Gut glutathione metabolism and changes with 7,12-DMBA and glutamine

Anita T. Johnson, Yihong Kaufmann, Shaoke Luo, Kirk Babb, Roger Hawk, Vicki Klimberg

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Introduction. The mechanism by which oral glutamine (GLN) prevents 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer is unknown. While GLN triples the negative extraction of gut glutathione (GSH) in rats, DMBA significantly disrupts it. Actual gut GSH flux has not been reported. We hypothesized that the gut is a producer of GSH; DMBA blocks gut GSH production and supplemental oral GLN antagonizes this effect. Materials and methods. Eighty Sprague-Dawley rats were randomized to four groups (n = 20/group): DMBA + GLN, DMBA + FA, OIL + GLN, OIL + FA. Rats (age 50 days) were gavaged with a one-time dose of 100 mg/kg DMBA or oil. Rats were gavaged with AES-14 as GLN (1 gm/kg/day) or an isonitrogenous amount of Freamine (FA) from 1 week before till sacrifice at 1 week after DMBA (greatest effect on gut GSH extraction). Arterial and portal blood was taken for GLN and GSH levels, and blood flow was measured using 14C-PAH. Gut GLN and GSH fluxes (uptake or production) were calculated. Results. DMBA abrogated the normal GSH production (negative flux) in OIL + FA while not affecting GLN metabolism. GLN maintained GSH production in DMBA + GLN. Conclusions. Oral GLN restores to normal GSH production in DMBA-treated animals suggesting one of the mechanism(s) by which GLN prevents breast cancer in this model. Unchanged uptake of GLN in the DMBA-treated animals may indicate a block in GSH transport rather than actual intracellular production.

Original languageEnglish (US)
Pages (from-to)242-246
Number of pages5
JournalJournal of Surgical Research
Volume115
Issue number2
DOIs
StatePublished - 2003
Externally publishedYes

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Glutamine
Glutathione
Oils
anthracene
Breast Neoplasms
Sprague Dawley Rats

Keywords

  • 7,12-dimethylbenz(a)anthracene (DMBA)
  • Glutamine
  • Glutathione
  • Gut gluatathione production

ASJC Scopus subject areas

  • Surgery

Cite this

Gut glutathione metabolism and changes with 7,12-DMBA and glutamine. / Johnson, Anita T.; Kaufmann, Yihong; Luo, Shaoke; Babb, Kirk; Hawk, Roger; Klimberg, Vicki.

In: Journal of Surgical Research, Vol. 115, No. 2, 2003, p. 242-246.

Research output: Contribution to journalArticle

Johnson, Anita T. ; Kaufmann, Yihong ; Luo, Shaoke ; Babb, Kirk ; Hawk, Roger ; Klimberg, Vicki. / Gut glutathione metabolism and changes with 7,12-DMBA and glutamine. In: Journal of Surgical Research. 2003 ; Vol. 115, No. 2. pp. 242-246.
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abstract = "Introduction. The mechanism by which oral glutamine (GLN) prevents 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer is unknown. While GLN triples the negative extraction of gut glutathione (GSH) in rats, DMBA significantly disrupts it. Actual gut GSH flux has not been reported. We hypothesized that the gut is a producer of GSH; DMBA blocks gut GSH production and supplemental oral GLN antagonizes this effect. Materials and methods. Eighty Sprague-Dawley rats were randomized to four groups (n = 20/group): DMBA + GLN, DMBA + FA, OIL + GLN, OIL + FA. Rats (age 50 days) were gavaged with a one-time dose of 100 mg/kg DMBA or oil. Rats were gavaged with AES-14 as GLN (1 gm/kg/day) or an isonitrogenous amount of Freamine (FA) from 1 week before till sacrifice at 1 week after DMBA (greatest effect on gut GSH extraction). Arterial and portal blood was taken for GLN and GSH levels, and blood flow was measured using 14C-PAH. Gut GLN and GSH fluxes (uptake or production) were calculated. Results. DMBA abrogated the normal GSH production (negative flux) in OIL + FA while not affecting GLN metabolism. GLN maintained GSH production in DMBA + GLN. Conclusions. Oral GLN restores to normal GSH production in DMBA-treated animals suggesting one of the mechanism(s) by which GLN prevents breast cancer in this model. Unchanged uptake of GLN in the DMBA-treated animals may indicate a block in GSH transport rather than actual intracellular production.",
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AU - Hawk, Roger

AU - Klimberg, Vicki

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AB - Introduction. The mechanism by which oral glutamine (GLN) prevents 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer is unknown. While GLN triples the negative extraction of gut glutathione (GSH) in rats, DMBA significantly disrupts it. Actual gut GSH flux has not been reported. We hypothesized that the gut is a producer of GSH; DMBA blocks gut GSH production and supplemental oral GLN antagonizes this effect. Materials and methods. Eighty Sprague-Dawley rats were randomized to four groups (n = 20/group): DMBA + GLN, DMBA + FA, OIL + GLN, OIL + FA. Rats (age 50 days) were gavaged with a one-time dose of 100 mg/kg DMBA or oil. Rats were gavaged with AES-14 as GLN (1 gm/kg/day) or an isonitrogenous amount of Freamine (FA) from 1 week before till sacrifice at 1 week after DMBA (greatest effect on gut GSH extraction). Arterial and portal blood was taken for GLN and GSH levels, and blood flow was measured using 14C-PAH. Gut GLN and GSH fluxes (uptake or production) were calculated. Results. DMBA abrogated the normal GSH production (negative flux) in OIL + FA while not affecting GLN metabolism. GLN maintained GSH production in DMBA + GLN. Conclusions. Oral GLN restores to normal GSH production in DMBA-treated animals suggesting one of the mechanism(s) by which GLN prevents breast cancer in this model. Unchanged uptake of GLN in the DMBA-treated animals may indicate a block in GSH transport rather than actual intracellular production.

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