Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2024.184
Hepatoprotective Effects of Resveratrol on Acetaminophen-Induced Acute Liver Injury and Its Implications for Tofacitinib Disposition in Rats
Hyeon Gyeom Choi1, So Yeon Park2, Sung Hun Bae1, Sun-Young Chang1,2 and So Hee Kim1,2,*
1College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499,
2Department of Biohealth Regulatory Science, Graduate School of Ajou University, Suwon 16499, Republic of Korea
*E-mail: shkim67@ajou.ac.kr
Tel: +82-31-219-3451, Fax: +82-31-219-3435
Received: October 10, 2024; Revised: November 13, 2024; Accepted: November 18, 2024; Published online: December 13, 2024.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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: Tofacitinib, Acute liver injury, Resveratrol, Pharmacokinetics, CYP3A1/2, CYP2C11

This Article


Cited By Articles
  • CrossRef (0)

e-submission

Archives