Does dihydropyrimidine dehydrogenase level modify plasma antioxidant capacity in colorectal cancer patients treated with fluoropyrimidines?

Folia Med (Plovdiv). 2021 Oct 31;63(5):760-767. doi: 10.3897/folmed.63.e57234.

Abstract

Introduction: Colorectal cancer is the third most common cancer type worldwide. Fluoropyrimidines and their prodrug-based regimens are widely applied as primary medications. The main enzyme responsible for the rate-limiting step in pyrimidine and for the 5-fluorouracil catabolism is dihydropyrimidine dehydrogenase (DPD).

Aim: We aimed to screen DPD level and the changes of plasma antioxidant capacity of colorectal cancer patients on 5-fluorouracil regimen.

Materials and methods: Human DPD Elisa Kit based on sandwich enzyme-linked immune-sorbent assay and spectrophotometric methods (FRAP and ABTS) were used in the study.

Results: No statistically significant changes in plasma scavenging activity according to the results obtained in the ABTS system have been observed after evaluating all patients and considering DPD concentration. A decrease of the ferric reducing ability of patients' plasma taken after the administered treatment was found. The increase of DPD level is accompanied by a decrease in the p values and therefore the statistical significance of the differences increases.

Conclusions: Based on the aforementioned observations, it could be concluded that some aspects of plasma antioxidant capacity and individuals' antioxidant status might be involved in the pathogenesis of the disease and could be altered by the activity of some enzymes. The cancer therapy in question, by the specificity of its mechanism of action, can modify patient's oxidative status.

Keywords: ABTS; FRAP; colorectal cancer; dihydropyrimidine dehydrogenase; fluoropyrimidines.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antioxidants / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Dihydrouracil Dehydrogenase (NADP)* / analysis
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans

Substances

  • Antimetabolites, Antineoplastic
  • Antioxidants
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil