Zafirlukast and vincamine ameliorate tamoxifen-induced oxidative stress and inflammation: Role of the JNK/ERK pathway.
Life Sci
; 202: 78-88, 2018 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-29626531
ABSTRACT
AIMS:
This study investigated the hepatoprotective effects of both zafirlukast and vincamine and their possible role in the treatment of tamoxifen-induced liver injury in rats. MATERIALS ANDMETHODS:
Female Wistar rats were divided into five groups (10 rats each). Groups I and II received 1% Tween 80 and served as normal and tamoxifen controls, respectively. Groups III, IV and V were treated with zafirlukast (80â¯mg/kg), vincamine (10â¯mg/kg) and a combination of zafirlukast (80â¯mg/kg) and vincamine (10â¯mg/kg), respectively for 10 successive days. Tamoxifen was given orally to all groups, except for 1st group, in the dose of 45â¯mg/kg for 10â¯days to induce liver injury. Subsequently, rats were sacrificed for biochemical, histopathological, Immunohistochemistry, PCR and western blot assessment. KEYFINDINGS:
Tamoxifen-induced liver injury was reflected by alterations in estimated biochemical parameters, activation of JNK/ERK pathway, increased expression of NF-κB, liver oxidative stress and inflammatory markers parallel to histopathological changes in liver tissue. Treatment of rats with zafirlukast and vincamine ameliorated tamoxifen induced hepatic cell injury via suppressing oxidative stress, inflammatory markers, caspases-3, p-JNK/p-ERK and NF-κB pathways.SIGNIFICANCE:
Zafirlukast and vincamine may be regarded as potential therapeutic strategies with antioxidant and anti-inflammatory activities against tamoxifen-induced oxidative damage in rat liver.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Compostos de Tosil
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Vasodilatadores
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Vincamina
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Anti-Inflamatórios não Esteroides
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Estresse Oxidativo
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Antagonistas de Leucotrienos
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Sistema de Sinalização das MAP Quinases
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Proteínas Quinases JNK Ativadas por Mitógeno
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Antagonistas de Estrogênios
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2018
Tipo de documento:
Article