Perioperative GLY-GLN Infusion Diminishes the Surgery-Induced Period of Immunosuppression

Exner, Ruth; Tamandl, Dietmar; Goetzinger, Peter; Mittlböck, Martina; Fuegger, Reinhold; Sautner, Thomas; Spittler, Andreas; Roth, Erich

doi:10.1097/00000658-200301000-00015

Cited by 53 publications

(14 citation statements)

References 33 publications

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“…19,96 Therapeutic effects of these combined nutrients are dose and end point dependent and may also rely on severity of the illness, timing, and duration. 97–99 …”

Section: Discussionmentioning

confidence: 99%

Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω‐3 Polyunsaturated Fatty Acids

Xue

Denkinger

Schlotzer

et al. 2015

J Parenter Enteral Nutr

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Background Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX-induced cardiotoxicity forms the major cumulative dose-limiting factor. Glutamine and ω-3 polyunsaturated fatty acids (PUFAs) are putatively cardioprotective during various stresses and/or have potential chemosensitizing effects during cancer chemotherapy. Methods Antitumor activity and cardiotoxicity of DOX treatment were evaluated simultaneously in a MatBIII mammary adenocarcinoma tumor-bearing rat model treated with DOX (cumulative dose 12 mg/kg). Single or combined treatment of parenteral glutamine (0.35 g/kg) and ω-3 PUFAs (0.19 g/kg eicosapentaenoic acid and 0.18 g/kg docosahexaenoic acid) was administered every other day, starting 6 days before chemotherapy initiation until the end of study (day 50). Results Glutamine alone significantly prevented DOX-related deterioration of cardiac function, reduced serum cardiac troponin I levels, and diminished cardiac lipid peroxidation while not affecting tumor inhibition kinetics. Single ω-3 PUFA treatment significantly enhanced antitumor activity of DOX associated with intensified tumoral oxidative stress and enhanced tumoral DOX concentration while not potentiating cardiac dysfunction or increasing cardiac oxidative stress. Intriguingly, providing glutamine and ω-3 PUFAs together did not consistently confer a greater benefit; conversely, individual benefits on cardiotoxicity and chemosensitization were mostly attenuated or completely lost when combined. Conclusions Our data demonstrate an interesting differentiality or even dichotomy in the response of tumor and host to single parenteral glutamine and ω-3 PUFA treatments. The intriguing glutamine × ω-3 PUFA interaction observed draws into question the common assumption that there are additive benefits of combinations of nutrients that are beneficial on an individual basis.

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“…19,96 Therapeutic effects of these combined nutrients are dose and end point dependent and may also rely on severity of the illness, timing, and duration. 97–99 …”

Section: Discussionmentioning

confidence: 99%

Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω‐3 Polyunsaturated Fatty Acids

Xue

Denkinger

Schlotzer

et al. 2015

J Parenter Enteral Nutr

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“…Glutamate can be hydrolyzed by glutamine through glutamine phosphatase. Studies showed that glutamate affected the proliferation of lymphocytes, the immune response of monocytes/macrophages, and the synthesis of Hsp 70 (Exner et al, 2003). Glycine is the smallest of the amino acids and consists of a single carbon molecule attached to an amino acid and a carboxyl group.…”

Section: Amino Acids Metabolismmentioning

confidence: 99%

Comparative analysis between aerial parts and roots (Astragali Radix) of astragalus membranaceus by NMR-based metabolomics

Wang

Jin

et al. 2017

Food and Agricultural Immunology

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Aerial parts of Astragalus membranaceus (APAM), which are derived from the overground part of Astragalus membranaceus consist of stems and leaves. The aim of this study was to provide a scientific basis for the comprehensive utilization of APAM. Nuclear magnetic resonance (NMR) was used to compare the chemical compositions of APAM and Astragali Radix (AR). The pharmacological effects of APAR and AR in cyclophosphamide (Cy)-induced mice were studied using 1 H NMR-based metabolomics. The results showed that APAM and AR were different from each other in primary and secondary metabolites, and they could recover the amounts of white blood cell, monocytes, lymphocyte and neutrophils content, IL-2 and IL-6; there was no significant difference in APAM and AR in terms of immune functions. The mechanisms of APAM and AR on leucopenia were probably related to energy metabolism, amino acids metabolism, and gut microbiota-related metabolism. ARTICLE HISTORY

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“…Lowering glutamine in vitro to 0.2 mM reduces phagocytosis [8], decreases antigen and HLA-DR presentation, and diminishes cytokine production [9]. In recent in-vivo studies it was shown that correcting plasma glutamine levels by glutamine supplementation in patients undergoing elective surgery was associated with a diminished decrease in HLA-DR [10], and with increased TNF-a production in response to ex-vivo lipopolysaccharide stimulation [11]. Maintaining plasma glutamine levels thus seems not only to be essential for the monocyte energy status but also for their function, and is therefore important for the inflammatory response.…”

Section: Metabolism and Function Of Glutaminestarving Cellsmentioning

confidence: 99%

Regulative capacity of glutamine

Oehler

Roth

2003

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Perioperative GLY-GLN Infusion Diminishes the Surgery-Induced Period of Immunosuppression

Abstract: In this study perioperative infusion of GLY-GLN reduced immunosuppression. The effect of GLN-containing dipeptides seems to be different when administered in glycine or alanine form.

Cited by 53 publications

References 33 publications

Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω‐3 Polyunsaturated Fatty Acids

Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω‐3 Polyunsaturated Fatty Acids

Comparative analysis between aerial parts and roots (Astragali Radix) of astragalus membranaceus by NMR-based metabolomics

Regulative capacity of glutamine

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