The Potential Protective Role of Naringenin against Dasatinib-Induced Hepatotoxicity

  • Pharmaceuticals (Basel). 2023 Jun 23;16(7):921. doi: 10.3390/ph16070921.
Ahmed Z Alanazi  1 ,  Khalid Alhazzani  1 ,  Salah Q Alrewily  1 ,  Khaldoon Aljerian  2 ,  Mohammad M Algahtani  1 ,  Qamraa H Alqahtani  1 ,  Dhanush Haspula  3 ,  Abdullah S Alhamed  1 ,  Mohammed Alqinyah  1 ,  Mohammad Raish  4
Affiliations
  • 1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia.
  • 2. Department of Pathology, College of Medicine, King Saud University, Riyadh 12372, Saudi Arabia.
  • 3. Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
  • 4. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 12372, Saudi Arabia.
PMID: 37513833 DOI: 10.3390/ph16070921
Abstract

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
antioxidant; dasatinib; hepatotoxicity; inflammation; naringenin; protective effects.
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