Akpa Amaka Rosita, Ayo Joseph Olusegun, Mika'il Hudu Garba, Zakari Friday Ocheja
Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.
Department of Veterinary Physiology, Faculty of Veterinary Medicine, Ahmadu Bello University, Zaria, Nigeria.
Toxicol Res. 2020 Jul 7;37(2):163-171. doi: 10.1007/s43188-020-00049-y. eCollection 2021 Apr.
Chlorpyrifos (CPF), a chlorinated organophosphate insecticide that is widely used in agriculture and public health, has neurotoxic effects in animals. In addition to acetylcholinesterase inhibition, CPF has been shown to induce alterations such as oxidative stress and lipid peroxidation. Fisetin is a dietary flavonol that protects the brain tissue against oxidative stress by modulating the activity of antioxidant enzymes. This study was designed to investigate the protective role of fisetin against brain oxidative damages and neurobehavioral parameters induced by subchronic oral exposure to CPF in albino mice. Adult albino mice (males, n = 32, weighing 20 ~ 25 g) were assigned randomly into 4 groups and treated accordingly for 7 weeks as follows: Group 1(S/OIL): served as the control group and were given 2 ml/kg of soya oil; Group 2 (CPF): received CPF (6.6 mg/kg; 1/5th of the LD); Group 3 (FIS): fisetin (15 mg/kg) and Group 4 (FIS + CPF): received fisetin at 15 mg/kg, followed by CPF (6.6 mg/kg) 30 min later. Co-treatment with FIS + CPF mitigated the increase in brain malondialdehyde concentration (0.28 ± 0.02 nmol/mg) and orchestrated the increase in the activities of catalase (81.35 ± 7.26 µ/mg), superoxide dismutase (93.03 ± 6.63 IU/mL), glutathione peroxidase (68.76 ± 3.554 nmol/mL) and acetylcholinesterase (11.59 ± 0.72 nmol/min/mL) when compared to the CPF group. The result showed that deficits in motor strength and excitability scores induced by subchronic CPF were mitigated by fisetin administration. It was concluded that fisetin has a protective potential in mitigating against oxidative stress and damages in the brain tissues, induced by subchronic exposure to CPF in adult male albino mice.
毒死蜱（CPF）是一种广泛应用于农业和公共卫生领域的有机氯杀虫剂，对动物具有神经毒性作用。除抑制乙酰胆碱酯酶外，CPF还可诱导氧化应激和脂质过氧化等改变。非瑟酮是一种膳食黄酮醇，可通过调节抗氧化酶的活性来保护脑组织免受氧化应激。本研究旨在探讨非瑟酮对白化病小鼠亚慢性口服CPF诱导的脑氧化损伤和神经行为参数的保护作用。将成年白化病小鼠（雄性，n = 32，体重20~25 g）随机分为4组，并按以下方式相应处理7周：第1组（S/OIL）：作为对照组，给予2 ml/kg大豆油；第2组（CPF）：接受CPF（6.6 mg/kg；LD的1/5）；第3组（FIS）：非瑟酮（15 mg/kg），第4组（FIS+CPF）：先接受15 mg/kg非瑟酮，30分钟后再接受CPF（6.6 mg/kg）。与CPF组相比，FIS+CPF联合处理减轻了脑丙二醛浓度（对照组为0.28±0.02 nmol/mg）的升高，并协调了过氧化氢酶（81.35±7.26 μ/mg）、超氧化物歧化酶（93.03±6.63 IU/mL）、谷胱甘肽过氧化物酶（68.76±3.554 nmol/mL）和乙酰胆碱酯酶（11.59±0.72 nmol/min/mL）活性的升高。结果表明，给予非瑟酮可减轻亚慢性CPF诱导的运动强度和兴奋性评分缺陷。得出的结论是，非瑟酮在减轻成年雄性白化病小鼠亚慢性接触CPF所诱导的脑组织氧化应激和损伤方面具有保护潜力。
