Influence of feeding schedule on 24-h rhythm of hepatotoxicity induced by acetaminophen in mice

Naoya Matsunaga, Naomi Nakamura, Noriyo Yoneda, Tian Qin, Hideyuki Terazono, Hideto To, Shun Higuchi, Shigehiro Ohdo

研究成果: Article

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The influence of feeding schedule on the chronopharmacological aspects of acetaminophen (APAP) was examined in mice housed under 12-h light/dark cycle (lights on from 7:00 AM to 7:00 PM) with food and water ad libitum feeding (ALF) or under repeated time-restricted feeding (feeding time between 9:00 AM and 5:00 PM) for 2 weeks before the experiment. For the ALF group, there was a significant 24-h rhythm of mortality after APAP (600 mg/kg i.p.) injection. Peak mortality was observed after APAP injection at 9:00 PM and 1:00 AM, and nadir mortality was observed after drug injection at 9:00 AM. Hepatotoxicity after APAP (300 mg/kg i.p.) injection at 9:00 PM was significantly more severe than that after drug injection at 9:00 AM. Immunohistochemical staining using anti-APAP antibody 2 h after APAP injection was detected in centrilobular hepatocytes after drug injection at 9:00 PM but not after drug injection at 9:00 AM. CYP2E1 activity and hepatic glutathione (GSH) levels in untreated mice showed significant 24-h rhythms associated with APAP toxicity rhythm. The reduction in hepatic GSH levels after APAP injection at 9:00 PM was greater than that after drug injection at 9:00 AM. On the other hand, manipulation of the feeding schedule modified APAP hepatotoxicity rhythmicity, CYP2E1 activity, and GSH levels in the liver. Manipulation of the feeding schedule and choosing the most appropriate time of the day for drug administration may help to achieve rational chronopharmacology of some drugs including APAP in specific experimental and clinical situations.

元の言語English
ページ(範囲)594-600
ページ数7
ジャーナルJournal of Pharmacology and Experimental Therapeutics
311
発行部数2
DOI
出版物ステータスPublished - 2004 11
外部発表Yes

ASJC Scopus subject areas

  • Pharmacology

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    Matsunaga, N., Nakamura, N., Yoneda, N., Qin, T., Terazono, H., To, H., Higuchi, S., & Ohdo, S. (2004). Influence of feeding schedule on 24-h rhythm of hepatotoxicity induced by acetaminophen in mice. Journal of Pharmacology and Experimental Therapeutics, 311(2), 594-600. https://doi.org/10.1124/jpet.104.069062