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Abstract
Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and occurs frequently in patients with liver cirrhosis. HCC is the leading cause of cancer-related mortality around the globe.
Aim: This study assessed the effects of thiamin in the anticancer activity of methotrexate (MTX) in diethyl nitrosamine (DEN) induced hepatocellular Carcinoma in Wistar strain male rats.
Method: Fifty rats were randomly segregated in five groups with 10 rats in each group. HCC was induced by single intraperitoneal (i.p) dose of DEN (200 mg/kg) and HCC promoter phenobarbital was used in the basal diet (0.05%) for 5 days per week until the termination of the study in all the rats except for the normal control (NC) group. Disease control (DC) was given no treatment, while DM (DEN + MTX) and DT (DEN + thiamin) groups were given MTX (5 mg/kg, i.p per week for 16 weeks) and thiamin (25 mg/kg, orally, daily for 16 weeks), respectively. DMT (DEN + MTX + thiamin) group was given the combined dose of MTX and thiamin. Histopathological study was carried out to confirm the liver function tests such as α-feto protein (AFP), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TB), and total protein (TP) along with antioxidants vascular endothelial growth factor (VEGF), lipid per-oxidation (LPO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT).
Results: Results showed that liver biomarkers and antioxidants parameters were still abnormal in the DC group while DM group showed significant restoration, but DT group showed less significant normalization. DMT showed mild recovery of these parameters.
Conclusion: The mechanism of action of MTX and thiamin is antiparallel to each other and hence their concomitant administration may lead to inefficient anticancer activity of MTX.
Acknowledgment
The authors acknowledge with thanks DSR for technical and financial support.
Disclosure Statement
The authors declare that they have no conflict of interest.
Funding
This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, under grant no. (G: 432-156-1440).
Author's Contribution
Shakir Saleem: Conceptualization, investigation, methodology, validation, writing-original draft, writing review, and editing. Imran Kazmi: Data curation, formal analysis, methodology, validation, writing review, and editing. Aftab Ahmad: Conceptualization, data curation, formal analysis, funding acquisition, investigation, project administration, resources, supervision, writing review, and editing. Mohammad F Abuzinadah: Formal analysis, resources, supervision, validation, visualization, writing review and editing. Ali Samkari: Data analysis, writing review, and editing. Huda M Alkrathy: Investigation, data analysis, writing review, and editing. Ruqaiyah Khan: Conceptualization, data curation, formal analysis, investigation, methodology, resources, supervision, validation, visualization, writing-original draft, writing review, and editing.