Prevention of chemotheraphy and radiation toxicity with glutamine

Cancer Treatment Reviews

Volumn 29, Issue 6, 2003, Pages 501-513

  Savarese, Diane M F ^a,e   Savy, Gayle ^b   Vahdat, Linda ^c   Wischmeyer, Paul E ^d   Corey, Barbara ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b Corpak Medsystems ^*  (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

^d UNIVERSITY OF COLORADO   (United States)

^e NONE   (United States)

Author keywords

Cancer; Chemoprotectant; Chemotherapy; Glutamine; Radiation

Indexed keywords

7 ETHYL 10 HYDROXYCAMPTOTHECIN; ANTHRACYCLINE; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; CARBOPLATIN; CISPLATIN; DIPHENOXYLATE; DOXIFLURIDINE; DOXORUBICIN; ETOPOSIDE; FLUOROURACIL; FOLINIC ACID; GLUTAMINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IFOSFAMIDE; IRINOTECAN; LOPERAMIDE; METHOTREXATE DERIVATIVE; OPIATE; PACLITAXEL; RAZOXANE; SUCRALFATE; TAXANE DERIVATIVE; THALIDOMIDE; VINCRISTINE; GLUTATHIONE;

ANTINEOPLASTIC ACTIVITY; BONE MARROW SUPPRESSION; CANCER; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER RADIOTHERAPY; CARDIOMYOPATHY; CARDIOTOXICITY; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; DIARRHEA; DISEASE EXACERBATION; DISEASE SEVERITY; DRUG FORMULATION; DRUG INDUCED DISEASE; DRUG INHIBITION; DRUG MEGADOSE; DRUG METABOLISM; ENTEROCOLITIS; EVIDENCE BASED MEDICINE; HUMAN; INCIDENCE; LIVER VENOOCCLUSIVE DISEASE; MEDICAL LITERATURE; MEDLINE; MOTOR NEUROPATHY; MUCOSA INFLAMMATION; MYALGIA; NEUROTOXICITY; NONHUMAN; PUBLICATION; RADIATION INJURY; REVIEW; SENSITIZATION; CHEMICALLY INDUCED DISORDER; DIET SUPPLEMENTATION; DIGESTIVE SYSTEM; HEART DISEASE; METABOLISM; NEOPLASM;

ANTHRACYCLINES; ANTINEOPLASTIC AGENTS; DIETARY SUPPLEMENTS; DIGESTIVE SYSTEM; GLUTAMINE; GLUTATHIONE; HEART DISEASES; HUMANS; NEOPLASMS; PACLITAXEL; RADIATION INJURIES;

EID: 0242475358     PISSN: 03057372     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0305-7372(03)00133-6     Document Type: Review

References (130)

1. Bergstrom J, Furst P, Noree L, et al. Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol 1974; 36: 693-697.
2. Lacey J, Wilmore D. Is glutamine a conditionally essential amino acid? Nutr Rev 1990; 48: 297-309.
3. Bartlett D, Charland S, Torosian M. Effect of glutamine on tumor and host growth. Ann Surg Oncol 1995; 2: 71-76.
4. Klimberg V, Souba W, Salloum R. Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. J Surg Res 1990; 48: 319-323.
5. Van Der Hulst R, Kreel B, Von Meyenfeldt M, et al. Glutamine and the preservation of gut integrity. Lancet 1993; 341: 1363-1365.
6. Shewchuk L, Baracos V, Field C. Dietary L-glutamine supplementation reduces the growth of the morris hepatoma 7777 in exercise-trained and sedentary rats. J Nutr 1997; 127: 158-166.
7. Ardawi M, Newsholme E. Glutamine metabolism in lymphocytes of the rat. Biochem J 1983; 212: 835-842.
8. Souba W, Smith R, Wilmore D. Glutamine metabolism by the intestinal tract. JPEN 1985; 9: 608-617.
9. Klimberg V, Souba W, Dolson D, et al. Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 1990; 66: 62-68.
10. Souba W, Wilmore D. Gut-liver interaction during accelerated gluconeogenesis. Arch Surg 1985; 120: 66-70.
11. Souba W, Wilmore DS. Postoperative alteration of arteriovenous exchange of amino acids across the gastrointestinal tract. Surgery 1983: 342-350.
12. Kapadia C, Muhlbacher F, Smith R, et al. Alterations in glutamine metabolism in response to operative stress and food deprivation. Surg Forum 1982; 33: 19-21.
13. Vente J, Von Meyenfeldt M, Van Eijk H, et al. Plasma amino acid profiles in sepsis and stress. Ann Surg 1989; 209: 57-62.
14. Furst P, Albers S, Stehle P. Evidence for a nutritional need for glutamine in catabolic patients. Kidney Int 1989; 36: S287-S292.
15. Cao Y, Feng Z, Hoos A, et al. Glutamine enhances gut glutathione production. JPEN 1998; 22: 224-227.
16. Welbourne T. Ammonia production and glutamine incorporation into glutathione in the functioning rat kidney. Can J Biochem 1979; 57: 233-237.
17. Godwin A, Meister A, O'Dwyer P, et al. High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis. Proc Natl Acad Sci USA 1992; 89: 3070.
18. Arrick B, Nathan C. GSH metabolism as a determinant of therapeutic efficacy: a review. Cancer Res 1984; 44: 4224-4232.
19. Wolf C, Lewis A, Carmichael J, et al. The role of glutathione in determining the response of normal and tumor cells to anticancer drugs. Biochem Soc Trans 1987; 15: 728-730.
20. Hong R, Rounds J, William S, et al. Glutamine preserves liver glutathione after lethal hepatic injury. Ann Surg 1992; 215: 114-119.
21. Rouse K, Nwokedi E, Woodliff J, et al. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg 1995; 221: 420-426.
22. Klimberg V, Nwokedi B, Hutchins L, et al. Does glutamine facilitate chemotherapy while reducing its toxicity? Surg Forum 1991; 42: 16-18.
23. Klimberg V, Pappas A, Nwokedi E, et al. Effect of supplemental dietary glutamine on methotrexate concentrations in tumors. Arch Surg 1992; 127: 1317-1320.
24. Carretero J, Obrador E, Pellicer J, Pascual A, Estrela J. Mitochondrial glutathione depletion by glutamine in growing tumor cells. Free Radic Biol Med 2000; 29: 913-923.
25. Wolf C, Hayward I, Lawrie S, et al. Cisplatinum-sensitive and resistant ovarian adenocarcinoma cell lines derived from the same patient (abstract). Proc Am Assoc Cancer Res 1985; 26: 338.
26. Ziegler T, Benfell K, Smith R, et al. Safety and metabolic effects of L-glutamine administration in humans. JPEN 1990; 14: 137S-146S.
27. Windmueller H. Glutamine utilization by the small intestine. Adv Enzymol 1982; 53: 201-237.
28. Panigrahi P, Gewolb I, Bamford P, et al. Role of glutamine in bacterial transcytosis and epithelial cell injury. JPEN 1997; 21: 75-80.
29. Kouznetsova L, Bijlsma P, van Leeuwen P, et al. Glutamine reduces phorbol-12,13-dibutyrate-induced macromolecular hyperpermeability in HT-29Cl.19A intestinal cells. JPEN 1999; 23: 136-139.
30. Hall J, Heel K, McCauley R. Glutamine. Br J Surg 1996; 83: 305-312.
31. Klimberg V, et al. Glutamine, cancer, and its therapy. Am J Surg 1996; 172: 418-424.
32. Weber FJ, Veach G. The importance of the small intestine in gut ammonium production in the fasting dog. Gastroenterology 1979; 77: 235-240.
33. Chance W, Cao Y, Kim M, et al. Reduction of tumor growth following treatment with a glutamine antimetabolite. Life Sci 1988; 42: 87-94.
34. Chen M, Austgen T, Klimberg V, et al. Tumor glutamine use exceeds intestinal glutamine use in cachectic tumor-bearing rats. Surg Forum 1990; 41: 12-14.
35. Chen M, Salloum R, Austgen T, et al. Tumor regulation of hepatic glutamine metabolism. JPEN 1991; 15: 159-164.
36. Fahr M, Kornbluth J, Blossom S, et al. Glutamine enhances immunoregulation of tumor growth. JPEN 1994; 18: 471-476.
37. Liang C, Lee N, Cattell D, et al. Glutathione regulates interleukin-2 activity on cytotoxic T-cells. J Biol Chem 1989; 264: 13519-13523.
38. Erickson R, Ross D, Medina J. Effects of glutamine on head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 1999; 121: 348-354.
39. Lin C, Abcouwer S, Souba W. Effect of dietary glutamate on chemotherapy-induced immunosuppression. Nutrition 1999; 15: 687-696.
40. Liu S, Shi D, Shen Z, Wu Y. Effects of glutamine on tumor growth and apoptosis of hepatoma cells. Acta Pharmacol Sin 2000; 21: 668-672.
41. Do T, Vahdat L, Fine R, Petrylak D. Lack of inhibitory effect of glutamine on the cytotoxicity of taxanes in human breast and prostate cancer cells. In: Proceedings of the AACR-NCI-EORTC International Conference. Molecular targets and cancer therapeutics: discovery, biology, and clinical applications, Miami Beach, FL, 2001. p. 30a.
42. Juretic A, Spagnoli G, Horig H, et al. Glutamine requirements in the generation of lymphokine-activated killer cells. Clin Nutr 1994; 13: 42-49.
43. Klimberg V, Kornbluth J, Cao Y, et al. Glutamine suppresses PGE2 synthesis and breast cancer growth. J Surg Res 1996; 63: 293-297.
44. Gismondo M, Drago L, Fassina M, et al. Immunostimulating effect of oral glutamine. Dig Dis Sci 1998; 43: 1752-1754.
45. Bjarnason I, Macpherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology 1995; 108: 1566-1581.
46. Li J, Langkamp-Henken B, Suzuki K, et al. Glutamine prevents parenteral nutrition-induced increases in intestinal permeability. JPEN 1994; 18: 303-307.
47. Ziegler T, Young L, Benfel K, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. Ann Int Med 1992; 116: 821-828.
48. Rhoads J, Keku E, Quinn J, et al. L-Glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis. Gastroenterology 1991; 100: 683-691.
49. Wischmeyer P. Glutamine and heat shock protein expression. Nutrition 2002; 18: 225-228.
50. Wischmeyer P, Musch M, Madonna M, et al. Glutamine protects intestinal epithelial cells: role of inducible HSP 70. Am J Physiol 1997; 272: G879-G884.
51. Musch M, Hayden D, Sugi K, et al. Cell-specific induction of HSP72-mediated protection by glutamine against oxidant injury in IEC18 cells (abstract). Proc Assoc Am Phys 1998; 110: 136-139.
52. Wischmeyer P, Kahana M, Wolfson R, et al. Glutamine induces heat shock protein and protects against endotoxin shock in the rat. J Appl Physiol 2001; 90: 2403-2410.
53. Berthrong M. Pathologic changes secondary to radiation. World J Surg 1986; 10: 155-170.
54. Guzman-Stein G, Bonsack M, Liberty J, et al. Abdominal radiation causes bacterial translocation. J Surg Res 1989; 46: 104-107.
55. Klimberg V. How glutamine protects the gut during irradiation. J Crit Care Nutr 1996; 3: 21-25.
56. Jensen J, Schaefer R, Nwokedi E, et al. Prevention of chronic radiation enteropathy by dietary glutamine. Ann Surg Oncol 1994; 1: 157-163.
57. Souba W, et al. Oral glutamine reduces bacterial translocation following abdominal radiation. J Surg Res 1990; 48: 1-5.
58. Kozelsky T, Meyers G, Sloan J, et al. 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: 1669-1674.
59. Huang E, Leung S, Wang C, et al. Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys 2000; 46: 535-540.
60. Rombeau J. A review of the effects of glutamine-enriched diets on experimentally induced enterocolitis. JPEN 1990; 14: 100S-105S.
61. Fox A, Kripke S, DePaula J, et al. Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis. JPEN 1988; 12: 325-331.
62. Rubio I, Cao Y, Hutchins L, et al. Effect of glutamine on methotrexate efficacy and toxicity. Ann Surg 1998; 227: 772-780.
63. Mahood D, Dose A, Loprinzi C, et al. Inhibition of fluorouracil-induced stomatitis by oral cryotherapy. J Clin Oncol 1991; 9: 449-452.
64. Rocke L, Loprinzi C, Lee J, et al. A randomized clinical trial of two different durations of oral cryotherapy for prevention of 5-fluorouracil-related stomatitis. Cancer 1993; 72: 2234-2238.
65. Cascinu S, Fedeli A, Fedeli S, et al. Control of chemotherapy-induced diarrhea with octreotide. Oncology 1994; 51: 70-73.
66. Gabrilove J, Jakubowski A, Scher H, et al. Effect of granulocyte colony stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional cell carcinoma of the urothelium. N Engl J Med 1988; 318: 1414-1422.
67. Chi K, Chen C, Chan W, et al. Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol 1995; 13: 2620-2628.
68. Hejna M, Kostler W, Raderer M, et al. Decrease of duration and symptoms in chemotherapy-induced oral mucositis by topical GM-CSF: results of a prospective randomised trial. Eur J Cancer 2001; 37: 1994-2002.
69. van Zaanen H, van der Lelie H, Timmer J, et al. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 1994; 74: 2879-2884.
70. Schloerb P, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study). JPEN 1993; 17: 407-413.
71. Decker-Baumann C, Buhl K, Frohmuller S, et al. Reduction of chemotherapy-induced side-effects by parental glutamine supplementation in patients with metastatic colerectal cancer. Eur J Cancer 1999; 35: 202-207.
72. Skubitz K, Anderson P. Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med 1996; 127: 223-228.
73. Okuno S, Woodhouse C, Loprinzi C, et al. Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy. Am J Clin Oncol 1999; 22: 258-261.
74. Anderson P, Schroeder G, Skubitz K. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998; 83: 1433-1439.
75. Jebb S, Osborne R, Maughan T, et al. 5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation. Br J Cancer 1994; 70: 732-735.
76. Selby P, Lopes N, Mundy J, et al. Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy. Br J Cancer 1987: 531-533.
77. Grem J, Shoemaker DD, Petrelli NJ, et al. Severe and fatal toxic effects observed in treatment with high and low-dose leucovorin plus 5-fluorouracil for colorectal carcinoma. Cancer Treat Rep 1987; 71: 1122.
78. Lewis J. Gastrointestinal injury due to medicinal agents. Am J Gastroenterol 1986; 81: 819-834.
79. Wadler S, Benson A, Engelking C. Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol 1998; 16: 3169-3178.
80. Muscaritoli M, Micozzi A, Conversano L, et al. Oral glutamine in the prevention of chemotherapy-induced gastrointestinal toxicity. Eur J Cancer 1997; 33.
81. Bozzetti F, Biganzoli L, Gavazzi C. Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition 1997; 13: 748-751.
82. Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut 2001; 48: 28-33.
83. Rougier P, Bugat R, Douillard J, et al. Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and pretreated with fluorouracil-based chemotherapy. J Clin Oncol 1997; 15: 251-260.
84. Rothenberg M, Cox J, DeVore R, et al. A multicenter, Phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma. Cancer 1999; 85: 786-795.
85. Rothenberg M, Eckardt J, Kuhn J, et al. Phase II trial of irinotecan in patients with progressive or rapidly recurrent colorectal cancer. J Clin Oncol 1996; 14: 1128-1135.
86. Saliba F, Hagipantelli R, Misset J. Pathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer. J Clin Oncol 1998; 16: 2745-2751.
87. Hecht J. Gastrointestinal toxicity of irinotecan. Oncology 1998; 12: 72-78.
88. Pitot H, Wender D, O'Connell M, et al. Phase II trial of irinotecan in patients with metastatic colorectal carcinom. J Clin Oncol 1997; 15: 2910-2919.
89. Abigerges D, Armand J. Irinotecan (CPT) high-dose escalation using intensive high-dose loperamide to control diarrhea. J Natl Cancer Inst 1994; 86: 446-449.
90. Conti J, Kemeny N, Saltz L, et al. Irinotecan is an active agent in untreated patients with metastatic colorectal cancer. J Clin Oncol 1996; 14: 709-715.
91. Rhoads J, Keku E, Bennett L, et al. Development of L-glutamine-stimulated electroneural sodium absorption in piglet jeunum. Am J Physiol 1990; 259: 99-107.
92. Savarese D, Al-Zoubi A, Boucher J. Glutamine for irinotecan diarrhea (letter). J Clin Oncol 2000; 18: 450-451.
93. Govindarajan R, Heaton K, Broadwater R, Zeitlin A, et al. Effect of thalidomide on gastrointestinal toxic effects of irinotecan. Lancet 2000; 356: 566-567.
94. Murray S, Pindoria S. Nutrition support for bone marrow transplant patients (Cochrane Review). In: The Cochrane Library. Update Software: Oxford, 2002.
95. Cockerham M, Weinberger B, Lerchie SB. Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother 2000; 34: 300-303.
96. Anderson P, Ramsay N, Shu X, et al. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant 1998; 22: 339-344.
97. Canovas G, Leon-Sanz M, Gomez P, Valero M, Gomis P, La Huerta J. Oral glutamine supplements in autologous hematopoietic transplant: impact on gastro-intestinal toxicity and plasma protein levels. Haematologica 2000; 85: 1229-1230.
98. Coghlin Dickson T, Wong R, Offrin R, et al. Effect of oral glutamine supplementation during marrow transplantation. JPEN J Parent Enteral Nutr 2000; 24: 61-66.
99. Pironi L, Paganelli G, Miglioli M, et al. Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection. JPEN 1994; 18: 351-354.
100. Hwang T, O'Dwyer S, Smith R, et al. Preservation of small bowel mucosa using glutamine-enriched parenteral nutrition. Surg Forum 1986; 37: 56-58.
101. Brown S, Goringe A, Fegan C, et al. Parenteral glutamine protects hepatic function during bone marrow transplantation. Bone Marrow Transplant 1998; 22: 281-284.
102. Schloerb P, Skikne B. Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study. JPEN 1999; 23: 117-122.
103. Scrobohaci M, Drouet L, Monem-Mansi A, et al. Liver veno-occlusive disease after bone marrow transplantation changes in coagulation parameters and endothelial markers. Thromb Res 1991; 63: 509.
104. Bearman S. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood 1995; 85: 3005-3020.
105. Schiff P, Faut J, Horowitz S. Promotion of microtubule assembly in-vitro by Taxol. Nature 1979; 277: 665-667.
106. Horowitz S, Lothstein L, Manfredi J, et al. Taxol: mechanism of action and resistance. Ann N Y Acad Sci 1986; 466: 733-744.
107. Schwartz J. Axonal transport: components, mechanisms, and specificity. Annu Rev Neurosci 1979; 2: 467-504.
108. Smalheiser N. Cell attachment and neurite stability in NG 108-15 cells: what is the role of microtubules? Dev Brain Res 1991; 58: 271-272.
109. Freilich R, Balmaceda C, Seidman A, et al. Motor neuropathy due to docetaxel and paclitaxel. Neurology 1996; 47: 115-118.
110. Apfel S. Managing the neurotoxicity of paclitaxel (Taxol) and docetaxel (Taxotere) with neurotrophic factors. Cancer Invest 2000; 18: 564-573.
111. Sikov W, Akerley W, Strenger R, Cummings F. Weekly high-dose paclitaxel demonstrates significant activity in advanced breast cancer (abstract). Proc Am Soc Clin Oncol 1998; 17: 112a.
112. Akerley W, Herndon J, Egorin M, Lyss A, et al. Weekly, high-dose paclitaxel in advanced lung carcinoma: a Phase II study with pharmacokinetics by the Cancer and Leukemia Group B. Cancer 2003; 97: 2480-2486.
113. Boyle F, Wheeler H, Shenfield G. Amelioration of experimental cisplatin and paclitaxel neuropathy with glutamate. J Neurooncol 1999; 41: 107-116.
114. Boyle F, Wheeler H, Shenfield G. Glutamate ameliorates experimental vincristine neuropathy. J Pharm Exp Ther 1996; 279: 410-415.
115. Vahdat L, Papadopoulos K, Lange D, et al. Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res 2001; 7: 1192-1197.
116. Savarese D, Boucher J, Corey B. Glutamine treatment of paclitaxel-induced myalgias and arthralgias (letter). J Clin Oncol 1998; 16: 3918-3919.
117. Jacobson S, Loprinzi C, Sloan J, et al. Glutamine for preventing paclitaxel-associated myalgias and arthralgias: unfortunately a "no go" (abstract). Proc Am Soc Clin Oncol 2002; 21: 366a.
118. DeSantis S, Pace A, Bove L, et al. Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor. Clin Cancer Res 2000; 6: 90-95.
119. Apfel S, Lipton R, Arezzo J, et al. Nerve growth factor prevents toxic neuropathy in mice. Ann Neurol 1991; 29: 87-90.
120. Vanderpool D, Klimberg V. Oral glutamine protects against cyclophosamide induced cardiotoxicity and death through changes in glutathione metabolism (abstract). Association Of Academic Surgeons; 1993.
121. Doroshow J, Locker G, Ifrim I, et al. Prevention of doxorubicin cardiac toxicity in the mouse by n-acetylcysteine. J Clin Invest 1981; 68: 1053-1064.
122. Olson R, Boerth R, Gerber JG, et al. Mechanism of adriamycin cardiotoxicity: evidence for oxidative stress. Life Sci 1981; 29: 1393-1401.
123. Julicher R, Sterrenberg L, Bast A, et al. The role of lipid peroxidation in acute doxorubicin-induced cardiotoxicity as studied in rat isolated heart. J Pharm Pharmacol 1986; 38: 277-282.
124. Kennedy R, Wyeth R, Seifen E, et al. Effects of doxorubicin on cardiac contractility, glutathione and lipid peroxidation. FASEB J 1996; 10: A169.
125. 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: 241-252.
126. Speyer J, Green M, Kramer E, 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: 745-752.
127. Cao Y, Kennedy R, Klimberg V. Glutamine protects against doxorubicin-induced cardiotoxicity. J Surg Res 1999; 85: 178-182.
128. Strauss M, Anselmi G, Hermoso T, et al. Carnitine promotes heat shock protein synthesis in adriamycin-induced cardiomyopathy in a neonatal rat experimental model. J Mol Cell Cardiol 1998; 30: 2319-2325.
129. 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.
130. Wischmeyer P, Jayakar D, Williams U, et al. Single dose of glutamine preserves myocardial tissue metabolism, glutathione content, and enhances myocardial function following ischemia-reperfusion injury (abstract). Am J Clin Nutr, 2003, in press.