Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats

  • Hyeon Gyeom Choi (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • So Yeon Park (Department of Biohealth Regulatory Science, Graduate School of Ajou University) ;
  • Sung Hun Bae (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • Sun-Young Chang (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • So Hee Kim (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University)
  • Received : 2024.10.10
  • Accepted : 2024.11.18
  • Published : 2025.05.01
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Abstract

Tofacitinib, which is used to treat rheumatoid arthritis (RA), is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, CYP3A1/2 and CYP2C11. Acetaminophen (APAP), which is frequently used for pain relief in patients with RA, can induce acute liver injury (ALI) when taken in excess, profoundly affecting drug metabolism. Resveratrol (RVT) is a polyphenolic compound with hepatoprotective properties. This study investigated the protective effects of RVT against APAP-induced ALI in rats, and explored its influence on the pharmacokinetics of tofacitinib. In ALI rats, both intravenous and oral administration of tofacitinib resulted in a significant (207% and 181%) increase in the area under the plasma concentration-time curve (AUC), primarily driven by a substantial reduction (66.1%) in non-renal clearance (CLNR) compared to that in control (CON) rats. Notably, RVT administration in ALI rats provided effective liver protection, partially restoring liver function, as evidenced by normalized glutamate oxaloacetate transaminase levels and the pharmacokinetic parameters, AUC and CLNR, closer to those observed in untreated CON rats (117% and 81.9%, respectively). These findings highlight the importance of considering the potential interactions between RVT or polyphenol-rich natural products and medications in patients with ALI in clinical practice.

Keywords

Acknowledgement

This work was partly supported by the Basic Science Research Program through a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) (NRF-2021R1A2C1011142) and by the GRRC program of Gyeonggi province (GRRCAjou2023-B04), Korea.

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