6. Declaration
Ethical Approval: All experiments followed the guidelines for the Care and Use of Laboratory Animals 8th Edition (2011), that is adopted by the Institutional Animal Care and Use Committee (IACUC) of Cairo University, Approval number: (CU, III, F, 81, 18).Consent to Participate: Not applicableConsent to Publish: Not applicableAvailability of data and materials: available upon requestCode availability: not applicableAuthor contributions: OAN, MIA, NEE and WMH have made substantial contributions to conception and design. OAN has made substantial contributions to conduction of the research, acquisition of data, their analysis, their interpretation and wrote the manuscript. All authors have given final approval of the version to be published. The authors declare that all data were generated in-house and that no paper mill was used.Funding: This study was financially supported by the Department of medical pharmacology, Cairo University, Egypt. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Acknowledgements The authors wish to thank Dr Laila Rashed, Professor of Biochemistery, Faculty of Medicine, Cairo University, Egypt, for the biochemical results in this study.7. References
  1. Lennard-Jones JE. Classification of inflammatory bowel disease. Scandinavian Journal of Gastroenterology. 1989 Jan 1;24(sup170):2-6.
  2. Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 2011; 474:298.
  3. Brubaker PL, Drucker DJ. Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Receptors and Channels. 2002 Jan 1;8(3-4):179-88.
  4. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. The Lancet. 2006 Nov 11; 368(9548):1696-705.
  5. Wallace K, MacNaughton & Keith A. Sharkey. Goodman and Gilman’s Manual of Pharmacology and Therapeutics13th edition. 2018; 964-973.
  6. Tavares W, Drucker DJ, Brubaker PL. Enzymatic-and renal-dependent catabolism of the intestinotropic hormone glucagon-like peptide-2 in rats. American Journal of Physiology-Endocrinology And Metabolism. 2000 Jan 1; 278(1): E134-9.
  7. Dube PE, Rowland KJ, Brubaker PL. Glucagon-like peptide-2 activates beta-catenin signaling in the mouse intestinal crypt: role of insulin-like growth factor-I. Endocrinology 2008;149:291–301.
  8. Filippatos TD, Athyros VG, Elisaf MS. The pharmacokinetic considerations and adverse effects of DDP-4 inhibitors. Expert opinion on drug metabolism & toxicology. 2014 Jun 1;10(6):787-812.
  9. Powers AC, D’Alessio D. Endocrine pancreas and pharmacotherapy of diabetes mellitus and hypoglycemia. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13th Edition, McGraw-Hill, New York. 2018:863-885.
  10. Dejardin E. The alternative NF-κB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochemical pharmacology. 2006 Oct 30;72(9):1161-79.
  11. Shinjo T, Nakatsu Y, Iwashita M, Sano T, Sakoda H, Ishihara H, Kushiyama A, Fujishiro M, Fukushima T, Tsuchiya Y, Kamata H. DPP-IV inhibitor anagliptin exerts anti-inflammatory effects on macrophages, adipocytes, and mouse livers by suppressing NF-κB activation. American Journal of Physiology-Endocrinology and Metabolism. 2015 Aug 1;309(3): E214-23
  12. Low D, Nguyen DD, Mizoguchi E. Animal models of ulcerative colitis and their application in drug research. Drug design, development and therapy 2013; 7:1341.
  13. Bang-Berthelsen CH, Holm TL, Pyke C, Simonsen L, Søkilde R, Pociot F, Heller RS, Folkersen L, Kvist PH, Jackerott M, Fleckner J. GLP-1 induces barrier protective expression in Brunner’s glands and regulates colonic inflammation. Inflammatory bowel diseases. 2016 Sep 1; 22(9):2078-97.
  14. Elkatary R, Abdelrahman K, Hassanin A, Elmasry AI, El Karef A, Abdalla HA. Effect of Different Doses of Sitagliptin in Treatment of Experimentally Induced Colitis in Mice. British J Pharma Sci 2015; Jan 1.
  15. Xiao Q, Boushey RP, Cino M, Drucker DJ, Brubaker PL. Circulating levels of glucagon-like peptide-2 in human subjects with inflammatory bowel disease. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 2000; 1; 278(4):R1057-63.
  16. Yazbek R, Howarth G, Geier M, Demuth H, Abbott C. Inhibiting dipeptidyl peptidase activity partially ameliorates colitis in mice (Doctoral dissertation, Frontiers in Bioscience)2008.
  17. Chan YH (2003a): Biostatistics102: Quantitative Data – Parametric & Non-parametric Tests. Singapore Med J.;44(8): 391-396.
  18. Chan YH (2003b): Biostatistics 103: Qualitative Data –Tests of Independence. Singapore Med J.;44(10): 498-503.
  19. Daneshmand A, Rahimian R, Mohammadi H, Ejtemaee-Mehr S, Tavangar SM, Kelishomi RB, Dehpour AR. Protective effects of lithium on acetic acid-induced colitis in rats. Digestive diseases and sciences. 2009 Sep 1;54(9):1901-7.
  20. Abdel-Daim MM, Farouk SM, Madkour FF, Azab SS. Anti-inflammatory and immunomodulatory effects of Spirulina platensis in comparison to Dunaliella salina in acetic acid-induced rat experimental colitis. Immunopharmacology and immunotoxicology. 2015 Mar 4;37(2):126-39.
  21. Li Q, Verma IM. NF-κB regulation in the immune system. Nature Reviews Immunology. 2002 Oct; 2(10):725-34
  22. Dejardin E. The alternative NF-κB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochemical pharmacology. 2006 Oct 30;72(9):1161-79.
  23. Pallone F, Monteleone G. Mechanisms of tissue damage in inflammatory bowel disease. Current opinion in gastroenterology. 2001 Jul 1;17(4):307-12.
  24. Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. The Journal of clinical investigation. 2007 Mar 1;117(3):514-21.
  25. Al-Dwairi A, Alqudah TE, Al-Shboul O, Alqudah M, Al-Dwairi A, Alqudah TE, Al-Shboul O, Alqudah M, Mustafa AG, Alfaqih MA. Glucagon-Like Peptide-1 Exerts Anti-Inflammatory Effects On Mouse Colon Smooth Muscle Cells Through The Cyclic Adenosine Monophosphate/Nuclear Factor-κB Pathway In Vitro [Corrigendum]. Journal of Inflammation Research. 2019;12:267.
  26. Azmy Nabeh O, Attallah MI, El‐Gawhary NE. The pivotal relation between glucagon‐like peptides, NFκB and inflammatory bowel disease. Clinical and Experimental Pharmacology and Physiology. 2020; doi.org/10.1111/1440-1681.13361
  27. Weaver CT, Elson CO, Fouser LA, Kolls JK. The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annual Review of Pathology: Mechanisms of Disease. 2013 Jan 24; 8:477-512.
  28. Archer NK, Adappa ND, Palmer JN, Cohen NA, Harro JM, Lee SK, Miller LS, Shirtliff ME. Interleukin-17A (IL-17A) and IL-17F are critical for antimicrobial peptide production and clearance of Staphylococcus aureus nasal colonization. Infection and immunity. 2016 Dec 1;84(12):3575-83.
  29. Peppercorn MA, Goldman P.The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. Journal of Pharmacology and Experimental Therapeutics.1972; 181:555-562.
  30. Wahl C, Liptay S, Adler G, Schmid RM. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. The Journal of clinical investigation. 1998 Mar 1;101(5):1163-74.
  31. Schottelius AJ, Baldwin Jr AS. A role for transcription factor NF-kB in intestinal inflammation. International journal of colorectal disease. 1999 Mar 1;14(1):18-28.
  32. Tang ST, Su H, Zhang Q, Tang HQ, Wang CJ, Zhou Q, Wei W, Zhu HQ, Wang Y. Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase. International journal of molecular medicine. 2016 Jun 1;37(6):1558-66.
  33. Xie S, Liu B, Fu S, Wang W, Yin Y, Li N, Chen W, Liu J, Liu D. GLP-2 suppresses LPS-induced inflammation in macrophages by inhibiting ERK phosphorylation and NF-κB activation. Cellular Physiology and Biochemistry. 2014;34(2):590-602.
  34. Broxmeyer HE, Hoggatt J, O’Leary HA, Mantel C, Chitteti BR, Cooper S, Messina-Graham S, Hancock G, Farag S, Rohrabaugh SL, Ou X. Dipeptidyl peptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis. Nature medicine. 2012 Dec;18(12):1786.
  35. El-Akabawy G, El-Sherif NM. Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress. Biomedicine & Pharmacotherapy. 2019 Mar 1;111:841-51.
  36. Kvietys PR, Smith SM, Grisham MB, Manci EA. 5-Aminosalicylic acid protects against ischemia/reperfusion-induced gastric bleeding in the rat. Gastroenterology. 1988 Mar 1;94(3):733-8.
  37. Abdelrahman AM, Al Suleimani Y, Al Za’abi M, Ashique M, Manoj P, Hartmann C, et al. The renoprotective effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on adenine-induced kidney disease in rats. Biomedicine & Pharmacotherapy 2009; 110:667-676.
  38. Huh G, Yoon H, Choi YJ, Shin CM, Park YS, Kim N, et al. Correction: Trends in emergency department visits and hospitalization rates for inflammatory bowel disease in the era of biologics. PloS one 2019; 14:e0216768.
  39. Moustafa PE, Abdelkader NF, El Awdan SA, El‐Shabrawy OA, Zaki HF. Liraglutide ameliorated peripheral neuropathy in diabetic rats: involvement of oxidative stress, inflammation and extracellular matrix remodeling. Journal of neurochemistry. 2018 Jul;146(2):173-85.
  40. Varanasi A, Patel P, Makdissi A, Dhindsa S, Chaudhuri A, Dandona P. Clinical use of liraglutide in type 2 diabetes and its effects on cardiovascular risk factors. Endocrine Practice. 2012 Mar 1;18(2):140-5.
  41. Omolekulo TE, Michael OS, Olatunji LA. Dipeptidyl peptidase-4 inhibition protects the liver of insulin-resistant female rats against triglyceride accumulation by suppressing uric acid. Biomedicine & Pharmacotherapy 2019; 110:869-877.
  42. Mega C, Teixeira de Lemos E, Vala H, Fernandes R, Oliveira J, Mascarenhas-Melo F, Teixeira F, Reis F. Diabetic nephropathy amelioration by a low-dose sitagliptin in an animal model of type 2 diabetes (Zucker diabetic fatty rat). Experimental diabetes research. 2011 Nov 30; 2011
  43. Tremblay AJ, Lamarche B, Deacon CF, Weisnagel SJ, Couture P. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Metabolism. 2014 Sep 1;63(9):1141-8.
  44. Lynch L, Hogan AE, Duquette D, Lester C, Banks A, LeClair K, Cohen DE, Ghosh A, Lu B, Corrigan M, Stevanovic D. iNKT cells induce FGF21 for thermogenesis and are required for maximal weight loss in GLP1 therapy. Cell metabolism. 2016 Sep 13;24(3):510-9.
  45. Yusta B, Baggio LL, Koehler J, Holland D, Cao X, Pinnell LJ, Johnson-Henry KC, Yeung W, Surette MG, Bang KA, Sherman PM. GLP-1R agonists modulate enteric immune responses through the intestinal intraepithelial lymphocyte GLP-1R. Diabetes. 2015 Jul 1;64(7):2537-49
  46. Anbazhagan AN, Thaqi M, Priyamvada S, Jayawardena D, Kumar A, Gujral T, Chatterjee I, Mugarza E, Saksena S, Onyuksel H, Dudeja PK. GLP-1 nanomedicine alleviates gut inflammation. Nanomedicine: Nanotechnology, Biology, and Medicine. 2017 Feb 1;13(2):659-65.
  47. Cani PD, Possemiers S, Van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009 Aug 1;58(8):1091-103.
  48. Chiba M, Sanada Y, Kawano S, Murofushi M, Okada I, Yoshizawa Y, Gomi A, Yatsuzuka M, Toki A, Hirai Y. Glicentin inhibits internalization of enteric bacteria by cultured INT-407 enterocytes. Pediatric surgery international. 2007 Jun 1;23(6):551-4.
  49. Gu J, Liu J, Huang T, Zhang W, Jia B, Mu N, Zhang K, Hao Q, Li W, Liu W, Zhang W. The protective and anti-inflammatory effects of a modified glucagon-like peptide-2 dimer in inflammatory bowel disease. Biochemical pharmacology. 2018 Sep 1;155:425-33.
  50. Moran GW, O’Neill C, Padfield P, McLaughlin JT. Dipeptidyl peptidase-4 expression is reduced in Crohn’s disease. Regulatory peptides. 2012 Aug 20;177(1-3):40-5.
  51. Salaga M, Mokrowiecka A, Zielinska M, Malecka-Panas E, Kordek R, Kamysz E, Fichna J. New peptide inhibitor of dipeptidyl peptidase IV, EMDB-1 extends the half-life of GLP-2 and attenuates colitis in mice after topical administration. Journal of Pharmacology and Experimental Therapeutics. 2017 Oct 1;363(1):92-103.
  52. Higashijima Y, Tanaka T, Yamaguchi J, Tanaka S, Nangaku M. Anti-inflammatory role of DPP-4 inhibitors in a nondiabetic model of glomerular injury. American Journal of Physiology-Renal Physiology. 2015 Apr 15;308(8):F878-87.
  53. Yazbeck R, Saluda ML, Howarth GS, Bleich A, Raber K, von Hörsten S, Holst JJ, Abbott CA. Dipeptidyl peptidase expression during experimental colitis in mice. Inflammatory bowel diseases. 2010 Aug 1; 16(8):1340-51.
  54. Abrahami D, Douros A, Yin H, Yu OH, Renoux C, Bitton A, Azoulay L. Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel disease among patients with type 2 diabetes: a population-based cohort study. BMJ. 2018 Mar 21;360:k872.
  55. Radel JA, Pender DN, Shah SA. Dipeptidyl peptidase-4 inhibitors and inflammatory bowel disease risk: a meta-analysis. Annals of Pharmacotherapy. 2019 Jul;53(7):697-704.
  56. Haas RM, Li P, Chu JW. Glucose-lowering effects of sulfasalazine in type 2 diabetes. Diabetes care. 2005 Sep 1;28(9):2238-9.
  57. Stamatiades GA, Echouffo-Tcheugui JB, Garber JR. Sulfasalazine-induced hypoglycemia in a patient with type 2 diabetes and end-stage renal disease. AACE Clinical Case Reports. 2018 Nov 1;4(6):e493-6.
  58. Sehra S, Jaggi S, Sehra D, Aggarwal R, Saraswat V, Juneja D. Management of sitagliptin and metformin combination toxic overdose. J Assoc Physicians India 2016; 64:80-81.