Endosulfan induces cardiotoxicity through apoptosis via unbalance of pro-survival and mitochondrial-mediated apoptotic pathways.
Sci Total Environ
; 727: 138790, 2020 Jul 20.
Article
en En
| MEDLINE
| ID: mdl-32344260
Although the associations between endosulfan and adverse cardiovascular health have been reported, the toxic effects and underlying mechanism of endosulfan on the heart are not well understood. In this study, we examined the cardiotoxicity induced by endosulfan using Wistar rats and human cardiomyocytes (AC16) cells. Wistar rats were divided into control group (received corn oil alone) and three concentrations of endosulfan groups (1, 5 and 10 mg/kg·bw) by gavage. The AC16 cells were treated with three various concentrations (0, 1.25, 5, and 20 µg/mL) of endosulfan. The results showed that endosulfan induced cytotoxicity through damaging myocardial structure, decreasing the viability of cardiomyocytes, and elevating the serum levels of cardiac troponin I, heart fatty acid binding protein, aspartate aminotransferase, and reactive oxygen species (p < 0.05). Moreover, measurement of mitochondrial function showed that endosulfan could significantly decrease adenosine triphosphate levels and cytochrome c oxidase IV expression in AC16 cells (p < 0.05). In addition, endosulfan obviously inhibited Bcl-2 expression, activated the expressions of cytochrome c/Caspase-9/Caspase-3 signaling pathway, and induced the apoptosis of AC16 cells (p < 0.05). Furthermore, endosulfan significantly increased the expression of Bim, and inhibited the expressions of PI3K/Akt/FoxO3a signaling pathways in cardiomyocytes (p < 0.05). These results suggest that endosulfan may induce cardiotoxicity by inducing myocardial apoptosis resulting from activation of mitochondria-mediated apoptosis pathway and inhibition of pro-survival signaling pathways, which might be helpful in elucidating the mechanism of cardiac dysfunction induced by endosulfan.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfatidilinositol 3-Quinasas
/
Endosulfano
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Total Environ
Año:
2020
Tipo del documento:
Article
Pais de publicación:
Países Bajos