Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 5 No. 5 October 19, 2018 p.161-165
Protection from acetaminophen-induced hepatotoxicity by post-administration of 1O, 20O-diacetyl kamebakaurin in mice
  • Hiroki Yoshioka (College of Pharmacy, Kinjo Gakuin University /
Hiroki Yoshioka 1) , Hiroyuki Ohnishi 2) , Masae Yoshikawa 1) , Ming-Yu Gui 3) , Yong-Ri Jin 3) , Xu-Wen Li 3) , Yoshiyuki Adachi 4) , Naohito Ohno 4) , Koichi Takeya 4) , Yukio Hitotsuyanagi 4) , Nobuhiko Miura 5) , Yutaka Aoyagi 1)
1) College of Pharmacy, Kinjo Gakuin University , 2) Department of Health Science, School of Allied Health Science and Graduate School of Medical Sciences, Kitasato University , 3) Department of Chemistry, JiLin University, China , 4) School of Pharmacy, Tokyo University of Pharmacy & Life Sciences , 5) Division of Health Effects Research, Japan National Institute of Occupational Safety and Health
Keywords: Acetaminophen, 1O, 20O-diacetyl kamebakaurin, Oxidative stress, Hepatic injury

Our previous study demonstrated that pre-administration of 1O, 20O-diacetyl kamebakaurin (Ac2KA) protected against acetaminophen (APAP)-induced hepatotoxicity. In the current study, we aimed to investigate whether post-administration of Ac2KA also protects against APAP-induced hepatotoxicity. Eight-week-old male C57BL/6J mice were fasted and then intraperitoneally injected with 450 mg/kg APAP or saline. At 60-min after the APAP injection, Ac2KA (50 mg/kg) or an ethanol/olive oil emulsion was orally administered. At 16-hr after the injection, the mice were killed, and blood samples were collected for plasma analysis. As a positive control, we used N-acetylcysteine (200 mg/kg, i.p.). Posttreatment with Ac2KA significantly attenuated APAP-induced plasma alanine aminotransferase and aspartate aminotransferase levels. Ac2KA administration also decreased the APAP-induced hepatic malondialdehyde concentration. Moreover, histological evaluation supported these observations. Our results show that Ac2KA exerts protective effects against APAP-induced hepatotoxicity when administered as both pretreatment and post-treatment.