Abstract

Abamectin, an avermectin member, can induce significant neurodegeneration symptoms in non-target organisms. However, its neurodevelopmental influences in mammals are unclear. Here, we focus on the antiapoptotic action of alpha-mangostin against the developmental neurotoxicity of abamectin with the possible involvement of reelin and nestin mRNA gene expression. Thirty–two pregnant rats were allocated to four groups (8 rats/group); control, alpha-mangostin (20 mg/kg/d), abamectin (0.5 mg/kg), and co-treated group (alpha-mangostin + abamectin). The animals have gavaged their doses during the gestation period. The fetotoxicity and many signs of growth retardation were observed in the abamectin-intoxicated rats. In comparison with the control group, abamectin prompted a significant elevation (p < 0.05) in the levels of malondialdehyde and nitric oxide, along with many symptoms of histopathological changes in the fetal cerebral cortex. However, the glutathione, dopamine, and serotonin concentrations together with the activities of glutathione-S-transferase, catalase, and superoxide dismutase were markedly decreased (p < 0.05) in the abamectin group. Moreover, abamectin remarkably upregulated (p < 0.05) the brain mRNA gene expression of reelin, nestin, and caspase-9 as well as the immunoreactivity of Bax and caspase-3 proteins in the cerebral cortex. It should be noted that alpha-mangostin mitigated the developmental neurotoxicity of abamectin to the normal range by recovering the levels of oxidant/antioxidant biomarkers, catecholamines; and apoptosis-related proteins with the involvement of reelin and nestin genes regulation. Those records revealed that the transcription regulation of reelin and nestin could be involved in the neuroprotective efficacy of alpha-mangostin, especially avermectin's developmental neurotoxicity.

摘要

阿维菌素是一种阿维菌素成员，可在非靶标生物体中诱发显着的神经变性症状。然而，它对哺乳动物的神经发育影响尚不清楚。在这里，我们专注于 alpha-mangostin 对阿维菌素发育神经毒性的抗凋亡作用，可能涉及 reelin 和巢蛋白 mRNA 基因表达。将 32 只妊娠大鼠分配到 4 组（8 只大鼠/组）；对照组、α-山竹素 (20 mg/kg/d)、阿维菌素 (0.5 mg/kg) 和联合治疗组 (α-山竹素 + 阿维菌素)。这些动物在妊娠期间灌胃了它们的剂量。在阿维菌素中毒的大鼠中观察到胎儿毒性和许多生长迟缓的迹象。与对照组相比，阿维菌素显着升高（p < 0.05) 的丙二醛和一氧化氮水平，以及胎儿大脑皮层组织病理学变化的许多症状。然而，阿维菌素组的谷胱甘肽、多巴胺和血清素浓度以及谷胱甘肽-S-转移酶、过氧化氢酶和超氧化物歧化酶的活性显着降低（p  < 0.05）。此外，阿维菌素显着上调（p < 0.05) reelin、nestin 和 caspase-9 的脑 mRNA 基因表达以及大脑皮层中 Bax 和 caspase-3 蛋白的免疫反应性。应该注意的是，α-山竹素通过恢复氧化剂/抗氧化剂生物标志物儿茶酚胺的水平，将阿维菌素的发育神经毒性减轻至正常范围；以及与reelin和nestin基因调控有关的凋亡相关蛋白。这些记录表明，reelin 和巢蛋白的转录调控可能与 α-山竹素的神经保护功效有关，尤其是阿维菌素的发育神经毒性。