Suppressive effect of kamebakaurin on acetaminophen-induced hepatotoxicity by inhibiting lipid peroxidation and inflammatory response in mice

  • Pharmacol Rep. 2017 Oct;69(5):903-907. doi: 10.1016/j.pharep.2017.04.004.
Hiroki Yoshioka  1 ,  Yutaka Aoyagi  2 ,  Nobuyuki Fukuishi  2 ,  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 ,  Tsunemasa Nonogaki  2
Affiliations
  • 1. College of Pharmacy, Kinjo Gakuin University, Omori, Moriyamaku, Nagoya, Aichi, Japan. Electronic address: [email protected].
  • 2. College of Pharmacy, Kinjo Gakuin University, Omori, Moriyamaku, Nagoya, Aichi, Japan.
  • 3. Department of Chemistry, JiLin University, Changchun, JiLin, People's Republic of China.
  • 4. School of Pharmacy, Tokyo University of Pharmacy & Life Sciences, Horinouchi, Hachioji, Tokyo, Japan.
  • 5. Division of Health Effects Research, Japan National Institute of Occupational Safety and Health, Nagao, Tamaku, Kawasaki, Kanagawa, Japan.
PMID: 28624597 DOI: 10.1016/j.pharep.2017.04.004
Abstract

Background: Kamebakaurin (KA) is an ent-kaurane diterpenoid known to have anti-inflammatory potential. In the current study, we investigated whether pretreatment with KA could ameliorate acetaminophen (APAP)-induced hepatotoxicity by inhibiting the anti-inflammatory response in mice.

Methods: Seven-week-old C57BL/6J mice were orally administered KA or olive oil emulsion for seven days. Twenty-four hours after the last KA or olive oil administration, the mice were intraperitoneally injected with 400mg/kg APAP or saline under feed deprived condition. The mice from each group were euthanized and bled for plasma analysis 24h after the injection.

Result: APAP increased plasma levels of hepatic injury markers (i.e., alanine aminotransferase and aspartate aminotransferase), lipid peroxidation, and pro-inflammatory cytokines. Pretreatment with KA reduced the magnitude of APAP-induced increases in plasma levels of hepatic injury markers, lipid peroxidation, and inflammatory response. In addition, KA exhibited antioxidant capacity in a dose-dependent manner, with slight Reactive Oxygen Species scavenging activity.

Conclusion: Our results indicate that KA has the ability to protect the liver from APAP-induced hepatotoxicity, presumably by both inhibiting the inflammatory response and oxidative stress.

Keywords
Acetaminophen; Inflammatory response; Kamebakaurin; Oxidative stress.
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