Hiroki Yoshioka1, Yutaka Aoyagi2, Nobuyuki Fukuishi2, Ming-Yu Gui3, Yong-Ri Jin3, Xu-Wen Li3, Yoshiyuki Adachi4, Naohito Ohno4, Koichi Takeya4, Yukio Hitotsuyanagi4, Nobuhiko Miura5, Tsunemasa Nonogaki2. 1. College of Pharmacy, Kinjo Gakuin University, Omori, Moriyamaku, Nagoya, Aichi, Japan. Electronic address: h-yoshioka@kinjo-u.ac.jp. 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.
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.
BACKGROUND:Kamebakaurin (KA) is an ent-kauranediterpenoid 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.