Volume 27, Issue 3 (September 2023)                   Physiol Pharmacol 2023, 27(3): 283-295 | Back to browse issues page

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Dovbynchuk T, Chervinska T, Zakordonets L, Huet A, Serhiichuk T, Ostapchenko L et al . The effect of broad-spectrum antibiotic ceftriaxone on net colonic water and ion transport in vivo. Physiol Pharmacol 2023; 27 (3) :283-295
URL: http://ppj.phypha.ir/article-1-1848-en.html
The effect of broad-spectrum antibiotic ceftriaxone on net colonic water and ion transport in vivo
Taisa Dovbynchuk , Tetiana Chervinska , Liudmyla Zakordonets , Alevtina Huet , Tetiana Serhiichuk , Liudmyla Ostapchenko , Ganna Tolstanova
Abstract:   (1133 Views)

Introduction: The molecular mechanism of idiopathic antibiotic-associated diarrhea is not clear. Сeftriaxone, a third-generation cephalosporin, is a broad-spectrum antibiotic and diarrhea is the main side-effect of ceftriaxone treatment. The present study tested the hypothesis that ceftriaxone-induced diarrhea is associated with a shift in microbiota composition followed by the alteration in colonic water/ion transport, the expression pattern of transporters and epithelial barrier function.
Methods: Male Wistar rats were treated daily with ceftriaxone (50 mg/kg, i.m.) for 5 or 14 days. Epithelial net water and ion transport (Na+ , K+ , Cl- ) were evaluated on the 6th or 15th day respectively by isolated colonic loop perfusion technique in vivo. Gene expression by RT-PCR, glycoproteins levels by PAS-staining, and microbiota by culture method on the elective medium were evaluated.
Results: Decreases in Na+ and water absorption, surface mucus layer, and Scnn1b and Aqp8 gene expression were associated with more severe diarrhea after 5 days-antibiotic treatment. After 14-days of antibiotic treatment, fewer animals with diarrhea were observed. At the same time, there was a decrease of Cl- and an increase in Na+ absorption, along with increased mucus secretion and upregulation of Cftr, Scnn1b, Slc9a3, Muc2, Ocln, and Tjp1 gene expression. These changes were accompanied by an increase in the number of culturable conditionally pathogenic microbiota after 5 days of treatment which almost returned to the control value after 14 days of treatment.
Conclusion: We concluded that the observed transitory antibiotic-associated diarrhea was a well-orchestrated physiological defense response at the molecular level driven by the shift in normal microbiota composition.

Keywords: Antibiotic-associated diarrhea, Ceftriaxone, Colon, Ion transport, Epithelial barrier
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Type of Manuscript: Experimental research article | Subject: Gastrointestinal Physiology/Pharmacology
References
1. Akiba Y, Guth PH, Engel E, Nastaskin I, Kaunitz JD. Dynamic regulation of mucus gel thickness in rat duodenum. Am J Physiol Gastrointest Liver Physiol 2000; 279(2): G437–47. [DOI:10.1152/ajpgi.2000.279.2.G437]
2. Benjamin HM, Horace RTW. Clostridium difficile infection and antibiotic-associated diarrhea. Clin Med (Lond) 2018; 18(3): 237–41. [DOI:10.7861/clinmedicine.18-3-237]
3. Camilleri M, Carlson P, Chedid V, Vijayvargiya P, Burton D, Busciglio I. Aquaporin Expression in Colonic Mucosal Biopsies From Irritable Bowel Syndrome With Diarrhea. Clin Transl Gastroenterol 2019; 10(4), e00019. [DOI:10.14309/ctg.0000000000000019]
4. Chelakkot C, Ghim J. Ryu SH. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med 2018; 50, 103. [DOI:10.1038/s12276-018-0126-x]
5. Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: twenty-something years on. Nature Protocols 2006; 1(2), 581–5. [DOI:10.1038/nprot.2006.83.]
6. Dovbynchuk T, Zakordonets L, Baban V, Chervinska T, Tolstanova G. The effect of multi-spicies probiotic on antibiotic-induced changes in colonic ion and water transport. Res J Pharma, Biol Chem Sci 2015a; 6(6): 896-901. [DOI:10.1111/j.1572-0241.2007.01547.x]
7. Dovbynchuk T, Zakordonets L, Putnikov A, Vareniuk I, Tiapko О, Roslova N, et al. Net water transport via rat colon epitelium under the experimental dysbiosis. Fiziol Zh 2015b; 61(6):76-85. [DOI:10.15407/fz61.06.076]
8. Durham SH, Wingler MJ, Eiland LS. Appropriate Use of Ceftriaxone in the Emergency Department of a Veteran’s Health Care System. J Pharm Technol 2017; 33(6):215-8. [DOI:10.1177/8755122517720293]
9. Gareau MG, Barrett KE. Fluid and electrolyte secretion in the inflamed gut: novel targets for treatment of inflammation-induced diarrhea. Curr Opin Pharmacol 2013; 13(6): 895–9. [DOI:10.1016/j.coph.2013.08.014]
10. Ghosh S, Dai C, Brown K, Rajendiran E, Makarenko S, Baker J, Gibson DL. Colonic microbiota alters host susceptibility to infectious colitis by modulating inflammation, redox status, and ion transporter gene expression Am J of Physiol. Gastrointest and Liver Physiol 2011; 301(1): G39-49. [DOI:10.1152/ajpgi.00509.2010]
11. Giannella RA, Serumag J, Walls D, Drake KW. Effect of clindamycin on intestinal water and glucose transport in the rat. Gastroenterology 1981; 80(5 pt 1): 907-13. [DOI:10.1016/0016-5085(81)90058-5.]
12. Goldhill JM, Rose K, Percy WH. Effects of antibiotics on epithelial ion transport in the rabbit distal colon in-vitro. J Pharm Pharmacol 1996; 48(6):651-6. [DOI:10.1111/j.2042-7158.1996.tb05990.x]
13. Gustafsson JK, Navabi N, Rodriguez-Piñeiro AM, Alomran AHA, Premaratne P, Fernandez HR, et al. Dynamic changes in mucus thickness and ion secretion during Citrobacter rodentium infection and clearance. PloS one 2013; 8(12): e84430. [DOI:10.1371/journal.pone.0084430]
14. Holota Y, Dovbynchuk T, Kaji I, Vareniuk I, Dzyubenko N, Chervinska T, et al. The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and https://intestinal barrier integrity. PLoS One 2019; 14(8): e0220642. [DOI:10.1371/journal.pone.0220642]
15. Hoque KM, Chakraborty S, Sheikh IA. Woodward OM. New advances in the pathophysiology of intestinal ion transport and barrier function in diarrhea and the impact on therapy. Expert Rev Anti Infect Ther 2012; 10(6): 687-99. [DOI:10.1586/eri.12.47]
16. Hove H, Tvede M, Mortensen PB. Antibiotic-associated diarrhoea, Clostridium difficile, and short-chain fatty acids. Scand J Gastroenterol 1996; 31(7): 688-93. [DOI:10.3109/00365529609009151]
17. Kiela PR, Ghishan FK. Ion transport in the intestine. Curr Opin Gastroenterol 2009; 25(2): 87-91. [DOI:10.1097/MOG.0b013e3283260900]
18. Konturek PC, Brzozowski T, Pierzchalski P, Kwiecien S, Pajdo R, Hahn EG, et al. Activation of genes for spasmolytic peptide, transforming growth factor alpha and for cyclooxygenase (COX)-1 and COX-2 during gastric adaptation to aspirin damage in rats. Aliment Pharmacol Ther 1998; 12(8): 767-77. [DOI:10.1046/j.1365-2036.1998.00371.x]
19. Kunzelmann K, Mall M. Electrolyte transport in the mammalian colon: mechanisms and implications for disease. Physiol Rev 2002; 82(1): 245-89. [DOI:10.1152/physrev.00026.2001]
20. Liu Q, Yu Z, Tian F. et al. Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier. Microb Cell Fact 2020; 19, 23. [DOI:10.1186/s12934-020-1289-4]
21. Liu Q, Yu Z, Tian F, Zhao J, Zhang H, Zhai Q, et al. Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier. Microb Cell Fact 2020; 19, 23. [DOI:10.1186/s12934-020-1289-4]
22. Lomasney KW, Hyland NP. The application of Ussing chambers for determining the impact of microbes and probiotics on intestinal ion transport. Can J Physiol Pharmacol 2013; 91(9): 663-70. [DOI:10.1139/cjpp-2013-0027]
23. Marchelletta RR, Gareau MG, McCole DF, Okamoto S, Roel E, Klinkenberg R, et al. Altered expression and localization of ion transporters contribute to diarrhea in mice with Salmonella-induced enteritis. Gastroenterology 2013; 145(6): 1358–68.e1–4. [DOI:10.1053/j.gastro.2013.08.054]
24. National Research Council. Guide for the Care and Use of Laboratory Animals: Eighth Edition. Washington, DC: The National Academies Press. 2011. [DOI:10.17226/12910]
25. Nelson Rl, Kelsey P, Leeman H, Meardon N, Patel H, et al. Antibiotic treatment for Clostridium difficile -associated diarrhea in adults ( Review ). Cochrane Database Syst Rev 2011; (9):CD004610. [DOI:10.1002/14651858.CD004610.pub4]
26. Neuman G, Boodhan S, Wurman I, Koren G, Bitnun A, et al. Ceftriaxone-induced immune hemolytic anemia. Ann Pharmacother 2014; 48(12): 1594-1604. [DOI:10.1177/1060028014548310.]
27. Piliponsky AM, Romani L. The contribution of mast cells to bacterial and fungal infection immunity. Immunol Rev 2018; 282(1):188-97. [DOI:10.1111/imr.12623]
28. Roberts M, Hladky SB, Pickles RJ, Cuthbert AW. Stimulation of sodium transport by duramycin in cultured human colonic epithelia. J Pharmacol Exp Ther 1991; 259(3): 1050–8.
29. Sakai H, Sagara A, Matsumoto K, Jo A, Hirosak A, Takase K, Narita M. Neutrophil recruitment is critical for 5-fluorouracil-induced diarrhea and the decrease in aquaporins in the colon. Pharmacol Res 2014; 87: 71–9. [DOI:10.1016/j.phrs.2014.05.012]
30. Sambrook J, Russell DW. Separation of RNA according to size: electrophoresis of glyoxylated RNA through agarose gels. CSH Protoc 2006; 1: 23-8. [DOI:10.1101/pdb.prot4057]
31. Schedl HP. Use of polyethylene glycol and phenol red as unabsorbed indicators for intestinal absorption studies in man. Gut 1966; 7(2): 159-63. [DOI:10.1136/gut.7.2.159]
32. Shubha P, Arivarasu NA, Tarunmeet G, Alip B, Seema S, Ravinder KG, et al. All-trans-retinoic Acid Increases SLC26A3 DRA (Down-regulated in Adenoma) Expression in Intestinal Epithelial Cells via HNF-1β J Biol Chem 2015; 290, 15066-77. [DOI:10.1074/jbc.M114.566356]
33. Sladen GE, Harries JT. Studies on the effects of unconjugated dihydroxy bile salts on rat small intestinal function in vivo. Biochim Biophys Acta. 1972; 288(2): 443-56. [DOI:10.1016/0005-2736 (72)90265-9]
34. Spehlmann ME, Dann SM, Hruz P, Hanson E, McCole DF, Eckmann L. CXCR2-dependent mucosal neutrophil influx protects against colitis-associated diarrhea caused by an attaching/effacing lesion-forming bacterial pathogen. J Immun 2009; 183(5): 3332-43. [DOI:10.4049/jimmunol.0900600]
35. Thomson SR, Ommurugan B, Patil N. Ceftriaxone induced hypersensitivity reactions following intradermal skin test: Case Series. J Clin Diagn Res 2017; 11(10) 3,672. [DOI:10.7860/JCDR/2017/29088.10758]
36. Tomas J, Reygner J, Mayeur C, Ducroc R, Bouet S, Bridonneau C, et al. Early colonizing Escherichia coli elicits remodeling of rat colonic epithelium shifting toward a new homeostatic state. ISME J2015; 9(1): 46-58. [DOI:10.1038/ismej.2014.111]
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