Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Cancer Research and Molecular Biology Laboratory, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Mycotoxin Res. 2023 Feb;39(1):67-80. doi: 10.1007/s12550-023-00474-6. Epub 2023 Jan 26.
Populations in malaria endemic areas are frequently exposed to mycotoxin-contaminated diets. The possible toxicological outcome of co-exposure to dietary aflatoxin B (AFB) and artemisinin-based combination therapy warrants investigation to ascertain amplification or attenuation of cellular injury. Here, we investigated the neurobehavioral and biochemical responses associated with co-exposure to anti-malarial drug coartem, an artemether-lumefantrine combination (5 mg/kg body weight, twice a day and 3 days per week) and AFB (35 and 70 µg/kg body weight) in rats. Motor deficits, locomotor incompetence, and anxiogenic-like behavior induced by low AFB dose were significantly (p < 0.05) assuaged by coartem but failed to rescue these behavioral abnormalities in high AFB-dosed group. Coartem administration did not alter exploratory deficits typified by reduced track plot densities and greater heat map intensity in high AFB-dosed animals. Furthermore, the reduction in cerebral and cerebellar acetylcholinesterase activity, anti-oxidant enzyme activities, and glutathione and thiol levels were markedly assuaged by coartem administration in low AFB group but not in high AFB-dosed animals. The significant attenuation of cerebral and cerebellar oxidative stress indices namely reactive oxygen and nitrogen species, xanthine oxidase activity, and lipid peroxidation by coartem administration was evident in low AFB group but not high AFB dose. Although coartem administration abated nitric oxide level, activities of myeloperoxidase, caspase-9, and caspase-3 in animals exposed to both doses of AFB, these indices were significantly higher than the control. Coartem administration ameliorated histopathological and mophometrical changes due to low AFB exposure but not in high AFB exposure. In conclusion, contrary to AFB alone, behavioral and biochemical responses were not altered in animals singly exposed to coartem. Co-exposure to coartem and AFB elicited no additional risk but partially lessened neurotoxicity associated with AFB exposure.
在疟疾流行地区，人群经常接触到受真菌毒素污染的食物。联合暴露于膳食黄曲霉毒素 B（AFB）和基于青蒿素的联合疗法可能会产生毒性作用，需要进行调查以确定细胞损伤的放大或减弱。在这里，我们研究了联合使用抗疟药物 Coartem（一种青蒿素-咯萘啶合剂，每天两次，每次 5mg/kg 体重，每周 3 天）和 AFB（35 和 70μg/kg 体重）对大鼠的神经行为和生化反应的影响。低剂量 AFB 引起的运动功能障碍、运动失调和焦虑样行为显著（p<0.05）减轻了 Coartem 的作用，但未能挽救高剂量 AFB 组的这些行为异常。Coartem 给药并没有改变高剂量 AFB 组动物的探索缺陷，表现为轨迹图密度降低和热图强度增加。此外，Coartem 给药显著减轻了低剂量 AFB 组大脑和小脑乙酰胆碱酯酶活性、抗氧化酶活性、谷胱甘肽和巯基水平的降低，但在高剂量 AFB 组动物中没有这种作用。Coartem 给药显著减轻了大脑和小脑氧化应激指标的活性，如活性氧和氮物种、黄嘌呤氧化酶活性和脂质过氧化，这在低剂量 AFB 组中是明显的，但在高剂量 AFB 组中则不然。尽管 Coartem 给药降低了暴露于两种剂量 AFB 的动物的一氧化氮水平，但髓过氧化物酶、caspase-9 和 caspase-3 的活性仍然高于对照组。Coartem 给药改善了由于低剂量 AFB 暴露引起的组织病理学和形态学变化，但在高剂量 AFB 暴露时则没有。总之，与单独暴露于 AFB 相比，单独暴露于 Coartem 的动物的行为和生化反应没有改变。联合暴露于 Coartem 和 AFB 没有增加风险，但部分减轻了与 AFB 暴露相关的神经毒性。
