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Indian Journal of Medical and Paediatric Oncology
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Year : 2012  |  Volume : 33  |  Issue : 1  |  Page : 13-20  

Glutamine: A novel approach to chemotherapy-induced toxicity

1 Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
3 Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Web Publication6-Jun-2012

Correspondence Address:
Manoj Pandey
Head, Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221 005, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-5851.96962

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Treatment of cancer is associated with short- and long-term side-effects. Cancer produces a state of glutamine deficiency, which is further aggravated by toxic effects of chemotherapeutic agents leading to increased tolerance of tumor to chemotherapy as well as reduced tolerance of normal tissues to the side-effects of chemotherapy. This article reviews the possible role of glutamine supplementation in reducing the serious adverse events in patients treated with anticancer drugs. The literature related to the possible role of glutamine in humans with cancer and the supportive evidence from animal studies was reviewed. Searches were made and the literature was retrieved using PUBMED, MEDLINE, COCHRANE LIBRARY, CENAHL and EMBASE, with a greater emphasis on the recent advances and clinical trials. Glutamine supplementation was found to protect against radiation-induced mucositis, anthracycline-induced cardiotoxicity and paclitaxel-related myalgias/arthralgias. Glutamine may prevent neurotoxicity of paclitaxel, cisplatin, oxaplatin bortezomib and lenolidamide, and is beneficial in the reduction of the dose-limiting gastrointestinal toxic effects of irinotecan and 5-FU-induced mucositis and stomatitis. Dietary glutamine reduces the severity of the immunosuppressive effect induced by methotrexate and improves the immune status of rats recovering from chemotherapy. In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. Current data supports the usefulness of glutamine supplementation in reducing complications of chemotherapy; however, paucity of clinical trials weakens the clear interpretation of these findings.

Keywords: Cancer, chemotherapy, glutamine, toxicity

How to cite this article:
Gaurav K, Goel R K, Shukla M, Pandey M. Glutamine: A novel approach to chemotherapy-induced toxicity. Indian J Med Paediatr Oncol 2012;33:13-20

How to cite this URL:
Gaurav K, Goel R K, Shukla M, Pandey M. Glutamine: A novel approach to chemotherapy-induced toxicity. Indian J Med Paediatr Oncol [serial online] 2012 [cited 2020 Dec 4];33:13-20. Available from: https://www.ijmpo.org/text.asp?2012/33/1/13/96962

  Introduction Top

Glutamine is a non-essential branched-chain amino acid. It is an important non-toxic nitrogen carrier in the body and an essential component of diet, especially dairy products, fish and green leafy vegetables. It participates in a variety of physiological functions, and is a major fuel source of enterocytes and is a substrate for gluconeogenesis in the kidney, lymphocytes and monocytes. It is also a nutrient in muscle protein metabolism in response to infection, inflammation and muscle trauma. [1] Because of glutamine's importance as a nitrogen carrier and respiratory fuel for enterocytes of the gut and other rapidly proliferating cells, including lymphocytes and fibroblasts, glutamine can be considered as a conditionally essential amino acid. [2] Although there are no known drug interactions with glutamine, physiological antagonism may occur with lactulose when given to treat high ammonia levels in liver failures. In some patients, glutamate may lead to brain excitation, and in patients with seizure, may make the drug less effective.

  Biochemistry Top

Glutamine is a major component of tissue of the skeletal muscle, which is the main site for the synthesis and storage of L-glutamine. When the supply of glutamine in plasma is inadequate to meet the demand, glutamine synthesis occurs in skeletal muscle and liver. Glutamine is transported to the neurons and, by the enzyme glutaminase (GA), is converted to glutamate - the potential excitotoxin. L-glutamine accounts for 30-35% of the amino acid nitrogen in the plasma. It contains two ammonia groups, one from its precursor, glutamate, and the other from free ammonia in the bloodstream. Glutamine plays an important role to prevent fluctuations in the levels of ammonia in blood by acting as a "nitrogen shuttle." It does so by acting as a buffer, accepting and then releasing excess ammonia when needed to form other amino acids, amino sugars, nucleotides and urea. This capacity to accept and donate nitrogen makes glutamine the major vehicle for nitrogen transfer among tissues. Glutamine is one of the three amino acids involved in glutathione (GSH) synthesis. GSH, an important intracellular antioxidant and hepatic detoxifier, is comprised of glutamic acid, cysteine and glycine. [3],[4] Glutamine is one of the most important substrates for ammoniagenesis in the gut and the kidney due to its important role in the regulation of acid-base homeostasis. [5] It decomposes readily to yield ammonia and glutamate or via intramolecular catalysis to pyroglutamate. Deamidation of glutamine via GA produces glutamate, a precursor of gamma-amino butyric acid. The transfer of the amide nitrogen from glutamine via the amido transferase reaction is involved in the biosynthesis of purines and pyrimidines and in the production of hexosamines. Glutamine via glutamate is converted to α-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant GSH and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for the synthesis of collagen and connective tissue [Figure 1]. However, excess glutamine in a protein is of pathological importance, and a number of neurodegenerative diseases have been found to be due to a CAG expansion that causes expansion of glutamine repeats in affected proteins (CAA and CAG codons are responsible for the insertion of glutamine from its transfer RNA with its anti-codon triplet into the genetically determined position of the coded polypeptide chain). This leads to abnormal protein folding [6] and neuronal diseases. [7]
Figure 1: Metabolism of glutamine

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Glutamine is involved in many metabolic processes in the body. Glutamine is converted to glucose when more glucose is required by the body as an energy source. Glutamine also plays a part in maintaining proper blood glucose levels and the right pH range. It is also used by white blood cells and is important for immune function. Glutamine assists in maintaining the proper acid/alkaline balance in the body, and is the basis of the building blocks for the synthesis of RNA and deoxyribonucleic acid (DNA). Glutamine regulates the expression of certain genes, including those that govern certain protective enzymes, and helps regulate the biosynthesis of DNA and RNA. Construction of DNA is dependent on adequate amounts of glutamine. It also increases the body's ability to secrete human growth hormone, which assists in metabolizing body fat and helps to support new muscle tissue growth. The glutamic acid-glutamine interconversion is of central importance to the regulation of the levels of toxic ammonia in the body, and thus among all the amino acids of blood plasma, glutamine has the highest concentration.

  Glutamine Metabolism Top

In healthy animals, the small intestine is the principal site of dietary glutamine uptake, whereas skeletal muscle and lung can be major export sites. In sepsis, the liver becomes the major organ of glutamine uptake. Following endotoxin administration [8] or starvation, [9] uptake can increase by up to 10-fold. In septic states, increased glutamine in the liver is mediated by tumor necrosis factor-alfa, glucocorticoids and prostaglandins. [10] In skeletal muscle, glutamine synthetase (GS) expression and activity increases greatly whereas no change in GA activity is observed during sepsis. Despite an increase in GS expression and activity, the rate of release exceeds that of synthesis, resulting in intracellular glutamine pool depletion. [11] If skeletal muscle is the major glutamine exporter, the high flow of blood through the pulmonary circulation and the presence of GS make the lungs a site for glutamine metabolism. [12] The GS gene expression is induced during sepsis. [13] Lymphocytes and macrophages are also great glutamine consumers, while in an inflammatory state, glutamine utilization is 10-fold greater in proliferating lymphocytes than in resting cells. [14] In the bowel, decreased glutamine utilization during sepsis occurs in the mucosal cells rather than in lymphatic tissue, [15] and reduced intestinal uptake of circulating glutamine has been observed during interleukin-1 (IL-1) treatment. [16] The maintenance of blood acid-base balance is essential for survival. Thus, increased renal ammoniagenesis and gluconeogenesis from plasma glutamine constitute an adaptative response that restores in part the acid-base balance during metabolic acidosis. [17] Renal catabolism of glutamine is acutely activated in response to the onset of metabolic acidosis and is primarily due to increased glutamine plasma and cellular decrease of glutamate and alfa-ketoglutarate (α-KG). During normal acid-base balance, approximately two-thirds of the ammonium ions produced from glutamine are trapped in the tubular lumen and excreted in acidified urine. Acute activation of the Na+ / H + exchanger acidifies the fluid in the tubular lumen and facilitates the trapping and excretion of ammonium ions. Changes in renal glutamine metabolism after endotoxin administration suggest that, during sepsis, early renal failure and altered glutamine metabolism may impair the kidney's ability to maintain acid/base homeostasis. [18] In humans, it has been shown that insulin, glucagons and epinephrine affect glutamine metabolism. [19] The gluconeogenesis from glutamine occurs principally in the kidney, whereas alanine conversion is essentially limited to the liver. [20] Renal gluconeogenesis contributes to 20-25% of whole body glucose production. [21] Overall, glutamine gluconeogenesis is responsible for about 5% of systemic glucose, and renal production of glucose from glutamine accounts for nearly 75% of all glucose derived from glutamine. Thus, it seems that glutamine is a significant contributor to whole body glucose homeostasis, while glutamate is not.

  Therapeutic Roles Top

Glutamine is one of the most common plasma amino acids, and its concentration often decreases post-operatively, [22],[23] during sepsis [24] and after multiple trauma [25] or major burns, [26] similar to a fall in the concentrations of many other amino acids, electrolytes, minerals and trace elements; therefore, it seems prudent to give glutamine supplementation in all these conditions. [27]

  Bone Marrow Transplant Top

Bone marrow transplant (BMT) is a sophisticated procedure consisting of the administration of high-dose chemoradiotherapy followed by intravenous infusion of hemopoietic stem cells to re-establish marrow function when the bone marrow is damaged or defective. BMT is used in the treatment of solid tumors, hematological diseases and autoimmune disorders. Glutamine has protein-anabolic effects and has shown a clear reduction of complications in patients undergoing BMT who exhibit post-transplant body protein wasting, gut mucosal injury leading to mucositis of gastrointestinal tract, acute graft versus host disease and immunodeficiency. Studies indicate that enteral and parenteral glutamine supplementation is well tolerated and potentially efficacious after high-dose chemotherapy or BMT for cancer treatment. Although not all studies demonstrate benefits, sufficient data has been published to suggest that this nutrient should be considered as adjunctive metabolic support of some individuals undergoing marrow transplant. [28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39] However, BMT is a rapidly evolving clinical procedure with regard to the conditioning and supportive protocols used. Thus, additional randomized, double-blind, controlled clinical trials are indicated to define the efficacy of glutamine with current BMT regimens. [28]

  Glutamine Supplementation in Chemotherapy Top

The results of glutamine supplementation and oncology in animals and humans are conflicting, [40] In vitro studies reveal an increase in cellular growth with glutamine supplementation. [41] While in vivo studies show the opposite effect, i.e. reduction in tumor growth. [42],[43] Glutamine uptake in patients with colon cancer, regardless of tumor size and cell type, is comparable to uptake in patients with healthy intestinal tissue, [44],[45] also enteral diet containing glutamine increase muscle glutamine in rats by 60% without increasing tumor growth or tumor glutamine use. [46] Glutamine supplementation in rats receiving methotrexate chemotherapy causes reduction in methotrexate-induced side-effects, including mucositis, and improved survival is observed. [47] Mucosal ulceration in rats subjected to abdominal radiation is also prevented. [48]

Growth of tumor leads to reactive increases in nucleotide and protein synthesis. High rates of protein synthesis in rapidly dividing tumors increase the demand for both essential and non-essential amino acids. [49] This demand is met by assimilating not only the nitrogen from diet but also the nitrogen from host proteins, raising the concept of tumors as "nitrogen traps," actively competing with the host for nitrogen compounds. [50] Tumors use the incorporated amino acids for both oxidation and protein synthesis. [51] Because glutamine is the main vehicle for circulation of ammonia in a non-toxic form, [52] some authors consider that tumors indeed behave as "glutamine traps." [53],[54] The highly tumorigenic human breast cancer TSE cell line exhibits up-regulation of glutamine synthetase protein and mRNA levels and a decline in intracellular glutamine content on chronic glutamine deprivation. [55]

Tumors elicit a specific response in the host nitrogen metabolism, i.e. to mobilize and augment circulating glutamine. [56],[57],[58],[59] There is a net flux of glutamine from host to tumor, which is possibly due to a net production of glutamine by host tissues as a result of an increase in the GS/GA ratio. As a rule, malignant cells transport glutamine across their plasma membranes at a faster rate than their non-malignant counterparts. [54],[60],[61]

There is increasing evidence supporting a protective role for glutamine supplementation in enteral or total parenteral nutrition. [62] In relation to cancer, it seems that a supplementation of glutamine in the diet may be beneficial for several reasons. Tumor progression has been found to be associated with an avid consumption of host glutamine by tumor cells and a depression in the activity of natural killer cells due to a decrease in GSH concentrations in these cells. Therefore, dietary supplementation of glutamine could have the beneficial effect of restoring the levels of GSH inside natural killer cells. At the same time, it could have the deleterious effect of feeding the tumor. However, because glutamine consumption by tumors is almost absolutely dissipative, an increase in the growth rate of the tumor due to this process should not be expected. [63],[64] The experimental data indicate that a dietary supplement diminishes tumor growth by restoring the function of natural killer cells and improves protein metabolism of the host or patient. [65],[66] Additionally, an oral supplement of glutamine can increase the selectivity of antitumor drugs [67],[68],[69] by protecting the patient from oxidative damage through an increase in GSH contents. [70] Several groups have shown that glutamine can also protect against oxidative damage induced by radiotherapy. [66],[69],[70]

  Glutamine and Cancer Top

Numerous studies on glutamine metabolism in cancer indicate that many tumors are avid glutamine consumers in vivo and in vitro. As a consequence of progressive tumor growth, host glutamine depletion develops and becomes a hallmark. This glutamine depletion occurs in part because the tumor behaves as a "glutamine trap" and also because of cytokine-mediated alterations in glutamine metabolism in host tissues. Animal and human studies that have investigated the use of glutamine-supplemented nutrition in the host with cancer suggest that pharmacologic doses of dietary glutamine may be beneficial. Understanding the control of glutamine metabolism in the tumor-bearing host not only improves the knowledge of metabolic regulation in the patient with cancer but also leads to improved nutritional support regimens targeted to benefit the host.

  Glutamine: Role in Increasing Selectivity of Chemotherapeutic Agents Top

Chemotherapy doses are limited by toxicity to normal tissues. Intravenous glutamine protects liver cells from oxidant injury by increasing intracellular GSH content. [71],[72] The effects of oral glutamine on tumor and host GSH metabolism and response to methotrexate (MTX) have been studied in rat models of sarcoma as well as in human patients with inflammatory breast cancer. Feeding the glutamine-enriched diets to rats receiving MTX decreases tumor GSH while increasing or maintaining host GSH stores. [73],[74],[75] Diminished GSH levels in tumor cells increases susceptibility to chemotherapy. Significantly decreased GSH content in tumor cells in the glutamine-supplemented group correlates with enhanced tumor volume loss. [76] These data suggest that oral glutamine supplementation will enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to radiation-induced and chemotherapy treatment-related injury. [77],[76]

  Effect of Glutamine on Methotrexate Efficacy and Toxicity Top

Oral glutamine has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. Studies in both laboratory rats and in breast cancer indicate a three-fold increase in total MTX in the tumor in the glutamine receiving group as compared with the control group, and this increase was in both the diglutamated and in the pentaglutamated MTX. There was also a significant decrease in the total polyglutamated MTX in the gut in the glutamine group. In a phase I trial, patients diagnosed with inflammatory breast cancer received glutamine during MTX neoadjuvant therapy in escalating doses for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral glutamine was detected. No patient showed any sign of chemotherapy-related toxicity and all patients responded to the chemotherapy regimen, suggesting that glutamine supplementation is safe and may augment the response of MTX-based regimens. Thus, glutamine by selectively increasing tumor retention of MTX compared with normal host tissue increases the therapeutic window of chemotherapeutic drugs. [75] Experimental evidence indicates a very good correlation between the activity of mitochondrial GA and the rate of respiration of tumor mitochondria in the presence of glutamine. [78]

  Role of Glutamine in Metabolism-Dependent Toxicity of Cyclophosphamide Top

Studies have shown that acrolein produced during the metabolism of cyclophosphamide (CP) binds to proteins and, by doing so, may denature these proteins and acrolein in vivo, preferentially reacting with GSH and sulfhydryl-containing compounds, and may protect against acrolein toxicity and at the same time not interfere with the chemotherapeutic activity of CP. [79] The main source of this GSH is glutamine. Besides CP, GSH is also extremely effective in trapping metabolites of acetaminophen, phenacetin and bromobenzene and in preventing their covalent binding to protein both in vivo and in vitro.

  Oral Glutamine in the Prevention of Fluorouracil-Induced Intestinal Toxicity Top

5-Fluorouracil (FU) in association with folinic acid (FA) is the most frequently used chemotherapeutic agent in colorectal cancer, but it often causes diarrhea. Animal and human studies suggest that glutamine stimulates intestinal mucosal growth. A double-blind randomized trial with placebo and oral glutamine has shown that glutamine reduces changes in intestinal absorption and permeability (assessed by d-xylose urinary excretion and cellobiose-mannitol test, respectively) induced by FU and may have a protective effect on the FU-induced diarrhea. [80] Although there is no evidence of a beneficial effect of glutamine during pelvic radiotherapy-induced diarrhea for colonic carcinoma [81] a beneficial effect of oral glutamine for FU-induced diarrhea in colonic carcinoma is supported. [82] Even mild diarrhea must not be discounted when evaluating the effect of chemotherapy-induced diarrhea. Thus, careful monitoring, early identification and aggressive management must be applied to all grades of diarrhea. [83] There is also some evidence showing that glutamine and alanine-glutamine have trophic effects not only in the ileum but also in the proximal and distal colon. This could be important during parenteral nutrition, when mucosal atrophy may weaken the gut barrier. [84]

  Oral Glutamine to Prevent Chemotherapy-Induced Stomatitis Top

Mucositis is a common toxicity of cancer chemotherapy. Glutamine appears to be the major energy source for intestinal epithelium, and animal studies have suggested that dietary supplementation with glutamine may protect the gut from both radiation and chemotherapy. Experimental studies have shown that oral supplementation with glutamine can significantly decrease the severity of chemotherapy-induced stomatitis, an important cause of morbidity in the treatment of patients with cancer, [85],[86] although the dose given and duration of therapy varies widely upon pathological conditions. [87] Other modalities of prevention of chemotherapy-induced mucositis, like oral cooling, granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor and laser, are available, none of them have uniform efficacy. [88] Studies in mice suggest that alanyl-glutamine, not glutamine, speeds intestinal recovery when compared in 5-FU-treated mice, predominantly by enhancing mitotic activity and crypt length. [89] To evaluate the effect of therapeutic interventions in patients with chemotherapy-induced mucositis, testing intestinal permeability via the measurement of [51] Cr-EDTA urinary excretion after oral challenge may be useful as shown in some experiments. [90],[91]

  Glutamine and Protection Against Anthracycline-Induced Cardiotoxicity Top

Glutamine supplementation maintained cardiac GSH levels in animal models given methotrexate or CP. In rat models given lethal and sublethal doses of CP, glutamine­supplemented rats were observed to have much less cardiotoxicity and had improved survival rates compared with those who were not supplemented, possibly through the upregulation of cardiac GSH. [92],[93]

High-dose doxorubicin therapy causes both acute and, more commonly, chronic cardiac toxicity, which manifests as dose-related cardiomyopathy due to doxorubicin-induced free radicals. Oxidative damage due to doxorubicin-induced free radical results in decreased GSH and depletes superoxide dysmutase in cardiac muscle. [94],[95],[96] These molecules alter DNA, causing mitochondrial dysfunction, eliciting a cellular calcium overload, causing acute depression of GSH levels and inducing the release of catecholamine. [97],[98]

The incidence of cardiac toxicity can be reduced by using a weekly schedule of doxorubicin rather than every 21 days (lower peak drug levels), or by the use of dexrazoxane, a derivative of EDTA. [98] This agent may enhance mucositis and myelosuppression during treatment, and also has been reported in one study to alter antitumor efficacy. [99] Mechanisms by which glutamine plays a protective role in the myocardial cell is through upregulation of GSH and, secondly, induction of heat shock protein (HSP). HSP 72 is known to be protective to the myocardium against hypoxic/ischemic injury. Induction of HSP 27 (another protective heat shock protein) has been shown to be protective against doxorubicin-induced cardiac injury. [100] Glutamine also appears to be a potent inducer of myocardial HSP 72 in an in vivo rat model. [101] Several trials are being conducted presently to prove the possible role of glutamine protection via HSP 72/27 induction in the heart. In addition, recent evidence indicate that glutamine can preserve myocardial high-energy phosphate levels and prevent accumulation of lactate following a variety of stress, including infection and ischemia/reperfusion injury. [102],[103]

  Glutamine as a Neuroprotective Agent in Taxane and other Neurotoxic Therapy Top

Glutamine has been proposed as a potentially neuroprotective agent in patients receiving paclitaxel. In one non-randomized study, neurological signs and symptoms and changes in nerve-conduction studied in 46 consecutive patients receiving high-dose paclitaxel either with or without glutamine was assessed. Patients who received glutamine developed significantly less weakness, less loss of vibratory sensation and less toe numbness than controls. The percent change in the compound motor action potential and sensory nerve action potential amplitudes after paclitaxel treatment was lower in the glutamine group, but this finding was not statistically significant in these small groups. [104]

Another clinical trial evaluating the role of glutamine taken orally in the prevention of neurotoxicity among 86 patients with colorectal cancer who were being treated with Eloxatin, a common agent causing neurotoxicity, showed a significantly lower incidence of peripheral neuropathy compared with controls. [105]

  Glycyl-Glutamine-Dipeptide in the Parenteral Nutrition of Patients with Acute Leukemia Undergoing Intensive Chemotherapy Top

The effects of parenteral glycyl-glutamine supplementation in patients with acute leukemia receiving intensive conventional chemotherapy was evaluated in a randomized, double-blind, controlled study that compared a standard glutamine-free parenteral nutrition with a glycyl-glutamine-supplemented parenteral nutrition containing 20 g of glutamine. There was significant faster neutrophil recovery in the group that received glutamine supplementation along with high-dose cytarabine chemotherapy as compared with those patients receiving cytarabine regimen alone. There was no significant difference in the recovery of CD4+ or CD8+ lymphocytes or monocyte activation between the two groups. The authors concluded that there is a possible role of glutamine in the stimulation of lymphocyte proliferation. [106]

  Conclusions Top

The influence of glutamine on body homeostasis is protean. States of physiologic stress, including those resulting from the treatment of malignant disease, are characterized by a relative deficiency of glutamine. Supplementation with this inexpensive dietary supplement may have an important role in the prevention of gastrointestinal, neurologic and, possibly, cardiac complications of cancer therapy. These complications often negatively affect the quality of life and may also lead to changes in therapy, which potentially alter efficacy. Glutamine may also improve the therapeutic index of both chemotherapy and radiation, increasing cytotoxicity while concurrently protecting against toxicity. However, the current evidence is not sufficient to recommend its regular use. Further studies of glutamine supplementation in these areas is warranted and multicentric, placebo-controlled phase III studies are needed to evaluate the role of glutamine for the prevention of mucositis, neurotoxicity and cardiotoxicity, and for the prevention of hepatic venoocclusive disease in patients undergoing hematopoietic cell transplantation before any definitive recommendation can be made.

  References Top

1.Bergstrom J, Furst P, Norée LO, Vinnars E. Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol 1974;36:693-7.  Back to cited text no. 1
2.Lacey J, Wilmore D. Is glutamine a conditionally essential amino acid? Nutr Rev 1990;48:297-309.  Back to cited text no. 2
3.Souba WW. Glutamine Physiology, Biochemistry, and Nutrition in Critical Illness. Austin, TX: R.G. Landes Co.; 1992.  Back to cited text no. 3
4.Askanazi J, Carpentier YA, Michelsen CB, Elwyn DH, Furst P, Kantrowitz LR, et al. Muscle and plasma amino acids following injury: Influence of intercurrent infection. Ann Surg 1980;192:78-85.  Back to cited text no. 4
5.Halperin HL, Kamel HS, Ethier JH. Biochemistry and physiology of ammonium excretion. In: Seldin DW, Giebisch L, editors. The kidney: Physiology and pathology. New York: Raven Press; 1992. p. 2645-80.  Back to cited text no. 5
6.Satyal SH, Schmidt E, Kitagawa K, Sondheimer N, Lindquist S, Kramer JM, et al. Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc Natl Acad Sci USA 2000;97:5750-5.  Back to cited text no. 6
7.Carmichael J, Chatellier J, Woolfson A, Milstein C, Fersht AR, Rubinsztein DC. Bacterial and yeast chaperones reduce both aggregate formation and cell death in mammalian cell models of Huntington's disease. Proc Natl Acad Sci USA 2000;97:9701-5.  Back to cited text no. 7
8.Inoue Y, Pacitti AJ, Souba WW. Endotoxin increases hepatic glutamine transport activity. J Surg Res 1993;54:393-400.  Back to cited text no. 8
9.Fischer CP, Bode BP, Souba WW. Starvation and endotoxin act independently and synergistically to coordinate hepatic glutamine transport. J Trauma 1996;40:688-92.  Back to cited text no. 9
10.Inoue Y, Bode BP, Souba WW. Antibody to TNF-alpha blocks LPS-stimulated hepatic amino acid transport. Surgery 1994;116:356-65.  Back to cited text no. 10
11.Austgen TR, Chakrabarti R, Chen MK, Souba WW. Adaptive regulation in skeletal muscle glutamine metabolism in endotoxintreated rats. J Trauma 1992;32:600-6.  Back to cited text no. 11
12.Welbourne TC. Interorgan glutamine flow in metabolic acidosis. Am J Physiol 1987;253: F1069-76.  Back to cited text no. 12
13.Lukaszewicz G, Abcouwer SF, Labow BI, Souba WW. Glutamine synthetase gene expression in the lungs of endotoxin-treated and adrenalectomized rats. Am J Physiol 1997;273:L1182-90.  Back to cited text no. 13
14.Brand K, Leibold W, Luppa P, Schoerner C, Schulz A. Metabolic alterations associated with proliferation of mitogen activated lymphocytes and of lymphoblastoid cell lines: Evaluation of glucose and glutamine metabolism. Immunobiology 1986;73:23-34.  Back to cited text no. 14
15.Souba WW, Herskowitz K, Klimberg VS, Salloum RM, Plumley DA, Flynn TC, et al. The effects of sepsis and endotoxemia on gut glutamine metabolism. Ann Surg 1990;211:543-9.  Back to cited text no. 15
16.Austgen TR, Chen MK, Dudrick PS, Copeland EM, Souba WW. Cytokine regulation of intestinal glutamine utilization. Am J Surg 1991;163:174-9.  Back to cited text no. 16
17.Brosnan JT, Vinay P, Gougoux A, Halperin ML. Renal ammonia production and its implications for acid base balance. In: Häussinger D, editor. PH homeostasis-mechanism and control. New York, NY: Academic Press 1988; p. 281-304.  Back to cited text no. 17
18.Austgen TR, Chen MK, Moore W, Souba WW. Endotoxin and renal glutamine metabolism. Arch Surg 1991;126:23-7.  Back to cited text no. 18
19.Gerich JE, Meyer C, Stumvoll MW. Hormonal control of renal and systemic glutamine metabolism. J Nutr 2000;130:995S-1001S.  Back to cited text no. 19
20.Stumvoll M, Meyer C, Perriello G, Kreider M, Welle S, Gerich J. Human kidney and liver gluconeogenesis evidence for organ substrate selectivity. Am J Physiol 1998;274: E817-26.  Back to cited text no. 20
21.Stumvoll M, Perriello G, Meyer C, Gerich J. Role of glutamine in human carbohydrate metabolism in kidney and other tissues. Kidney Int 1999;55:778-92.  Back to cited text no. 21
22.Blomqvist BI, Hammarqvist F, von der Decken A, Wernerman J. Glutamine and alpha-ketoglutarate prevent the decrease in muscle free glutamine concentration and influence protein synthesis after total hip replacement. Metabolism 1995;44:1215-22.  Back to cited text no. 22
23.Parry-Billings M, Baigrie RJ, Lamont PM, Morris PJ, Newsholme EA. Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg 1992;127:1237-40.  Back to cited text no. 23
24.Planas M, Schwartz S, Arbós MA, Farriol M. Plasma glutamine levels in septic patients. J Parenter Enteral Nutr 1993;17:299-300.  Back to cited text no. 24
25.Wernerman J, Hammarkvist F, Ali MR, Vinnars E. Glutamine and ornithine-alpha-ketoglutarate but not branched-chain amino acids reduce the loss of muscle glutamine after surgical trauma. Metabolism 1989;38:63-6.  Back to cited text no. 25
26.Parry-Billings M, Evans J, Calder PC, Newsholme EA. Does glutamine contribute to immunosuppression after major burns? Lancet 1990;336:523-5.  Back to cited text no. 26
27.Ziegler TR. Glutamine and Acute Illness. Br J Nutr 2002;87(Suppl 1):S9-15.  Back to cited text no. 27
28.Muscaritoli M, Grieco G, Capria S, Iori AP, Rossi Fanelli F. Nutritional and metabolic support in patients undergoing bone marrow transplantation. Am J Clin Nutr 2002;75:183-90.  Back to cited text no. 28
29.Brown SA, Goringe A, Fegan C, Davies SV, Giddings J, Whittaker JA, et al. Parenteral glutamine protects hepatic function during bone marrow transplantation. Bone Marrow Transplant 1998;22:281-4.  Back to cited text no. 29
30.Goringe AP, Brown S, O'Callaghan U, Rees J, Jebb S, Elia M, et al. Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy. Bone Marrow Transplant 1998;22:2879-84.  Back to cited text no. 30
31.Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation: A randomized, double blind, controlled study. Ann Intern Med 1992;116:821-8.  Back to cited text no. 31
32.Jebb SA, Marcus R, Elia M. Oral Glutamine Supplementation in patients receiving bone marrow transplantation. Clin Nutr 1995;14:162-5.  Back to cited text no. 32
33.Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy induced stomatitis: A pilot study. J Lab Clin Med 1996;127:223-8.  Back to cited text no. 33
34.Wilmore DW, Schloerb PR, Ziegler TR. Glutamine in the support of patients following bone marrow transplantation. Curr Opin Clin Nutr Metab Care 1999;2:323-7.  Back to cited text no. 34
35.MacBurney M, Young LS, Ziegler TR, Wilmore DW. A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. J Am Diet Assoc 1994;94:1263-6.  Back to cited text no. 35
36.Anderson PM, Ramsay NK, Shu XO, Rydholm N, Rogosheske J, Nicklow R, et al. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant 1998;22:339-44.  Back to cited text no. 36
37.Coghlin Dickson TM, Wong RM, Offrin RS, Shizuru JA, Johnston LJ, Hu WW, et al. Effect of oral glutamine supplementation during bone marrow transplantation. J Parenter Enteral Nutr 2000;24:61-6.  Back to cited text no. 37
38.Schloerb PR, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications: A randomized, double-blind study. J Parenter Enteral Nutr 1993;17:407-13.  Back to cited text no. 38
39.Van Zaanen HC, van der Lelie H, Timmer JG, Fürst P, Sauerwein HP. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 1994;74:2879-84.  Back to cited text no. 39
40.Miller AL. Therapeutic considerations of L-glutamine: A review of the literature. Alternat Med Rev 1999;4:239-48.  Back to cited text no. 40
41.Kang YJ, Feng Y, Hatcher EL. Glutathione stimulates A549 cell proliferation in glutamine-deficient culture: The effect of glutamine supplementation. J Cell Physiol 1994;161:589-96.  Back to cited text no. 41
42.Bartlett DL, Charland S, Torosian MH. Effect of glutamine on tumor and host growth. Ann Surg Oncol 1995;2:71-6.  Back to cited text no. 42
43.Fahr MJ, Kornbluth J, Blossom S, Schaeffer R, Klimberg VS. Glutamine enhances immunoregulation of tumor growth. JPEN J Parenter Enteral Nutr 1994;18:471-6.  Back to cited text no. 43
44.Souba WW, Strebel FR, Bull JM, Copeland EM, Teagtmeyer H, Cleary K. Interorgan glutamine metabolism in the tumor-bearing rat. J Surg Res 1988;44:720-6.  Back to cited text no. 44
45.van der Hulst RR, von Meyenfeldt MF, Deutz NE, Soeters PB. Glutamine extraction by the gut is reduced in depleted patients with gastrointestinal cancer. Ann Surg 1997;225:112-21.  Back to cited text no. 45
46.Klimberg VS, Souba WW, Dolson DJ, Salloum RM, Hautamaki RD, Plumley DA, et al. Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 1990;66:62-8.  Back to cited text no. 46
47.Fox AD, Kripke SA, De Paula J, Berman JM, Settle RG, Rombeau JL. Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis. JPEN J Parenter Enteral Nutr 1988;12:325-31.  Back to cited text no. 47
48.Klimberg VS, Souba WW, Salloum RM, Plumley DA, Cohen FS, Dolson DJ, et al. Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. J Surg Res 1990;48:319-23.  Back to cited text no. 48
49.Medina MA, Núñez de Castro I. Evidence of an intracellular dissipative structure. Z Naturforsch C 1988;43:793-4.  Back to cited text no. 49
50.Landel AM, Hammond WG, Meguid MM. Aspects of amino acid and protein metabolism in cancer-bearing states. Cancer 1985;55:230-7.  Back to cited text no. 50
51.Shapot VS. On the multiform relationships between the tumor and the host. Adv Cancer Res 1979;30:89-150.  Back to cited text no. 51
52.Medina MA, Sánchez-Jiménez F, Márquez J, Rodríguez Quesada A, Núñez de Castro I. Relevance of glutamine metabolism to tumor cell growth. Mol Cell Biochem 1992;113:1-15.  Back to cited text no. 52
53.Klimberg VS, McClellan JL. Glutamine, cancer, and its therapy. Am J Surg 1996;172:418-24.  Back to cited text no. 53
54.Souba WW. Glutamine and cancer. Ann Surg 1993;218:715-28.  Back to cited text no. 54
55.Collins CL, Wasa M, Souba WW, Abcouwer SF. Regulation of glutamine synthetase in human breast carcinoma cells and experimental tumors. Surgery 1997;122:451-63.  Back to cited text no. 55
56.Carrascosa JM, Martínez P, Núñez de Castro I. Nitrogen movement between host and tumor in mice inoculated with Ehrlich ascitic tumor cells. Cancer Res 1984;44:3831-5.  Back to cited text no. 56
57.Márquez J, Núñez de Castro I. Mouse liver free amino acids during the development of Ehrlich ascites tumour. Cancer Lett 1991;58:221-4.  Back to cited text no. 57
58.Quesada AR, Medina MA, Márquez J, Sánchez-Jiménez FM, Núñez de Castro I. Contribution by host tissues to circulating glutamine in mice inoculated with Ehrlich ascites tumor cells. Cancer Res 1988;48:1551-3.  Back to cited text no. 58
59.Quesada AR, Medina MA, Núñez de Castro I. Mobilization of glutamine and asparagine in mouse kidney during Ehrlich cell carcinoma development. Cancer Lett 1996;105:29-32.  Back to cited text no. 59
60.Espat NJ, Bode BP, Lind DS, Copeland EM, Souba WW. Normalization of tumor-induced increases in hepatic amino acid transport after surgical resection. Ann Surg 1995;221:50-8.  Back to cited text no. 60
61.Medina MA, Quesada AR, Núñez de Castro I. L-Glutamine transport in native vesicles isolated from Ehrlich ascites tumor cell membranes. J Bioenerg Biomembr 1991;23:689-97.  Back to cited text no. 61
62.Amores-Sánchez MI, Medina MA. Glutamine as a precursor of glutathione, and oxidative stress. Mol Genet Metab 1999;67:100-5.  Back to cited text no. 62
63.Austgen TR, Dudrick PS, Sitren H, Bland KI, Copeland E, Souba WW. The effects of glutamine-enriched total parenteral nutrition on tumor growth and host tissues. Ann Surg 1992;215:107-13.  Back to cited text no. 63
64.Medina MA, Núñez de Castro I. Glutaminolysis and glycolysis interactions in proliferant cells. Int J Biochem 1990;22:681-3.  Back to cited text no. 64
65.Fahr MJ, Kornbluth J, Blossom S, Schaeffer R, Klimberg VS. Glutamine enhances immunoregulation of tumor growth. J Parenter Enteral Nutr 1994;18:471-6.  Back to cited text no. 65
66.Yoshida S, Kaibara A, Yamsaki K, Ishibashi N, Noake T, Kakegawa T. Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats. J Parenter Enteral Nutr 1995;19:492-7.  Back to cited text no. 66
67.Cao Y, Kennedy R, Klimberg VS. Glutamine protects against doxorubicin-induced cardiotoxicity. J Surg Res 1999;85:178-82.  Back to cited text no. 67
68.Decker-Baumann C, Buhl K, Frohmuller S, von Herbay A, Dueck M, Schlag PM. Reduction of chemotherapy-induced side effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer. Eur J Cancer 1999;35:202-7.  Back to cited text no. 68
69.Miller AL. Therapeutic considerations of L-glutamine: A review of the literature. Altern Med Rev 1999;4:239-48.  Back to cited text no. 69
70.Klimberg VS, Nwokedi E, Hutchins LF, Pappas AA, Lang NP, Broadwater JR, et al. Glutamine facilitates chemotherapy while reducing toxicity. JPEN J Parenter Enteral Nutr 1992;16(6 suppl):83S-7S.  Back to cited text no. 70
71.Smith CV, Mitchell JR. Pharmacological aspects of glutathione in drug metabolism. In: Dolphin D, Poulson R, Avramovic O, editors. Coenzymes and Cofactors. New York: John Wiley and Sons; 1989. p. 1-44.  Back to cited text no. 71
72.Glutathione: Chemical biochemical and medical aspects. Part B. New York: John Wiley and Sons; 1989. p. 1-44.  Back to cited text no. 72
73.Nirenberg A, Mosende C, Mehta BM, Gisolfi AL, Rosen G. High-dose methotrexate concentrations and corrective measures to avert toxicity. Cancer Treat Rep 1977;61:779-83.  Back to cited text no. 73
74.Chan H, Evans WE, Pratt CB. Recovery from toxicity associated with high-dose methotrexate: Prognostic factors. Cancer Treat Rep 1977;61:797-801.  Back to cited text no. 74
75.Rubio IT, Cao Y, Hutchins LF, Westbrook KC, Klimberg VS. Effect of Glutamine on Methotrexate Efficacy and Toxicity. Ann Surg 1998;227:772-80.  Back to cited text no. 75
76.Jensen JC, Nwokedi E, Baker ML, Bevans DW 3 rd , Baker ML, Pappas AA, et al. Prevention of chronic radiation enteropathy by dietary glutamine. Ann Surg Oncol 1994;1:157-63.  Back to cited text no. 76
77.Rouse K, Nwokedi E, Woodliff JE, Epstein J, Klimberg VS. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg 1995;221:420-6.  Back to cited text no. 77
78.Kovacevic Z, Morris HP. The role of glutamine in the oxidative metabolism of malignant cells. Cancer Res 1972;32:326-33.  Back to cited text no. 78
79.Gurtoo HL, Hipkens JH, Sharma SD. Role of glutathione in the metabolism-dependent toxicity and chemotherapy of cyclophosphamide. Cancer Res 1981;41:3584-91.  Back to cited text no. 79
80.Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity a double blind, placebo controlled, randomized trial. Gut 2001;48:28-33.  Back to cited text no. 80
81.Kozelsky TF, Meyers GE, Sloan JA. Shanahan TG, Dick SJ, Moore RL. Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol 2003;21:1669-74.  Back to cited text no. 81
82.Ziegler TR. Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. J Nutr 2001;131:2578S-84S.  Back to cited text no. 82
83.Richardson G, Dobish R. Chemotherapy induced diarrhea. J Oncol Pharm Pract 2007;13:181.  Back to cited text no. 83
84.Scheppach W, Loges C, Bartram P, Christl SU, Richter F, Dusel G, et al. Effect of free glutamine and alanyl-glutamine dipeptide on mucosal proliferation of the human ileum and colon. Gastroenterol 1994;107:429-34.  Back to cited text no. 84
85.Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy induced stomatitis: A pilot study. J Lab Clin Med 1996;127:223-8.  Back to cited text no. 85
86.Cerchietti LC, Navigante AH, Lutteral MA, Castro MA, Kirchuk R, Bonomi M, et al. Double-blinded, placebo-controlled trial on intravenous l-alanyl-l-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006;65:1330-7.  Back to cited text no. 86
87.García-de-Lorenzo A, Zarazaga A, García-Luna PP, Gonzalez-Huix F, López-Martínez J, Miján A, et al. Clinical evidence for enteral nutritional support with glutamine: A systematic review. Nutrition 2003;19:805-11.  Back to cited text no. 87
88.Plevovà P. Prevention and treatment of chemotherapy- and radiotherapy-induced oral mucositis: A review. Oral Oncol 1999;35:453-70.  Back to cited text no. 88
89.Carneiro-Filho BA, Oriá RB, Wood Rea K, Brito GA, Fujii J, Obrig T, et al. Alanyl-glutamine hastens morphologic recovery from 5-fluorouracil-induced mucositis in mice. Nutrition 2004;20:934-41.  Back to cited text no. 89
90.Melichar B, Kohout P, Brátová M, Solichová D, Králícková P, Zadák Z. Intestinal permeability in patients with chemotherapy-induced stomatitis. J Cancer Res Clin Oncol 2001;127:314-8.  Back to cited text no. 90
91.Choi K, Lee SS, Oh SJ, Lim SY, Lim SY, Jeon WK, et al. The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr 2007;26:57-62.  Back to cited text no. 91
92.Vanderpool D, Klimberg V. Oral glutamine protects against cyclophosamide induced cardiotoxicity and death through changes in glutathione metabolism (abstract). Assoc Acad Surg 1993.  Back to cited text no. 92
93.Cao Y, Kennedy R, Klimberg V. Glutamine protects against doxorubicin-induced cardiotoxicity. J Surg Res 1999;85:178-82.  Back to cited text no. 93
94.Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by n-acetylcysteine. J Clin Invest 1981;68:1053-64.  Back to cited text no. 94
95.Olson RD, Boerth RC, Gerber JG, Nies AS. Mechanism of adriamycin cardiotoxicity: Evidence for oxidative stress. Life Sci 1981;29:1393-401.  Back to cited text no. 95
96.Julicher R, Sterrenberg L, Bast A, Riksen RO, Koomen JM, Noordhoek J. The role of lipid peroxidation in acute doxorubicin-induced cardiotoxicity as studied in rat isolated heart. J Pharm Pharmacol 1986;38:277-82.  Back to cited text no. 96
97.Kennedy R, Wyeth R, Seifen E, Liu S, Fontenot HJ, Seifen E. Effects of doxorubicin on cardiac contractility, glutathione and lipid peroxidation. FASEB J 1996;10: A169.  Back to cited text no. 97
98.Curran C, Narang P, Reynolds R. Toxicity profile of dexrazoxane (Zinecard, ICRF-187, ADR-529, NSC-169780): A modulator of doxorubicin cardiotoxicity. Cancer Treat Rev 1991;18:241-52.  Back to cited text no. 98
99.Speyer J, Green M, Kramer E, Rey M, Sanger J, Ward C, et al. Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer. N Engl J Med 1988;319:745-52.  Back to cited text no. 99
100.Strauss M, Anselmi G, Hermoso T, Tejero F. Carnitine promotes heat shock protein synthesis in adriamycin-induced cardiomyopathy in a neonatal rat experimental model. J Mol Cell Cardiol 1998;30:2319-25.  Back to cited text no. 100
101.Wischmeyer P, Kahana M, Wolfson R, Ren H, Musch MM, Chang EB. Glutamine induces heat shock protein and protects against endotoxin shock in the rat. J Appl Physiol 2001;90 : 2403-10.  Back to cited text no. 101
102.Wischmeyer P, Singleton K, Serkova N. Glutamine preserves ATP levels and decreases tissue lactate in the myocardium following sublethal endotoxin shock. Shock 2002;17S:58.  Back to cited text no. 102
103.Wischmeyer P, Jayakar D, Williams U, Singleton KD, Riehm J, Bacha EA, et al. Single dose of glutamine preserves myocardial tissue metabolism, glutathione content, and enhances myocardial function following ischemia-reperfusion injury. J Parenter Enteral Nutr 2003;27:396-403.  Back to cited text no. 103
104.Stubblefield MD, Vahdat LT, Balmaceda CM, Troxel AB, Hesdorffer CS, Gooch CL. Glutamine as a neuroprotective agent in high-dose: Paclitaxel-induced peripheral neuropathy. Clin Oncol 2005;17:271-6.  Back to cited text no. 104
105.Wang WS, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, et al. Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist 2007;12:312-9.  Back to cited text no. 105
106.Scheid C, Hermann K, Kremer G, Holsing A, Heck G, Fuchs M, et al. Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy . Nutrition 2004;20:249-54.  Back to cited text no. 106


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