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International Journal of Pharmacology

Year: 2022  |  Volume: 18  |  Issue: 2  |  Page No.: 354 - 362

Protective Effect of Glucose-6-Phosphate Dehydrogenase and Dihydrofolate Reductase Against Diethylnitrosamine-Induced Hepatocellular Carcinoma in Rats

Khalid Saad Alharbi, Muhammad Afzal, Imran Kazmi, Sami I. Alzarea, Nasser Hadal Alotaibi, Sattam Khulaif Alenezi, Ameeduzzafar Zafar and Nabil K. Alruwaili

Abstract

Background and Objective: Antineoplastic acts by numerous mechanisms and have variability in action on healthy and cancerous cells. To examine the protective effect of Glucose-6-Phosphate Dehydrogenase (G6PD) and Dihydrofolate Reductase (DHFR) in Diethylnitrosamine (DENA) induced hepatocellular carcinoma in rats. Materials and Methods: A total of 30 healthy male divided into 5 groups (n = 6): Group 1 rats entitled normal controls, rats of Group 2 was serving as disease controls and exposed to a single dose of DENA (200 mg kg–1, IP). Group 3, 4 and 5 were treatment groups that were subjected to DENA administration as scheduled in group-2 and treated with primaquine (PQ) (0.21 mg kg–1 per day, administered p.o.), methotrexate (MTX) (7.5 mg kg–1 per 3 doses per week) and low dose PQ+MTX (0.12 mg kg–1 per day p.o.+7.5 mg kg–1 per 3 doses per week) respectively for three weeks. The serum Aspartate Transaminase (AST), Lactate Dehydrogenase (LDH), Alanine Aminotransferase (ALT), α-fetoprotein levels were estimated. In liver tissue, levels of Catalase (CAT), Glutathione (GSH) and Malondialdehyde (MDA) were estimated. The levels of NF-κB, Bcl-2 and IkB-α were measured using western blot. Results: Serum levels of AST, ALT, LDH and α-fetoprotein elevated significantly in group 2 animals which were found maintained in treatment animals. The levels of antioxidant enzymes level of NF-κB, Bcl-2 and I κB-α were also altered in disease control group animals which were restored in treated animals. Results of group 5 were more consistent and satisfactory. Conclusion: The lower dose combination therapy with an inhibitor of G6PD and DHFR can successfully manage toxicities associated with methotrexate and may reduce the dose of methotrexate to a safer level.

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