RESUMEN
In this study, blueberry anthocyanins extract (BAE) was used to investigate its protective effect on arsenic-induced rat hippocampal neurons damage. Arsenic exposure resulted in elevated levels of oxidative stress, decreased antioxidant capacity and increased apoptosis in rat hippocampal brain tissue and mitochondria. Immunohistochemical results showed that arsenic exposure also significantly decreased the expression of mitochondrial biosynthesis-related factors PGC-1α and TFAM. Treatment with BAE alleviated the decrease in antioxidant capacity, mitochondrial biogenesis related protein PGC-1α/NRF2/TFAM expression, and ATP production of arsenic induced hippocampal neurons in rats, and improved cognitive function in arsenic damaged rats. This study provides new insights into the detoxification effect of anthocyanins on the nervous system toxicity caused by metal exposure in the environment, indicating that anthocyanins may be a natural antioxidant against the nervous system toxicity caused by environmental metal exposure.
Asunto(s)
Antocianinas , Arsénico , Arándanos Azules (Planta) , Hipocampo , Trastornos de la Memoria , Mitocondrias , Factor 2 Relacionado con NF-E2 , Neuronas , Estrés Oxidativo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Animales , Arándanos Azules (Planta)/química , Estrés Oxidativo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Arsénico/toxicidad , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Antocianinas/farmacología , Ratas , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/farmacología , Masculino , Proteínas de Unión al ADN/metabolismo , Apoptosis/efectos de los fármacos , Factores de Transcripción/metabolismo , Ratas Sprague-Dawley , Extractos Vegetales/farmacologíaRESUMEN
Chronic exposure to arsenic in drinking water damages cognitive function, and nerve cell apoptosis is one of the primary characteristics. The damage to mitochondrial structure and/or function is one of the main characteristics of apoptosis. Peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) is involved in the regulation of mitochondrial biogenesis, energy metabolism, and apoptosis. In this study, we aimed to study the role of PGC-1α in sodium arsenite (NaAsO2)-induced mitochondrial apoptosis in rat hippocampal cells. We discovered that increased arsenic-induced apoptosis in rat hippocampus increased with NaAsO2 (0, 2, 10, and 50 mg/L, orally via drinking water for 12 weeks) exposure by TUNEL assay, and the structure of mitochondria was incomplete and swollen and had increased lysosomes, lipofuscins, and nuclear membrane shrinkage observed via transmission electron microscopy. Furthermore, NaAsO2 reduced the levels of Bcl-2 and PGC-1α and increased the levels of Bax and cytochrome C expression. Moreover, correlation analysis showed that brain arsenic content was negatively correlated with PGC-1α levels and brain ATP content; PGC-1α levels were negatively correlated with apoptosis rate; and brain ATP content was positively correlated with PGC-1α levels, but no significant correlation between ATP content and apoptosis has been observed in this study. Taken together, the results of this study indicate that NaAsO2-induced mitochondrial pathway apoptosis is related to the reduction of PGC-1α, accompanied by ATP depletion.