Cardiotoxicity of sanguinarine via regulating apoptosis and MAPK pathways in zebrafish and HL1 cardiomyocytes.
Comp Biochem Physiol C Toxicol Pharmacol
; 252: 109228, 2022 Feb.
Article
en En
| MEDLINE
| ID: mdl-34744004
ABSTRACT
Sanguinarine, a plant phytoalexin, possesses extensive biological activities including antimicrobial, insecticidal, antitumor, anti-inflammatory and anti-angiogenesis effect. But its cardiotoxicity has rarely been studied. Here, we assess the cardiotoxicity of sanguinarine in vivo using larval zebrafish from 48 hpf to 96 hpf. The results show that sanguinarine caused severe malformation and the dysfunction of the heart including reductions of heart rate, red blood cell number, blood flow dynamics, stroke volume and increase of SV-BA distance, subintestinal venous congestion. Further studies showed that apoptosis in the zebrafish heart region was observed after sanguinarine exposure using TUNEL assay and AO staining method. In addition, the genes, such as sox9b, myl7, nkx2.5 and bmp10, which play crucial parts in the development and the function of the heart, were changed after sanguinarine treatment. caspase3, caspase9, bax and bcl2, apoptosis-related genes, were also altered by sanguinarine. Further studies were performed to study the cardiotoxicity in vitro using cardiomyocytes HL1 cell line. The results showed that remarkable increase of apoptosis and ROS level in HL1 cells were induced by sanguinarine. Moreover, the MAPK pathway (JNK and P38) were notably enhanced and involved in the cardiotoxicity induced by sanguinarine. Our findings will provide better understanding of sanguinarine in the toxic effect on heart.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apoptosis
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Sistema de Señalización de MAP Quinasas
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Miocitos Cardíacos
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Benzofenantridinas
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Isoquinolinas
Límite:
Animals
Idioma:
En
Revista:
Comp Biochem Physiol C Toxicol Pharmacol
Asunto de la revista:
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2022
Tipo del documento:
Article