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Glutamine therapy of cancers (2/4)
Glutamine as an immunomodulator
Over the last 10 years studied was the role of glutamine as an immunomodulator. Observations of patients suggest that supplementation Glutamine reduces tumor growth include also by stimulation of immune (3).
Lymphocytes are a type of rapidly dividing cells, which glutamine in operation as a priority fuel. Glutamine is an important
component of the lymphocytes to divide in culture in vitro (outside the organism in a test tube). Other amino acids or combinations of glutamate and ammonia can not replace glutamine. NK (Natural Killers)
They are cytotoxic lymphocytes capable of killing cancer cells, as well as produce cytokines essential in the fight against cancer. Tumors do not grow well in patients with high activity of NK cells. Optimal the functioning of lymphocytes (including NK) cells is dependent on adequate supply of glutamine and glutathione. Studies have documented an increase
NK cell activity in patients supported with glutamine (10,11).
Klimberg et al. observed a correlation between tumor growth,
NK cell activity, prostaglandin synthesis and concentration of PGE2
glutathione in the breast cancer model in rats. Equal numbers of rats with
inbred Fisher 344, were added to the feed glutamine or
the same in terms of nitrogen content, the amount of free amines. After seven
weeks after tumor implantation, animals were examined. Group
supplemented with glutamine had increased activity of NK cells,
increased glutathione levels, decreased levels of PGE2 and a smaller volume
tumor compared to the supplemented free amines. Group
supplemented with free amines showed a 40% greater tumor volume,
increased levels of PGE2, reduced glutathione levels, lower activity
NK cells and the presence of metastases (12).
The authors conclude that oral administration of glutamine resulted in
slower tumor growth by increasing the activity of NK cells, which
was supported by the inhibition of PGE2 and by glutathione.
Shewchuk et al. also showed reduced tumor weight in organisms
Glutamine supplementation in hepatic tumor model. They suggest that
inhibition of tumor may be more dependent on NK cell activity
and improved immune response (13).
Glutamine and radiotherapy
Poradiacyjne colitis is an important clinical problem
patients treated with ionizing radiation in the abdominal area, and
pelvis. Intestinal mucosal damage caused by irradiation of
areas of cell damage is scripted, reduced height
intestinal villi, ulceration and necrosis of the intestinal epithelium (15).
These patients suffer from abdominal pain, bloody diarrhea, impaired
absorption and in some cases, bacterial dysbiozy (16).
Severe cases may be complicated by strictures, constipation,
bowel perforations and fistulas.
The role of glutamine as a preferred fuel for the gastrointestinal tract
is well documented (17-19). Studies on glutamine are
designed to protect against, as well as treatment after radiotherapy.
It appears that glutamine reveals its positive effect on three different
roads (20).
1. as the primary fuel for enterocytes,
2. as a precursor for the synthesis of nucleotides necessary for regeneration
cells
3. as a source of glutathione - a strong antioxidant.
Previous studies Souby et al. documented reduced
incidence of bacterial dysbiosis glutamine supplementation in rats and
areas of abdominal irradiation. Four days after irradiation were investigated
in these animals peritoneal lymph nodes. In rats that received
dose of radiation without glutamine supplementation were found in 89%
intestinal dysbiosis, while in the group supplemented with glutamine -
only 20%. In colorectal control groups that received
diet with or without glutamine, dysbiozy found in 0% and 12% (21).
Yoshida et al. found that oral glutamine supplementation reduced the
leakage from the intestinal epithelium in patients with advanced cancer
esophagus treated with chemoradiation (22). It follows that
exogenous glutamine maintains / retains intestinal barrier by
reduce the appearance of the mucosa, and increased number and height
intestinal villi (23).
Jenson et al. studied the effect of glutamine on the late or chronic
poradiacyjne damage. Studying rats found that the earlier
Glutamine supplementation prevented the chronic damage
poradiacyjnym intestines. Chronic condition in this study were defined
as two months after irradiation. The degree of damage in a group
glutamine supplementation almost did not deviate from the results in the group not
irradiated (24).
Klimberg et al. found a beneficial effect of oral glutamine on
morphology of intestinal mucosa cells and tolerance to radiotherapy
both in the administration of prophylactic and post-irradiation as
Recovery factor (25).
Oral glutamine supply administered prior to irradiation seems to
exert a protective effect by improving the intestinal metabolism
seen as an increase in intestinal epithelial cells and
increase in their height, as well as overall improvement in cell proliferation.
Glutamine abused during or after irradiation reduces the degree of
damage and accelerates the healing irradiated intestine, both by
improve the structure of cells and improve the metabolism of glutamine
gut (3). The same researchers in further studies showed that
glutamine administration may increase the sensitivity of cells
ionizing radiation. In an animal model was observed by 65%
greater reduction in tumor cells in animals treated with
Glutamine and irradiated as compared to the control group, in which
glutamine was not given.
Literature Cited:
9) Ardawi, MSM, et al, Maximum Activities of some Enzymes of
glycolysis, the TCA cycle, ketone body and glutamine utilization
pathways in lymphocytes of the rat. Biochem J 208:743-8,1982
10) Juretic A, et al, Glutamine Requirements in the generation of LAK
cells. Clin Nutr 13:42, 1994
11) Liang C, et al, Glutathione regulates IL-2 activity on cytotoxic
T-cells. J Biol Chem. 264 (23): 13579, 1989
12) Klimberg VS et al, Glutamine suppresses PGE2 synthesis and breast
cancer growth. J Surg Res 63:293-7. 1996
13) Shewchuck LD et al, Dietary L-glutamine supplementation reduces
The growth of the Morris hepatoma 7777 in Exercise-Trained and
sedentary rats. J Nutr 127:158-66,1997
14) Bartlett DL, Effect of glutamine on tumor and host growth. Ann
Surg Oncol 2:71-6,1995
15) Berthrong M, Pathological changes secondary to radiation, World J
Surg 10:155-170,1986
16) Guzman G, et al, Abdominal radiation bacterial Causes
translocation, J Surg Res 46:104-107, 1989
17) Souba W et al, Glutamine metabolism in the intestinal tract
: Invited review, JPEN 9:608-617,1985
18) HG Windmueller, Glutamine utilization by the small intestine, Adv.
Enzymol 53:201-237, 1982
19) VS Klimberg, Glutamine: A key factor in Establishing and
Maintaining intestinal health. Symposium Proceedings, October 1990
20) VS Klimberg, Glutamine protects How the gut During irradiation,
ICCN, 3:21, 1996
21) Souba W et al, Oral glutamine reduces bacterial translocation
Following abdominal radiation, J Surg Res 48:1-5,1990
22) Yoshida S et al, Effects of glutamine supplements and
radiochemotherapy on systemic immune and gut barrier function in
Patients with advanced esophageal cancer, Ann Surg 227:485-491,1998
23) VS Klimberg, Oral glutamine accelerates healing of the small
intestine and improves outcome after whole abdominal radiation, Arch
Surg 125:1040-1045,1990
24) Jensen J et al, Dietary Glutamine prevents chronic radiation
enteropathy, Ann Surg Oncol 1:157-163,1993
25) Klimberg VS et al, Prophylactic glutamine protects the intestinal
mucosa from radiation injury, Cancer 1:62-68,1990
tbc ...
MD Piotr Krzysztof Michalak
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