Effect of glutamine on glutathione, IGF-I, and TGF-β1

Anita T. Johnson, Yihong Cao Kaufmann, Shaoke Luo, Valentina Todorova, Vicki Klimberg

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background. Our previous results have showed that oral glutamine (GLN) supplementation decreased carcinogenesis in 7,12-dimethylbenz[a]antracene (DMBA) breast cancer model. We also have found that GLN raises blood glutathione (GSH) levels in an implantable breast cancer model. The process of tumor growth was accompanied by depressed GSH production and increased levels of insulin-like growth factor-I (IGF-I) and transforming growth factor β1 (TGF-β1). GSH is counter-regulatory to IGF-I. We therefore hypothesized that in DMBA model of breast cancer, the increased GSH levels seen with oral GLN would be associated with lowered levels of IGF-I &TGF-β1. Methods. Time-dated pubertal Sprague-Dawley rats were gavaged at time 0 with 1 g/kg/day glutamine (GLN) (n = 18), isonitrogenous Freamine (FA) (n = 18), or water (H2O) (n = 18). Rats were further randomized on day 7 to 100 mg/kg DMBA or oil. After 14 days, the animals were sacrificed and blood GSH, IGF-1, TGF-β1, breast tissue, and gut mucosa GSH levels were measured. Results. Oral GLN increased significantly blood, breast tissue, and gut mucosa levels of GSH in both DMBA and control groups in comparison with the control groups not treated with GLN. At the same time, the levels of blood IGF-I and TGF-β1 decreased significantly in both DMBA-treated and control groups. DMBA did not significantly affect any of these levels. Conclusions. Oral GLN increased GSH levels and lowered IGF-I and TGF-β1 in a range that is considered clinically significant. However, the effect of GLN in maintaining normal gut GSH production in the presence of DMBA was much more significant. Inconsistent with our hypothesis, reduction in IGF and TGF-β1 levels did not correlate with DMBA's effect on gut GSH production.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalJournal of Surgical Research
Volume111
Issue number2
DOIs
StatePublished - May 15 2003
Externally publishedYes

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9,10-Dimethyl-1,2-benzanthracene
Transforming Growth Factors
Glutamine
Insulin-Like Growth Factor I
Glutathione
Breast Neoplasms
Control Groups
Mucous Membrane
Breast
Sprague Dawley Rats
Oils
Carcinogenesis
Water
Growth

ASJC Scopus subject areas

  • Surgery

Cite this

Effect of glutamine on glutathione, IGF-I, and TGF-β1. / Johnson, Anita T.; Kaufmann, Yihong Cao; Luo, Shaoke; Todorova, Valentina; Klimberg, Vicki.

In: Journal of Surgical Research, Vol. 111, No. 2, 15.05.2003, p. 222-228.

Research output: Contribution to journalArticle

Johnson, Anita T. ; Kaufmann, Yihong Cao ; Luo, Shaoke ; Todorova, Valentina ; Klimberg, Vicki. / Effect of glutamine on glutathione, IGF-I, and TGF-β1. In: Journal of Surgical Research. 2003 ; Vol. 111, No. 2. pp. 222-228.
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abstract = "Background. Our previous results have showed that oral glutamine (GLN) supplementation decreased carcinogenesis in 7,12-dimethylbenz[a]antracene (DMBA) breast cancer model. We also have found that GLN raises blood glutathione (GSH) levels in an implantable breast cancer model. The process of tumor growth was accompanied by depressed GSH production and increased levels of insulin-like growth factor-I (IGF-I) and transforming growth factor β1 (TGF-β1). GSH is counter-regulatory to IGF-I. We therefore hypothesized that in DMBA model of breast cancer, the increased GSH levels seen with oral GLN would be associated with lowered levels of IGF-I &TGF-β1. Methods. Time-dated pubertal Sprague-Dawley rats were gavaged at time 0 with 1 g/kg/day glutamine (GLN) (n = 18), isonitrogenous Freamine (FA) (n = 18), or water (H2O) (n = 18). Rats were further randomized on day 7 to 100 mg/kg DMBA or oil. After 14 days, the animals were sacrificed and blood GSH, IGF-1, TGF-β1, breast tissue, and gut mucosa GSH levels were measured. Results. Oral GLN increased significantly blood, breast tissue, and gut mucosa levels of GSH in both DMBA and control groups in comparison with the control groups not treated with GLN. At the same time, the levels of blood IGF-I and TGF-β1 decreased significantly in both DMBA-treated and control groups. DMBA did not significantly affect any of these levels. Conclusions. Oral GLN increased GSH levels and lowered IGF-I and TGF-β1 in a range that is considered clinically significant. However, the effect of GLN in maintaining normal gut GSH production in the presence of DMBA was much more significant. Inconsistent with our hypothesis, reduction in IGF and TGF-β1 levels did not correlate with DMBA's effect on gut GSH production.",
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