Probiyotiklerin irinotekan ilişkili karaciğer yağlanmasına karşı koruyucu etkisinin araştırılması: Hayvan deneyi modeli
Öz
Giriş ve Amaç: Non-alkolik yağlı karaciğer hastalığı, küresel nüfusun yaklaşık %25'ini etkileyen ve irinotekan kullanan hastaların %20'sinde ilaca bağlı olarak gelişen kronik bir hastalıktır. Non-alkolik yağlı karaciğer hastalığı tedavisi üzerine birçok çalışma yapılmış olmasına rağmen, diyet değişikliği ve egzersize üstün, standart bir tedavi yöntemi henüz keşfedilememiştir. Probiyotiklerin, diyetle ilişkili yağlı karaciğer hastalığı üzerinde olumlu etkileri olduğu gösterilmiştir. Bu çalışma, metastatik kolon-rektum, mide ve pankreas tümörlerinin sistemik tedavi rejimlerinde sıklıkla yer alan irinotekanın neden olduğu non-alkolik yağlı karaciğer hastalığının, probiyotiklerin eşzamanlı kullanımıyla önlenip önlenemeyeceğini araştırmayı amaçlamaktadır. Gereç ve Yöntem: Bu çalışma, hayvan deneyi modeli olarak planlandı ve sekizer fareden oluşan dört grup (normal salin, sadece irinotekan, irinotekan + probiyotik ve yalnız probiyotik) oluşturuldu. Yedi haftalık sürenin sonunda, probiyotik kullanımının etkisi biyokimyasal, histolojik ve immünhistokimyasal analizlerle incelendi. Bulgular: Yapılan incelemeler sonucunda, irinotekan + probiyotik grubunda, sadece irinotekan alan gruba kıyasla steatoz, lobüler inflamasyon, hepatosit balonlaşması, fibrozis, indüklenebilir nitrik oksit sentaz düzeyi, dönüştürücü büyüme faktörü-beta düzeyi ve aspartat aminotransferaz düzeyi açısından istatistiksel olarak anlamlı bir iyileşme gözlemlendi (p < 0.05). Sonuç: Bu çalışmadan elde edilen sonuçlar, irinotekan ile birlikte probiyotik kullanımının, yağlı karaciğer hastalığı ve steatohepatitin gelişimini azaltabileceğini düşündürmektedir.
Anahtar Kelimeler
Kaynakça
- 1. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.
- 2. Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24(13):2065-72.
- 3. Vigano L, De Rosa G, Toso C, et al. Reversibility of chemotherapy-related liver injury. J Hepatol. 2017;67(1):84-91.
- 4. Khalighi A, Behdani R, Kouhestani S. Probiotics: A Comprehensive Review of Their Classification, Mode of Action and Role in Human Nutrition [Internet]. Probiotics and Prebiotics in Human Nutrition and Health. InTech; 2016;19-39. Available from: http://dx.doi.org/10.5772/63646
- 5. Italian Association for the Study of the Liver (AISF). AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions. Dig Liver Dis. 2017;49(5):471-83.
- 6. Nardone G, Compare D, Liguori E, et al. Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G669-76.
- 7. Costa ML, Lima-Júnior RC, Aragão KS, et al. Chemotherapy-associated steatohepatitis induced by irinotecan: a novel animal model. Cancer Chemother Pharmacol. 2014;74(4):711-20.
- 8. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001;21(1):3-16.
- 9. Younossi ZM, Marchesini G, Pinto-Cortez H, Petta S. Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation. Transplantation. 2019;103(1):22-7.
- 10. Zhang X, Fryknäs M, Hernlund E, et al. Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments. Nat Commun. 2014;5:3295.
- 11. Al Khodor S, Shatat IF. Gut microbiome and kidney disease: a bidirectional relationship. Pediatr Nephrol. 2017;32(6):921-31.
- 12. Grąt M, Wronka KM, Krasnodębski M, et al. Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis. Transplant Proc. 2016;48(5):1687-91.
- 13. Wang J, Wang Y, Zhang X, et al. Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients. Front Microbiol. 2017;8:2222
- 14. Chalasani N, Younossi Z, Lavine JE, et al; American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterologyh. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142(7):1592-609.
- 15. Li Z, Yang S, Lin H, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003;37(2):343-50.
- 16. Velayudham A, Dolganiuc A, Ellis M, et al. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology. 2009;49(3):989-97.
- 17. Ma YY, Li L, Yu CH, et al. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013;19(40):6911-8.
- 18. Malaguarnera M, Vacante M, Antic T, et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci. 2012;57(2):545-53.
- 19. Duseja A, Acharya SK, Mehta M, et al. High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): a randomised, double-blind, proof of concept study. BMJ Open Gastroenterol. 2019;6(1):e000315.
- 20. The Liver and Bile Ducts. In Kumar V, Abbas AK, Aster JC (Editors). Robbins Basic Pathology. 10th ed. Elsevier - Health Sciences Division; 2017;637-72.
- 21. Anavi S, Eisenberg-Bord M, Hahn-Obercyger M, et al. The role of iNOS in cholesterol-induced liver fibrosis. Lab Invest. 2015;95(8):914-24.
- 22. Wei CL, Hon WM, Lee KH, Khoo HE. Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats. Liver Int. 2005;25(3):647-56.
- 23. Novitskiy G, Potter JJ, Wang L, Mezey E. Influences of reactive oxygen species and nitric oxide on hepatic fibrogenesis. Liver Int. 2006;26(10):1248-57.
- 24. Beljaars L, Daliri S, Dijkhuizen C, et al. WNT-5A regulates TGF-β-related activities in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2017;312(3):G219-G227.
- 25. Breitkopf K, Haas S, Wiercinska E, et al. Anti-TGF-beta strategies for the treatment of chronic liver disease. Alcohol Clin Exp Res. 2005;29(11 Suppl):121S-131S.
Öz
Background and Aim: Non-alcoholic fatty liver disease is a chronic condition that affects approximately 25% of the global population and develops in 20% of patients using irinotecan. Although many studies have been conducted on the treatment of non-alcoholic fatty liver disease, a standard treatment method superior to diet modification and exercise has not been discovered yet. It has been shown that the use of probiotics has positive effects on diet-related fatty liver disease. This study aimed to investigate whether non-alcoholic fatty liver disease caused by irinotecan, which is frequently included in the systemic treatment regimens of metastatic colon-rectum, stomach, and pancreatic tumors, can be prevented through the concomitant use of probiotics. Material and Methods: In this study, which was planned as an experimental animal model, four groups of eight mice each (normal saline, irinotecan alone, irinotecan + probiotics, and probiotics alone) were formed, and at the end of the seven-week period, the effect of probiotic use was examined using biochemical, histological, and immunohistochemical analyses. Results: As a result of the examinations, a statistically significant improvement was observed in the irinotecan + probiotics group in terms of steatosis, lobular inflammation, hepatocyte ballooning, fibrosis, inducible nitric oxide synthase level, transforming growth factor beta level, and aspartate aminotransferase level compared to the group receiving irinotecan alone (p < 0.05). Conclusion: The results obtained from this study suggest that the concomitant use of probiotics with irinotecan may reduce the development of fatty liver disease and steatohepatitis.
Anahtar Kelimeler
Kaynakça
- 1. Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.
- 2. Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24(13):2065-72.
- 3. Vigano L, De Rosa G, Toso C, et al. Reversibility of chemotherapy-related liver injury. J Hepatol. 2017;67(1):84-91.
- 4. Khalighi A, Behdani R, Kouhestani S. Probiotics: A Comprehensive Review of Their Classification, Mode of Action and Role in Human Nutrition [Internet]. Probiotics and Prebiotics in Human Nutrition and Health. InTech; 2016;19-39. Available from: http://dx.doi.org/10.5772/63646
- 5. Italian Association for the Study of the Liver (AISF). AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions. Dig Liver Dis. 2017;49(5):471-83.
- 6. Nardone G, Compare D, Liguori E, et al. Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury. Am J Physiol Gastrointest Liver Physiol. 2010;299(3):G669-76.
- 7. Costa ML, Lima-Júnior RC, Aragão KS, et al. Chemotherapy-associated steatohepatitis induced by irinotecan: a novel animal model. Cancer Chemother Pharmacol. 2014;74(4):711-20.
- 8. Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis. 2001;21(1):3-16.
- 9. Younossi ZM, Marchesini G, Pinto-Cortez H, Petta S. Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation. Transplantation. 2019;103(1):22-7.
- 10. Zhang X, Fryknäs M, Hernlund E, et al. Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments. Nat Commun. 2014;5:3295.
- 11. Al Khodor S, Shatat IF. Gut microbiome and kidney disease: a bidirectional relationship. Pediatr Nephrol. 2017;32(6):921-31.
- 12. Grąt M, Wronka KM, Krasnodębski M, et al. Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer in Patients With Liver Cirrhosis. Transplant Proc. 2016;48(5):1687-91.
- 13. Wang J, Wang Y, Zhang X, et al. Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients. Front Microbiol. 2017;8:2222
- 14. Chalasani N, Younossi Z, Lavine JE, et al; American Gastroenterological Association; American Association for the Study of Liver Diseases; American College of Gastroenterologyh. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142(7):1592-609.
- 15. Li Z, Yang S, Lin H, et al. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology. 2003;37(2):343-50.
- 16. Velayudham A, Dolganiuc A, Ellis M, et al. VSL#3 probiotic treatment attenuates fibrosis without changes in steatohepatitis in a diet-induced nonalcoholic steatohepatitis model in mice. Hepatology. 2009;49(3):989-97.
- 17. Ma YY, Li L, Yu CH, et al. Effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. World J Gastroenterol. 2013;19(40):6911-8.
- 18. Malaguarnera M, Vacante M, Antic T, et al. Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig Dis Sci. 2012;57(2):545-53.
- 19. Duseja A, Acharya SK, Mehta M, et al. High potency multistrain probiotic improves liver histology in non-alcoholic fatty liver disease (NAFLD): a randomised, double-blind, proof of concept study. BMJ Open Gastroenterol. 2019;6(1):e000315.
- 20. The Liver and Bile Ducts. In Kumar V, Abbas AK, Aster JC (Editors). Robbins Basic Pathology. 10th ed. Elsevier - Health Sciences Division; 2017;637-72.
- 21. Anavi S, Eisenberg-Bord M, Hahn-Obercyger M, et al. The role of iNOS in cholesterol-induced liver fibrosis. Lab Invest. 2015;95(8):914-24.
- 22. Wei CL, Hon WM, Lee KH, Khoo HE. Chronic administration of aminoguanidine reduces vascular nitric oxide production and attenuates liver damage in bile duct-ligated rats. Liver Int. 2005;25(3):647-56.
- 23. Novitskiy G, Potter JJ, Wang L, Mezey E. Influences of reactive oxygen species and nitric oxide on hepatic fibrogenesis. Liver Int. 2006;26(10):1248-57.
- 24. Beljaars L, Daliri S, Dijkhuizen C, et al. WNT-5A regulates TGF-β-related activities in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2017;312(3):G219-G227.
- 25. Breitkopf K, Haas S, Wiercinska E, et al. Anti-TGF-beta strategies for the treatment of chronic liver disease. Alcohol Clin Exp Res. 2005;29(11 Suppl):121S-131S.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Gastroenteroloji ve Hepatoloji |
| Bölüm | Makaleler |
| Yazarlar | |
| Yayımlanma Tarihi | 20 Ağustos 2025 |
| Gönderilme Tarihi | 4 Nisan 2025 |
| Kabul Tarihi | 15 Nisan 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 24 Sayı: 2 |
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