Anticancer Effects of Vaccinium arctostaphylos L. through HOTAIR/miR-124/Notch1 Axis of Hepatocellular Carcinoma in Rat: A Biochemical, Molecular, Immunohistochemical, and Histopathological Approaches

ABSTRACT

Background and Purpose: We investigated the effectiveness of Vaccinium arctostaphylos L. fruit extract (VAFE) in protecting hepatocytes against N-diethylnitrosamine (DEN)-related hepatocellular carcinoma (HCC) by exploring its impact on biochemical, molecular, and antioxidant pathways, as well as its role in regulating the HOTAIR/miR-124/Notch1 axis pathway. Materials and Methods: In the present study, 50 Wistar rats in 5 groups (n = 10/group) of normal, HCC (80 mg/kg DEN), HCC rats receiving 200 and 400 mg/kg DEN + VAFE, and normal rats receiving 400 mg/kg VAFE were divided. The serum concentrations of liver function indices (bilirubin, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, C-reactive protein, and alkaline phosphatase), inflammatory cytokines (interleukin (IL)-1β, IL-10, tumor necrosis factor-α, and IL-6) and oxidants parameters (catalase, superoxide dismutase, and glutathione peroxidase enzyme activity and nitric oxide levels) were measured. Liver tissue HOTAIR, miR‐124, Notch1, and Jagged1 genes and proteins were measured. p53-positive cells of liver hepatocytes were evaluated by immunohistochemical technique. Results: DEN induced significant changes in body and liver weight, serum liver enzymes, antioxidant levels, inflammatory markers, and HOTAIR/miR-124/Notch1 axis genes/proteins expression related to liver pathways. VAFE demonstrated dose-dependent effects in countering these changes, significantly improving weight, liver health, antioxidant capacity, and inflammatory responses, especially at 400 mg/kg. The histopathological evaluation showed improvements in liver tissue structure with VAFE treatment. Conclusion: Overall, our study demonstrates the administration of VAFE can anticancer effects of DEN-induced HCC.

KEYWORDS

• Vaccinium arctostaphylos L
• N-diethylnitrosamine
• HOTAIR
• liver
• hepatocellular carcinoma

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• DOI10.1177/09731296241264620Copy

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