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.

Autor: Ibrahim KA; Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Giza, Egypt., Eleyan M; Department of Laboratory Medical Sciences, Al-Aqsa University, Gaza, Palestine., Khwanes SA; Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Giza, Egypt., Mohamed RA; Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Giza, Egypt., Ayesh BM; Department of Laboratory Medical Sciences, Al-Aqsa University, Gaza, Palestine.
Jazyk: angličtina
Zdroj: Drug and chemical toxicology [Drug Chem Toxicol] 2022 Nov; Vol. 45 (6), pp. 2496-2508. Date of Electronic Publication: 2021 Aug 01.
DOI: 10.1080/01480545.2021.1960856
Abstrakt: 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.
Databáze: MEDLINE
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