1O, 20O-diacetyl kamebakaurin protects against acetaminophen-induced hepatotoxicity in mice.

1O, 20O-diacetyl kamebakaurin protects against acetaminophen-induced hepatotoxicity in mice.
Biomed Res. 2018;39(5):251-260
Authors: Yoshioka H, Nonogaki T, Ohnishi H, Fukuishi N, Yoshikawa M, Gui MY, Jin YR, Li XW, Adachi Y, Ohno N, Takeya K, Hitotsuyanagi Y, Miura N, Aoyagi Y
Abstract
The present study aimed to investigate the protective effects of kamebakaurin (KA) and 1O, 20O-diacetyl kamebakaurin (Ac2KA) on acetaminophen (APAP)-induced hepatotoxicity and compare the hepatoprotective mechanisms of the two chemicals. Seven-week-old male C57BL/6J mice were orally administered KA, Ac2KA, or an ethanol/olive oil emulsion once per day for 7-days. Twenty-four hours after the final administration, the mice were fasted and then intraperitoneally injected with 450 mg/kg APAP or saline. At 16 h after injection, the mice were euthanized and blood samples were collected for plasma analysis. Pretreatment with KA and Ac2KA significantly attenuated APAP-induced hepatic injury. The protective effect of Ac2KA was stronger than that of KA. These two chemicals attenuated oxidative stress, inflammatory cytokine production, c-jun N-terminal kinase activation, and receptor-interacting protein (RIP)-3 activation. Ac2KA also decreased APAP-induced RIP-1 activation and nuclear factor kappa B (NF-κB) p65 translocation. Moreover, Ac2KA repressed mRNA expression of Cyp1a2/2e1 in the liver. Our results showed that KA and Ac2KA exerted protective effects aga...

Source: Biomed Res - October 19, 2018 Category: Research Authors: Yoshioka H, Nonogaki T, Ohnishi H, Fukuishi N, Yoshikawa M, Gui MY, Jin YR, Li XW, Adachi Y, Ohno N, Takeya K, Hitotsuyanagi Y, Miura N, Aoyagi Y Tags: Biomed Res Source Type: research