Pharmaceuticals (Jun 2023)

The Potential Protective Role of Naringenin against Dasatinib-Induced Hepatotoxicity

  • Ahmed Z. Alanazi,
  • Khalid Alhazzani,
  • Salah Q. Alrewily,
  • Khaldoon Aljerian,
  • Mohammad M. Algahtani,
  • Qamraa H. Alqahtani,
  • Dhanush Haspula,
  • Abdullah S. Alhamed,
  • Mohammed Alqinyah,
  • Mohammad Raish

DOI
https://doi.org/10.3390/ph16070921
Journal volume & issue
Vol. 16, no. 7
p. 921

Abstract

Read online

Dasatinib (DASA) is a novel tyrosine kinase inhibitor, approved for leukemia treatment. However, the long-term use of DASA induces several complications, especially liver damage. On the other hand, Naringenin (NGN) is a potent antioxidant and anti-inflammatory agent which is known to exert protective effects in several liver disease animal models. Yet, the effect of NGN on DASA-induced hepatotoxicity has not been examined. This study investigated the hepatoprotective effects of NGN against DASA-induced acute liver injury, using a mouse model. The mice were given NGN (50, 100, and 200 mg/kg po) or saline for 7 days, followed by DASA on the eighth day (25 mg/kg p.o.). DASA treatment alone was found to cause overexpression of proinflammatory cytokines, such as interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and malonyl aldehyde (MDA), whereas attenuation of antioxidant genes including superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx). Interestingly, a pretreatment with NGN + DASA resulted in minimizing the proinflammatory mediators and restoring the levels of antioxidant genes. In addition, there was evidence of necro-inflammatory changes in histopathological findings in the liver samples after DASA administration which remarkably reduced with NGN + DASA. Thus, this study revealed that NGN could minimize the hepatotoxicity induced by DASA by providing anti-inflammatory and antioxidant protection.

Keywords