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

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 kgG1
, 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 kgG1
per day, administered p.o.), methotrexate (MTX) (7.5 mg kgG1
per 3 doses per week) and
low dose PQ+MTX (0.12 mg kgG1
per day p.o.+7.5 mg kgG1
per 3 doses per week) respectively for three weeks. The serum Aspartate
Transaminase (AST), Lactate Dehydrogenase (LDH), Alanine Aminotransferase (ALT), "-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-" were
measured using western blot. Results: Serum levels of AST, ALT, LDH and "-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-" 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.