1. Academic Validation
  2. Isoliquiritigenin prevents Doxorubicin-induced hepatic damage in rats by upregulating and activating SIRT1

Isoliquiritigenin prevents Doxorubicin-induced hepatic damage in rats by upregulating and activating SIRT1

  • Biomed Pharmacother. 2022 Feb;146:112594. doi: 10.1016/j.biopha.2021.112594.
Wahidah H Al-Qahtani 1 Ghedeir M Alshammari 2 Jamaan S Ajarem 3 Amani Y Al-Zahrani 1 Aishah Alzuwaydi 1 Refaat Eid 4 Mohammed Abdo Yahya 1
Affiliations

Affiliations

  • 1 Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia.
  • 2 Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh, Saudi Arabia. Electronic address: aghedeir@ksu.edu.sa.
  • 3 Department of Zoology, College of Sciences, King Saud University, Riyadh, Saudi Arabia.
  • 4 Department of Pathology, College of Medicine, King Khalid University, Abha, Saudi Arabia.
Abstract

This study evaluated if the hepatic protective effect of Isoliquiritigenin (ISL) against doxorubicin (DOX)-treated rats involves upregulating sirtuin-1 (SIRT1) signaling. Adult male was divides into 5 groups (n = 6 rats/each) as control (vehicle), ISL (25 mg/kg), DOX (15 mg/kg), DOX + ISL, and DOX + ISL + EX-527 (a SIRT1 Inhibitor, 5 mg/kg). ISL and EX-527 were administered 10 days before and after the single treatment of DOX. Also, cultured AML-12 hepatocytes (5 ×104) were treated with 10 µM of ISL for 24 h with or without DOX-treatments (10 µM) and in the presence or absence of EX-527 (5 µM). ISL prevented hepatocyte damage and decreased serum levels of hepatic transaminases, hepatic levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and hepatic mRNA levels of Bax and caspases-3,8, and 9. In the liver of the control and DOX-treated rats, ISL reduced levels of malondialdehyde (MDA) but increased hepatic levels of glutathione (GSH), superoxide dismutase (SOD), and catalase, as well as mRNA levels of Bcl2. In vitro, ISL stimulated cell survival and lowered levels of ROS but increased GSH levels. In vivo and in vitro, in the livers of control and DOX-treated Animals, ISL significantly increased the nuclear activity and mRNA levels of SIRT1, enhanced the nuclear levels of Nrf2, and reduced nuclear levels of NF-κB p65. In conclusion, ISL alleviates DOX-induced hepatocyte toxicity by stimulating the Nrf2/antioxidants axis and concomitant suppression of NF-κB, mainly by upregulating/activating SIRT1.

Keywords

Doxorubicin; Hepatotoxicity; Isoliquiritigenin; Nrf2; SIRT1.

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