Alpha-mangostin attenuates the apoptotic pathway of abamectin in the fetal rats’ brain by targeting pro-oxidant stimulus, catecholaminergic neurotransmitters, and transcriptional regulation of reelin and nestin

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.

Keywords:

• Abamectin
• Alpha-mangostin
• Fetal rats’ brain
• Reelin
• Nestin
• Apoptosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Khairy A. Ibrahim and Mohammed Eleyan contributed to the study conception and design, material preparation, data collection, and analysis. Mohammed Eleyan and Basim M. Ayesh acquired the first draft of the manuscript. Soad A. Khwanes and Rania A. Mohamed contributed to the data analysis. Khairy A. Ibrahim contributed to the obtained data interpretation writing, review, and editing of the manuscript. All authors read and approved the final version of the manuscript.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.