Cantharidin-induced acute hepatotoxicity: the role of TNF-α, IKK-α, Bcl-2, Bax and caspase3.
J Appl Toxicol
; 40(11): 1526-1533, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32627230
ABSTRACT
Cantharidin is of high medicinal value but has strong toxicity. Nowadays, multiple research has focused on the mechanism of its antitumor activity while research on toxicological profiles associated with cantharidin poisoning is still limited. Its hepatotoxicity has attracted attention recently for the crucial role of the liver in detoxification. Here, we aim to find a potential mechanism for cantharidin-induced acute hepatotoxicity with a view to assisting subsequent research or clinical use or detoxification. Twenty-one male Sprague-Dawley rats were randomly divided into control, low-dose (1.34 mg/kg) and high-dose (2.67 mg/kg) cantharidin exposure groups. We used hematoxylin-eosin to observe pathological changes and used immunofluorescent staining, western blotting and real-time quantitative polymerase chain reaction to detect the expression of the markers. The main pathological changes in livers of cantharidin-treated rats were necrosis, inflammatory infiltration and hemorrhage. We found coexpression of tumor necrosis factor alpha (TNF-α), IkappaB kinase-alpha (IKK-α) and caspase3 by immunofluorescent staining in livers of cantharidin-treated rats. Compared with the control, the levels of TNF-α, IKK-α and caspase3 increased significantly in the experimental groups (P < .05). The ratio of B-cell lymphoma-2 (Bcl-2)/Bax increased in the low-dose group but decreased in the high-dose group (P < .05). Cantharidin exposure raised IKK-α mRNA and caspase3 mRNA levels (P < .05). In conclusion, the participation of TNF-α, IKK-α, Bcl-2, Bax and caspase3 uncovered a novel mechanism underlying cantharidin-induced acute hepatotoxicity, and the mechanism needs to be studied further.
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MEDLINE
Assunto principal:
Cantaridina
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Fator de Necrose Tumoral alfa
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Proteínas Proto-Oncogênicas c-bcl-2
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Quinase I-kappa B
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Caspase 3
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Doença Hepática Induzida por Substâncias e Drogas
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En
Ano de publicação:
2020
Tipo de documento:
Article