Platycodin D protects acetaminophen-induced hepatotoxicity by inhibiting hepatocyte MAPK pathway and apoptosis in C57BL/6J mice - 20/09/18
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Graphical abstract |
Highlights |
• | Platycodin D (PD) exerts protective effect against APAP-induced hepatotoxicity in C57BL/6J mice. |
• | The liver protection effects of PD is due to association of alterations in MAPK signal pathway in mice. |
• | The inhibition of apoptosis and inflammation response is partly involved in the PD liver protection effects. |
Abstract |
The root of Platycodon grandiflorus (Jacq.) A. DC. (P. grandiflorus), Platycodonis Radix, has been commonly applied to prevent and treat human diseases including bronchitis, asthma and excessive phlegm. Platycodin D (PD), one of the most important therapeutic components of P. grandiflorus, has been reported to possess protective effect against alcohol and carbon tetrachloride induced hepatotoxicity. In this study, we examined the protective efficacy of PD on acetaminophen (APAP)-induced liver injury and possible underlying mechanisms in C57BL/6J mice. Administration of PD prior to APAP intoxication significantly ameliorated the increase in serum transferases, interleukin 1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), and hepatic malondialdehyde (MDA) and the depletion of glutathione (GSH) in mice. PD pretreatment decreased the expression of heme oxygenase-1 (HO-1), cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) in presence of APAP. Moreover, PD treatment noticeably reduced APAP-induced hepatocyte necrosis and apoptosis evidenced by evaluating physiological and histological hepatocyte changes in mice. Finally, PD pretreatment significantly diminished c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and p38 phosphorylation induced by APAP. Collectively, PD pretreatment effectively protects hepatocytes against APAP-induced hepatotoxicity in mice through ameliorating oxidative stress, inflammatory response, and hepatocyte apoptosis.
Le texte complet de cet article est disponible en PDF.Abbreviations : ALT, APAP, AST, COX-2, ERK1/2, GSH, HO-1, IL-1β, IL-6, JNK, MDA, NAPQI, NF-κB, PD, TNF-α
Keywords : Acetaminophen, Platycodin D, Hepatotoxicity, Oxidative stress, Apoptosis
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Vol 107
P. 867-877 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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