternative model for basic toxicological studies.
