Glutamin ve β-hidroksi β-metil bütiratin metotreksatin indüklediği intestinal mukozit üzerine etkisi
Year 2020,
Volume: 45 Issue: 1, 266 - 271, 31.03.2020
Mehmet Alakaya
,
Elvan Çağlar Çıtak
Simge Taşkınlar
Sakir Necat Yılmaz
,
Ahmet Ata Özçimen
Mehmet Yavuz Burak Çimen
Abstract
Amaç: Metotreksatın sebep olduğu intestinal mukozit üzerinde Glutamin (Gln) ve β-hidroksi β-metilbutiratın (HMB) önleyici etkilerini değerlendirmeyi amaçladık
Gereç ve Yöntem: 50 Wistar albino cinsi sıçan 5 gruba (G) ayrıldı. G1 kontrol grubu ve G2 metotreksat (MTX) ile tedavi edilen gruptu. G3, G4 ve G5 sırasıyla MTX ve Gln, Mtx ve HMB, MTX ve Gln, HMB verilen gruplardı. Sıçanlara üç gün intraperitoneal MTX uygulandı. Beşinci günde bağırsak doku örnekleri alındı.
Bulgular: G5 kript derinlik ölçümleri G1 grubu ile benzerdi. Park skorlamasına göre G1 ve G5, beş çalışma grubu arasında en yüksek skoru alan gruplardı. Doku kaspaz-3 ile incelendiğinde, en düşük apoptotik oran G5'te bulundu.
Sonuç: Bu çalışma, Gln ve HMB kullanım kombinasyonunun her iki kimyasal maddenin ayrı kullanımından daha etkili olduğunu göstermiştir
Supporting Institution
Mersin Üniversitesi Bilimsel Araştırma Projeleri Birimi
Project Number
BAP-TF DTB (MA) 2012- 4 TU
References
- 1. Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004;100(9 Suppl):2026–2046
- 2. Pico JL, Avila-Garavito A, Naccache P. Mucositis: its occurrence, consequences, and treatment in the oncology setting. The Oncologist 1998;3: 446–451
- 3. Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004;100:1995–2025
- 4. van Zanten AR., Dhaliwal R., Garrel D., Heyland DK. Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis. Crit Care. 2015 Aug 18;19:294
- 5. Neu J, Li N. Pathophysiology of glutamine and glutamate metabolism in premature infants. Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):75-9
- 6. Sido B, Seel C, Hochlehnert A, et al. Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation? Dig Dis Sci. 2006;51:2170–9
- 7. van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet. 1993;341:1363–5
- 8. Coeffier M, Dechelotte P. The role of glutamine in intensive care unit patients: mechanisms of action and clinical outcome. Nutr Rev. 2005;63:65–9
- 9. Pimentel GD, Rosa JC, Lira FS, et al. β-Hydroxy-β-methylbutyrate (HMB) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway. Nutr Metab 2011;8:11-18
- 10. Nissen S, Sharp R, Ray M, et al. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physion 1996;81:2095-2104
- 11. Nunes EA, Kuczera D, Brito GA, et al. Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expres-sion. Nutr Res 2008;28:487-493
- 12. Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg. 2002;236:369-374
- 13. Park PO, Haglund U, Bulkley GB, et al. The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion. Surgery 1990;107:574–578
- 14. Miyazono Y, Gao F, Horie T. Oxidative stress contributes to methotrexate induced small intestinal toxicity in rats. Scand J Gastroenterol. 2004; 39: 1119-1127
- 15. Taminiau JA, Gall DG, Hamilton JR. Response of the rat small-intestine epithelium to methotrexate. Gut 1980; 21: 486-492
- 16. Gibson RJ, Keefe DM, Thompson FM, et al. Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats. Dig Dis Sci. 2002; 47: 2751–2757
- 17. Gulgun M, Erdem O, Oztas E, et al. Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress. Exp Toxicol Pathol 2010; 62: 109-115
- 18. Noé JE. L-Glutamine use in the treatment and prevention of mucositis and cachexia: a naturopathic perspective. Integr Cancer Ther. 2009 8:409–415
- 19. Miller AL. Therpeutic Considerations of L-Glutamine : A Review of the Literature Altren Med Rev 1999; 4: 239-248
- 20. Gaurav K, Goel RK, Shukla M, et al. Glutamine: A novel approach to chemotherapy-induced toxicty. Indian J Med Paediatr Oncol. 2012; 33: 13-20
- 21. Fox AD, Kripke SA, De Paula J, et al. Effect of a glutamine-suplemented enteral diet on methotrexate-induced enterocolitis. JPEN J Parenter Enteral Nutr 1988;12:325-331
- 22. Erbil Y, Oztezcan S, Giriş M, et al. The effect of glutamine on radiation-induced organ damage. Life Sci. 2005;78:376-382
- 23. Williams JZ, Abumrad N, Barbul A. Effect of a Specialized Amino Acid Mixture on Human Collagen Deposition. Ann Surg 2002;236:369-374
- 24. Peterson A, Qureshi MA, Ferket PR, et al. In vitro exposure with [beta]-hydroxy-[beta]-methylbutyrate enhances chicken macrophage growth and function. Vet Immunol Immunopathol 1999; 67:67-78
- 25. Eley HL, Russell ST, Tisdale MJ. Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by β-hydroxy-β-methylbutyrate. Am J Physiol Endocrinol Metab. 2008; 295: 1409-1416
- 26. Eley HL, Russell ST, Tisdale MJ. Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-a and angiotensin II by β-hydroxy-β- methylbutyrate. Am J Physiol Endocrinol Metab. 2008; 295: 1417-1426
- 27. Eley HL, Russell ST, Baxter JH, et al. Signaling pathways initiated by β-hydroxy-β- methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab. 2007; 293: 923-931
- 28. Manzano M, Giron MD, Salto R, et al. Is β-hydroxy-β-methylbutyrate (HMB) the bioactive metabolite of L-leucine (LEU) in muscle? Molecular evidence and potential implications. Abstract presented at: European Society for Clinical Nutrition and Metabolism 31st Congress; Vienna, Austria; 2009. Abstract P267
- 29. Sukhotnik I, Shehadeh N, Coran AG, et al. Oral insulin enhances cell proliferation and decreases enterocyte apoptosis during methotrexate-induced mucositis in the rat. J Pediatr Gastroenterol Nutr 2008;47:115-122
Effects of glutamine and β-hydroxy β-methyl butyrate on methotrexate induced intestinal mucositis
Year 2020,
Volume: 45 Issue: 1, 266 - 271, 31.03.2020
Mehmet Alakaya
,
Elvan Çağlar Çıtak
Simge Taşkınlar
Sakir Necat Yılmaz
,
Ahmet Ata Özçimen
Mehmet Yavuz Burak Çimen
Abstract
Purpose: We aimed to evaluate preventing effects of Glutamine (Gln) and β-hydroxy β-methylbutyrate (HMB) on methotrexate induced intestinal mucositis
Materials and Methods: Fifty Wistar albino rats were divided into 5 groups (G). Group G1 defined as control and G2 was the methotrexate (MTX) treated group. The group G3, G4 and G5 were MTX plus Gln, Mtx plus HMB, MTX plus Gln and HMB respectively. Distilled water was applied by gavage to the first 2 groups. Rat received intraperitoneal injections of MTX at the third day. On the fifth day intestinal tissue samples were obtained.
Results: The G5 had similar results with the G1 group in the crypt length. According to Park scoring, G1 and G5 were both the highest scores among five study groups. When the tissue was inspected by caspase-3 coating, the lowest apoptotic rate is found in the G5.
Conclusion: This research showed that the combination of Gln and HMB use is more effective then the separate use of both chemicals.
Project Number
BAP-TF DTB (MA) 2012- 4 TU
References
- 1. Rubenstein EB, Peterson DE, Schubert M, et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004;100(9 Suppl):2026–2046
- 2. Pico JL, Avila-Garavito A, Naccache P. Mucositis: its occurrence, consequences, and treatment in the oncology setting. The Oncologist 1998;3: 446–451
- 3. Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004;100:1995–2025
- 4. van Zanten AR., Dhaliwal R., Garrel D., Heyland DK. Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis. Crit Care. 2015 Aug 18;19:294
- 5. Neu J, Li N. Pathophysiology of glutamine and glutamate metabolism in premature infants. Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):75-9
- 6. Sido B, Seel C, Hochlehnert A, et al. Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation? Dig Dis Sci. 2006;51:2170–9
- 7. van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet. 1993;341:1363–5
- 8. Coeffier M, Dechelotte P. The role of glutamine in intensive care unit patients: mechanisms of action and clinical outcome. Nutr Rev. 2005;63:65–9
- 9. Pimentel GD, Rosa JC, Lira FS, et al. β-Hydroxy-β-methylbutyrate (HMB) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway. Nutr Metab 2011;8:11-18
- 10. Nissen S, Sharp R, Ray M, et al. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physion 1996;81:2095-2104
- 11. Nunes EA, Kuczera D, Brito GA, et al. Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expres-sion. Nutr Res 2008;28:487-493
- 12. Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg. 2002;236:369-374
- 13. Park PO, Haglund U, Bulkley GB, et al. The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion. Surgery 1990;107:574–578
- 14. Miyazono Y, Gao F, Horie T. Oxidative stress contributes to methotrexate induced small intestinal toxicity in rats. Scand J Gastroenterol. 2004; 39: 1119-1127
- 15. Taminiau JA, Gall DG, Hamilton JR. Response of the rat small-intestine epithelium to methotrexate. Gut 1980; 21: 486-492
- 16. Gibson RJ, Keefe DM, Thompson FM, et al. Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats. Dig Dis Sci. 2002; 47: 2751–2757
- 17. Gulgun M, Erdem O, Oztas E, et al. Proanthocyanidin prevents methotrexate-induced intestinal damage and oxidative stress. Exp Toxicol Pathol 2010; 62: 109-115
- 18. Noé JE. L-Glutamine use in the treatment and prevention of mucositis and cachexia: a naturopathic perspective. Integr Cancer Ther. 2009 8:409–415
- 19. Miller AL. Therpeutic Considerations of L-Glutamine : A Review of the Literature Altren Med Rev 1999; 4: 239-248
- 20. Gaurav K, Goel RK, Shukla M, et al. Glutamine: A novel approach to chemotherapy-induced toxicty. Indian J Med Paediatr Oncol. 2012; 33: 13-20
- 21. Fox AD, Kripke SA, De Paula J, et al. Effect of a glutamine-suplemented enteral diet on methotrexate-induced enterocolitis. JPEN J Parenter Enteral Nutr 1988;12:325-331
- 22. Erbil Y, Oztezcan S, Giriş M, et al. The effect of glutamine on radiation-induced organ damage. Life Sci. 2005;78:376-382
- 23. Williams JZ, Abumrad N, Barbul A. Effect of a Specialized Amino Acid Mixture on Human Collagen Deposition. Ann Surg 2002;236:369-374
- 24. Peterson A, Qureshi MA, Ferket PR, et al. In vitro exposure with [beta]-hydroxy-[beta]-methylbutyrate enhances chicken macrophage growth and function. Vet Immunol Immunopathol 1999; 67:67-78
- 25. Eley HL, Russell ST, Tisdale MJ. Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by β-hydroxy-β-methylbutyrate. Am J Physiol Endocrinol Metab. 2008; 295: 1409-1416
- 26. Eley HL, Russell ST, Tisdale MJ. Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-a and angiotensin II by β-hydroxy-β- methylbutyrate. Am J Physiol Endocrinol Metab. 2008; 295: 1417-1426
- 27. Eley HL, Russell ST, Baxter JH, et al. Signaling pathways initiated by β-hydroxy-β- methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab. 2007; 293: 923-931
- 28. Manzano M, Giron MD, Salto R, et al. Is β-hydroxy-β-methylbutyrate (HMB) the bioactive metabolite of L-leucine (LEU) in muscle? Molecular evidence and potential implications. Abstract presented at: European Society for Clinical Nutrition and Metabolism 31st Congress; Vienna, Austria; 2009. Abstract P267
- 29. Sukhotnik I, Shehadeh N, Coran AG, et al. Oral insulin enhances cell proliferation and decreases enterocyte apoptosis during methotrexate-induced mucositis in the rat. J Pediatr Gastroenterol Nutr 2008;47:115-122