Kaurenoic acid extracted from Sphagneticola trilobata reduces acetaminophen-induced hepatotoxicity through inhibition of oxidative stress and pro-inflammatory cytokine production in mice |
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| Authors: | Leandro Marcondes-Alves Victor Fattori Sergio M. Borghi Yuri Lourenco-Gonzalez Allan J.C. Bussmann Elisa Y. Hirooka |
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| Affiliation: | 1. Departamento de Química, Centro de Ciências Exatas, Universidade Estadual de Londrina , Londrina, Brasil;2. Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina , Londrina, Brasil;3. Laboratório de Anatomia Patológica, Centro de Ciências de Saúde, Universidade Estadual de Londrina , Londrina, Brasil;4. Departamento de Ciência e Tecnologia de Alimentos, Centro de Ciências Agrárias, Universidade Estadual de Londrina , Londrina, Brasil |
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| Abstract: | Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug that is safe at therapeutic doses. However, acetaminophen overdose can be fatal. Currently, the only treatment available is the N-acetyl cysteine. The diterpene kaurenoic acid (ent-kaur-16-en-19-oic acid, KA) is the major constituent of Sphagneticola trilobata (L.) Pruski. KA presents anti-inflammatory, anti-nociceptive and antioxidant properties. In this study, we evaluated the efficacy of KA in a model of acetaminophen-induced hepatotoxicity. KA increased, in a dose-dependent manner, the survival rate after acetaminophen overdose. KA reduced acetaminophen-induced hepatic necrosis and ALT and AST levels. KA decreased acetaminophen-induced neutrophil and macrophage recruitment, oxidative stress and the production of IL-33, TNF-α and IL-1β, alongside with normalisation of IL-10 levels in the liver. Therefore, KA showed preclinical efficacy in acetaminophen-induced hepatotoxicity and lethality. |
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| Keywords: | Diterpene drug-induced liver injury hepatotoxicity NF-κB N-acetyl-p-aminophenol Nrf2 |
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