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. 2024 May 13;25(10):5300.
doi: 10.3390/ijms25105300.

Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies

Roberto Aquilani  1 , Silvia Brugnatelli  2 , Roberto Maestri  3 , Paolo Iadarola  1 , Salvatore Corallo  2 , Anna Pagani  2 , Francesco Serra  2 , Anna Bellini  1 , Daniela Buonocore  1 , Maurizia Dossena  1 , Federica Boschi  4 , Manuela Verri  1
Affiliations

Chemotherapy-Induced Changes in Plasma Amino Acids and Lipid Oxidation of Resected Patients with Colorectal Cancer: A Background for Future Studies

Roberto Aquilani et al. Int J Mol Sci. .

Abstract

Previous studies have documented that FOLFOX and XELOX therapies negatively impact the metabolism of skeletal muscle and extra-muscle districts. This pilot study tested whether three-month FOLFOX or XELOX therapy produced changes in plasma amino acid levels (PAAL) (an estimation of whole-body amino acid metabolism) and in plasma levels of malondialdehyde (MDA), a marker of lipid hyper oxidation. Fourteen ambulatory, resected patients with colorectal cancer scheduled to receive FOLFOX (n = 9) or XELOX (n = 5) therapy, after overnight fasting, underwent peripheral venous blood sampling, to determine PAAL and MDA before, during, and at the end of three-month therapy. Fifteen healthy matched subjects (controls) only underwent measures of PAAL at baseline. The results showed changes in 87.5% of plasma essential amino acids (EAAs) and 38.4% of non-EAAs in patients treated with FOLFOX or XELOX. These changes in EAAs occurred in two opposite directions: EAAs decreased with FOLFOX and increased or did not decrease with XELOX (interactions: from p = 0.034 to p = 0.003). Baseline plasma MDA levels in both FOLFOX and XELOX patients were above the normal range of values, and increased, albeit not significantly, during therapy. In conclusion, three-month FOLFOX or XELOX therapy affected plasma EAAs differently but not the baseline MDA levels, which were already high.

Keywords: FOLFOX and XELOX therapy; colorectal cancer; plasma amino acid changes; plasma malondialdehyde changes; potential clinical implications; primary tumor location.

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Conflict of interest statement

This study received funding (fee for publication) from Professional Dietetics S.p.A., Milano, Italy. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. No author declares any other competing interests, except for R.A. R.A. who is the scientific consultant of Professional Dietetics, Milano, Italy.

Figures

Figure 1
Figure 1
Percentage change from baseline (TA) of total amino acids in XELOXs and FOLFOXs at TB and TC. Data reported as mean (95% confidence interval). †: p = 0.03 for the comparison XELOX vs. FOLFOX at TB (Mann–Whitney U-test). Abbreviations: AAs, amino acids; TA, Time A; TB, Time B; TC, Time C.
Figure 2
Figure 2
Percentage change from baseline (TA) of essential amino acids in XELOXs and FOLFOXs at TB and TC. Data reported as mean (95% confidence interval). †: p = 0.03 for the comparison XELOX vs. FOLFOX at TB (Mann–Whitney U-test). ‡: p = 0.003 for the comparison XELOX vs. FOLFOX at TC (Mann–Whitney U-test). *: p = 0.008 for the comparison FOLFOX TC vs. TA (Wilcoxon signed rank test). Abbreviations: AAs, amino acids; TA, Time A; TB, Time B; TC, Time C.
Figure 3
Figure 3
Percentage change from baseline (TA) of branched-chain amino acids in XELOXs and FOLFOXs at TB and TC. Data reported as mean (95% confidence interval). †: p = 0.04 for the comparison XELOX vs. FOLFOX at TB (Mann–Whitney U-test). ‡: p = 0.002 for the comparison XELOX vs. FOLFOX at TC (Mann–Whitney U-test). *: p = 0.008 for the comparison FOLFOX TC vs. TA (Wilcoxon signed rank test). Abbreviations: AAs, amino acids; TA, Time A; TB, Time B; TC, Time C.
Figure 4
Figure 4
Scatterplot showing the relationship between isoleucine and lymphocyte count in XELOXs and FOLFOXs at TA. The linear regression line is also shown (red dash-dotted line). Abbreviations: TA, Time A.
Figure 5
Figure 5
Scatterplot showing the relationship between tryptophan and lymphocytes (% of TWBC) in XELOX and FOLFOX patients at TA. The linear regression line is also shown (red dash-dotted line). Abbreviations: TA, Time A; TWBC, total white blood cells.
Figure 6
Figure 6
Scatterplot showing the relationship between tryptophan and neutrophil/lymphocyte ratio in XELOX and FOLFOX patients at TA. The linear regression line is also shown (red dash-dotted line). Abbreviations: TA, Time A.
See this image and copyright information in PMC

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