The effectiveness of hesperidin in the prevention of bacterial translocation caused by methotrexate in the Gastrointestinal tract
Metotreksatı (MTX) çocukluk çağı kanserlerinde yaygın olarak kullanılan antimetabolittir. Oksidatif hasardan kaynaklanan gastrointestinal toksisite MTX için önemli bir sınırlayıcı faktördür. MTX’in ince barsak mukozasında morfolojik hasar ve ciddi bariyer fonksiyon bozukluğuna neden olur. Barsak bariyer fonksiyonları bozulduğu zaman, bakteriyel translokasyon görülebilir. Bu çalışmanın amacı, MTX’in neden olduğu bakteriyel translokasyonun önlenmesinde güçlü bir antioksidan olan hesperidinin etkisini değerlendirmektir. Sıçanlara MTX tek doz intraperitoneal yoldan 20 mg/kg/gün verildi. İntestinal bakteriyel translokasyonu önlemek için ardışık 5 gün hesperidin 200 mg/kg/gün gavaj ile uygulandı. Çalışmanın 6. günü ileoçekal bölge, asendan kolon ve mesenterial lenf nodlarından biyopsi örnekleri kültür vasatlarına alındı. MTX grubunda, barsakta daha fazla üreme ve aynı zamanda belirgin bakteriyel translokasyon saptandı (P
Metotreksatın neden olduğu Gastrointestinal kanaldan bakteriyel translokasyonun önlenmesinde hesperidinin etkinliği
Methotrexate (MTX) is an antimetabolite that it is widely used in childhood cancers. Gastrointestinal toxicity stemming from oxidative damage is an important factor limiting its use. MTX causes morphological damage in the mucosa of the small intestine and serious barrier function disorder. Bacterial translocation can be seen when intestinal barrier functions are deteriorated. The aim of this study was to investigate the effect of hesperidin, a powerful antioxidant, in the prevention of bacterial translocation caused by MTX. Rats were given a single intraperitoneal dose of MTX at 20 mg/kg body weight. Hesperidin was given with oral gavage at 200 mg/kg body weight through 5 days. On the 6th day, biopsy specimens from the ileocecal region, ascending colon and mesenteric lymph nodes were placed in culture media. Increased intestinal bacteria growth was found and prominent bacterial translocation were determined in the MTX group (P<0.05). Hesperidin significantly reduced the growth load and bacterial translocation. This study showed that hesperidin protects against translocation by preventing damage caused by MTX.
___
- 1. Kolli VK, Abraham P, Rabi S: Methotrexate-induced nitrosative stress may play a critical role in small intestinal damage in the rat. Arch Toxicol, 82, 763-770, 2008.
- 2. Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA: The pharmacology and clinical use of methotrexate. N Engl J Med, 309, 1094- 1104, 1983.
- 3. Song D, Shi B, Xue H, Li Y, Yang X, Yu B, Xu Z, Liu F, Li J: Confirmation and prevention of intestinal barrier dysfunction and bacterial translocation caused by methotrexate. Dig Dis Sci, 51, 1549-1556, 2006.
- 4. Soares PM, Lopes LO, Mota JM, Belarmino-Filho JN, Ribeiro RA, Souza MH: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats. Arq Gastroenterol, 48, 80-58, 2011.
- 6. Ciralik H, Bulbuloglu E, Cetinkaya A, Kurutas EB, Celik M, Polat A: Effects of N-acetylcysteine on methotrexate-induced small intestinal damage in rats. Mt Sinai J Med, 73, 1086-1092, 2006.
- 7. Jahovic N, Sener G, Cevik H, Ersoy Y, Arbak S, Yegen BC: Amelioration of methotrexate-induced enteritis by melatonin in rats. Cell Biochem Funct, 22, 169-178, 2004.
- 8. Yuncu M, Eralp A, Koruk M, Sari I, Bagci C, Inaloz S: Effect of vitamin A against methotrexate-induced damage to the small intestine in rats. Med Princ Pract, 13, 346-352, 2004.
- 9. Horie T, Matsumoto H, Kasagi M, Sugiyama A, Kikuchi M, Karasawa C, Awazu S, Itakura Y, Fuwa T: Protective effect of aged garlic extract on the small intestinal damage of rats induced by methotrexate administration. Planta Med, 65, 545-548, 1999.
- 10. Guardia T, Rotelli AE, Juardez AO, Pelzer LE: Anti-inflammatory properties of plant flavonoids. Effect of rutin, quarcetin and hesperidin on adjuvant arthritis in rat. Farmaco, 56, 683-687, 2001.
- 11. Koyuncu H, Berkarda B, Baykut F, Soybir G, Alatli C, Gül H, Altun M: Preventive effect of hesperidin against inflammation in CD-1 mouse skin caused by tumor promoter. Anticancer Res, 19, 3237-3241, 1999.
- 12. Garg A, Garg S, Zaneveld LJ, Singla AK: Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res, 15, 655-669, 2001.
- 13. Alamir I, Boukhettala N, Aziz M, Breuillé D, Déchelotte P, Coëffier M: Beneficial effects of cathepsin inhibition to prevent chemotherapy- induced intestinal mucositis. Clin Exp Immunol, 162, 298-305, 2010.
- 14. Boukhettala N, Leblond J, Claeyssens S, Faure M, Le Pessot F, Bôle-Feysot C, Hassan A, Mettraux C, Vuichoud J, Lavoinne A, Breuillé D, Déchelotte P, Coëffier M: Methotrexate induces intestinal mucositis and alters gut protein metabolism independently of reduced food intake. Am J Physiol Endocrinol Metab, 296, 182-190, 2009.
- 15. Berg RD: Bacterial translocation from the gastrointestinal tract. Trends Microbiol, 3, 149-154, 1995.
- 16. Owens WE, Berg RD: Bacterial translocation from the gastrointestinal tract of athymic (nu/nu) mice. Infect Immun, 27, 461-467, 1980.
- 17. Van Leeuwen PA, Boermeester MA, Houdijk AP, Ferwerda CC, Cuesta MA, Meyer S, Wesdorp RI: Clinical significance of translocation. Gut, 35, 28-34, 1994.
- 18. Maejima K, Deitch EA, Berg RD: Bacterial translocation from the gastrointestinal tracts of rats receiving thermal injury. Infect Immun, 43, 6-10, 1984.
- 19. Baker JW, Deitch EA, Li M, Berg RD, Specian RD: Hemorrhagic shock induces bacterial translocation from the gut. J Trauma, 28, 896-906, 1988.
- 20. Deitch EA, Berg R, Specian R: Endotoxin promotes the translocation of bacteria from the gut. Arch Surg, 122, 185-190, 1987.
- 21. Ambrose NS, Johnson M, Burdon DW, Keighley MR: Incidence of pathogenic bacteria from mesenteric lymph nodes and ileal serosa during Crohn’s disease surgery. Br J Surg, 71, 623-525, 1984.
- 22. Berg RD, Garlington AW: Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model. Infect Immun, 23, 403- 411, 1979.
- 23. Carneiro-Filho BA, Lima IP, Araujo DH, Cavalcante MC, Carvalho GH, Brito GA, Lima V, Monteiro SM, Santos FN, Ribeiro RA, Lima AA: Intestinal barrier function and secretion in methotrexate-induced rat intestinal mucositis. Dig Dis Sci, 49, 65-72, 2004.
- 24. Berg R: Bacterial translocation from the gastrointestinal tract. Adv Exp Med Biol, 473, 11-30, 1999.
- 25. Cruz N, Alvarez X, Berg R, Deitch EA: Bacterial translocation across enterocytes: Results of a study of bacterial-enterocyte interactions utilizing Caco-2 cells. Shock, 1, 67-72, 1994.
- 26. Hou M, Man M, Man W, Zhu W, Hupe M, Park K, Crumrine D, Elias PM, Man MQ: Topical hesperidin improves epidermal permeability barrier function and epidermal differentiation in normal murine skin. Exp Dermatol, 21, 337-340, 2012.
- 27. Xu L, Yang ZL, Li P, Zhou YQ: Modulating effect of Hesperidin on experimental murine colitis induced by dextran sulfate sodium. Phytomedicine, 16, 989-995, 2009.