Skip to main content Accessibility help
×
Home

Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats

  • Deniz Güney Duman (a1), Zarife Nigâr Özdemir Kumral (a2), Feriha Ercan (a3), Mustafa Deniz (a4), Güray Can (a5) and Berrak Çağlayan Yeğen (a2)...

Abstract

Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTX-induced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

Copyright

Corresponding author

*Corresponding author: D. G. Duman, email gduman@marmara.edu.tr

References

Hide All
1Dalmasso, G, Cottrez, F, Imbert, V, et al. (2006) Saccharomyces boulardii inhibits inflammatory bowel disease by trapping T cells in mesenteric lymph nodes. Gastroenterology 131, 18121825.
2Hempel, S, Newberry, SJ & Maher, AR (2012) Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA 307, 19591969.
3Buts, JP, De Keyser, N & Raedemaeker, L (1994) Saccharomyces boulardii enhances rat intestinal enzyme expression by endoluminal release of polyamines. Pediatr Res 36, 522527.
4Buts, JP, Bernasconi, P, Vaerman, JP, et al. (1990) Stimulation of secretory Ig A and secretory component of immunoglobulins in small intestine of rats treated with Saccharomyces boulardii. Dig Dis Sci 35, 251256.
5Pothoulakis, C (2009) Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardii. Aliment Pharmacol Ther 15, 826833.
6McFarland, LV (2010) Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol 14, 22022222.
7Bartlett, JG (2002) Clinical practice. Antibiotic-associated diarrhea. N Engl J Med 346, 334339.
8Drehobl, MA, De Salvo, MC, Lewis, DE, et al. (2005) Single-dose azithromycin microspheres vs clarithromycin extended release for the treatment of mild-to-moderate community-acquired pneumonia in adults. Chest 128, 22302237.
9McKenna, S & Evans, G (2001) Macrolides: a Canadian Infectious Disease Society position paper. Can J Infect Dis 12, 218231.
10Leitner, JM, Graninger, W & Thalhammer, F (2010) Hepatotoxicity of antibacterials: pathomechanisms and clinical. Infection 38, 311.
11Olivet, J, Cowan, KH & Curt, GA (1983) The pharmacology and clinical use of methotrexate. N Engl J Med 309, 10941104.
12Curd, CD, Manno, JE & Stewart, JJ (1985) Effects of methotrexate on intestinal transit in rats. Fundam Appl Toxicol 5, 991996.
13Jahovic, N, Sener, G, Cevik, H, et al. (2004) Amelioration of methotrexate-induced enteritis by melatonin in rats. Cell Biochem Funct 22, 169178.
14Buts, JP, Bernasconi, P & Craynest, MPV (1986) Response of human and rat small intestinal mucosa to oral administration of Saccharomyces boulardii. Pediatr Res 20, 192196.
15Blehaut, H, Massot, J & Elmer, GW (1989) Disposition kinetics of Saccharomyces boulardii in man and rat. Biopharm Drug Dispos 10, 353364.
16Kim, YC, Lee, JH, Kim, SH, et al. (2005) Effect of CYP3A1(23) induction on clarithromycin pharmacokinetics in rats with diabetes mellitus. Antimicrob Agents Chemother 49, 25282532.
17Udassin, R, Eimerl, D, Schiffman, J, et al. (1994) Epidural anesthesia accelerates the recovery of postischemic bowel motility in the rat. Anesthesiology 80, 832836.
18Bradley, PP, Priebat, DA, Christersen, RD, et al. (1982) Measurement of cutaneous inflammation. Estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78, 206209.
19Aykaç, G, Uysal, M, Yalçin, AS, et al. (1985) The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 36, 7176.
20Casini, AF, Ferrali, M, Pompella, A, et al. (1986) Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene-intoxicated mice. Am J Pathol 123, 520531.
21Sener, G, Eksioglu-Demiralp, E, Cetiner, M, et al. (2006) l-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death. Cell Biol Toxicol 22, 4760.
22Peeters, TL (1993) Erythromycin and other macrolides as prokinetic agents. Gastroenterology 105, 18861899.
23Bortolotti, M, Mari, C, Brunelli, F, et al. (1999) Effect of intravenous clarithromycin on interdigestive gastroduodenal motility of patients with functional dyspepsia and Helicobacter pylori gastritis. Dig Dis Sci 44, 24392442.
24Rodrigues, AD, Roberts, EM, Mulford, DJ, et al. (1997) Oxidative metabolism of clarithromycin in the presence of human liver microsomes. Major role for the cytochrome P4503A (CYP3A) subfamily. Drug Metab Dispos 25, 623630.
25Pessayre, D, Tinel, M, Larrey, D, et al. (1983) Inactivation of cytochrome P-450 by a troleandomycin metabolite. Protective role of glutathione. J Pharmacol Exp Ther 224, 685691.
26Johnston, BC, Supina, AL, Ospina, M, et al. (2007) Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database of Systematic Reviews, issue 2 CD004827.
27Duman, DG, Bor, S, Ozutemiz, O, et al. (2005) Efficacy and safety of Saccharomyces boulardii in prevention of antibiotic-associated diarrhoea due to Helicobacter pylori eradication. Eur J Gastroenterol Hepatol 17, 13571361.
28Peran, L, Camuesco, D, Comalada, M, et al. (2005) Preventative effects of a probiotic, Lactobacillus salivarius ssp. salivarius, in the TNBS model of rat colitis. World J Gastroenterol 11, 51855192.
29Chen, X, Kokkotou, EG, Mustafa, N, et al. (2006) Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against Clostridium difficile toxin A-induced enteritis. J Biol Chem 281, 2444924454.
30Mumy, KL, Chen, X, Kelly, CP, et al. (2008) Saccharomyces boulardii interferes with Shigella pathogenesis by postinvasion signaling events. Am J Physiol Gastrointest Liver Physiol 294, G599G609.
31Sougioultzis, S, Simeonidis, S, Bhaskar, KR, et al. (2006) Saccharomyces boulardii produces a soluble antiinflammatory factor that inhibits NF-kappaB-mediated IL-8 gene expression. Biochem Biophys Res Commun 343, 6976.
32Xue, H, Sawyer, MB, Wischmeyer, PE, et al. (2011) Nutrition modulation of gastrointestinal toxicity related to cancer chemotherapy: from preclinical findings to clinical strategy. JPEN J Parenter Enteral Nutr 35, 7490.
33Sonis, ST, Elting, LS, Keefe, DMK, et al. (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100, 19952025.
34Lee, SK, Kim, YW, Chi, SG, et al. (2009) The effect of Saccharomyces boulardii on human colon cells and inflammation in rats with trinitrobenzene sulfonic acid-induced colitis. Dig Dis Sci 54, 255263.
35Sezer, A, Usta, U & Cicin, I (2009) The effect of Saccharomyces boulardii on reducing irinotecan-induced intestinal mucositis and diarrhea. Med Oncol 26, 350357.
36Forestier, C, De Champs, C & Vatoux, C (2001) Probiotic activities of Lactobacillus casei rhamnosus: in vitro adherence to intestinal cells and antimicrobial properties. Res Microbiol 152, 167173.
37Isolauri, E (2001) Probiotics in human disease. Am J Clin Nutr 73, 1142S1146S.
38Tooley, KL, Howarth, GS, Lymn, KA, et al. (2006) Oral ingestion of Streptococcus thermophilus diminishes severity of small intestinal mucositis in methotrexate treated rats. Cancer Biol Ther 5, 593600.
39Generoso, SV, Viana, ML, Santos, RG, et al. (2011) Protection against increased intestinal permeability and bacterial translocation induced by intestinal obstruction in mice treated with viable and heat-killed Saccharomyces boulardii. Eur J Nutr 50, 261269.
40Zanello, G, Meurens, F, Berri, M, et al. (2011) Saccharomyces cerevisiae decreases inflammatory responses induced by F4+ enterotoxigenic Escherichia coli in porcine intestinal epithelial cells. Vet Immunol Immunopathol 141, 133138.
41Jawhara, S, Habib, K, Maggiotto, F, et al. (2012) Modulation of intestinal inflammation by yeasts and cell wall extracts: strain dependence and unexpected anti-inflammatory role of glucan fractions. PLoS One 7, e40648.
42Lessard, M, Dupuis, M, Gagnon, N, et al. (2009) Administration of Pediococcus acidilactici or Saccharomyces cerevisiae boulardii modulates development of porcine mucosal immunity and reduces intestinal bacterial translocation after Escherichia coli challenge. J Anim Sci 87, 922934.
43Akyol, S, Mas, MR, Comert, B, et al. (2003) The effect of antibiotic and probiotic combination therapy on secondary pancreatic infections and oxidative stress parameters in experimental acute necrotizing pancreatitis. Pancreas 26, 363367.

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed