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Volume 15, Issue 3 (2023)
Iran J War Public Health 2023, 15(3): 225-231 |
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Received: 2023/04/24 | Accepted: 2023/05/29 | Published: 2023/06/20
Received: 2023/04/24 | Accepted: 2023/05/29 | Published: 2023/06/20
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Mohammad A, Shnaien A, Alabsawy S, Hassan E. Protective Effect of Ipragliflozin on Acute Brain Injury Induced by Endotoxemia in Mice. Iran J War Public Health 2023; 15 (3) :225-231
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1- Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq
2- Department of Physiology & Pharmacology, Faculty of Veterinary Medicine, University of Kufa, Najaf, Iraq
2- Department of Physiology & Pharmacology, Faculty of Veterinary Medicine, University of Kufa, Najaf, Iraq
Abstract (1254 Views)
Aims: This study was done to investigate the potential neuroprotective effect of ipragliflozin during endotoxemia in mice.
Materials & Methods: Twenty-four adult male Swiss-albino mice aged 8-12 weeks (25-35g) were randomized into four equal groups (n=6): sham (laparotomy without cecal ligation and puncture (CLP), sepsis (laparotomy with CLP), vehicle (equivalent volume of DMSO before CLP), and ipragliflozin (3mg/kg/day, orally before CLP). Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, toll-like receptor 4 (TLR4), and P-signal transducer and activator of transcription (STAT)-3 levels were assessed in the brain tissue and histological examination was done.
Findings: The tissue levels of TNF-α, IL-6, and IL-1B in the sham group were much lower than in the sepsis and vehicle groups. Furthermore, the ipragliflozin group had considerably lower tissue levels of TNF-α, IL-6, and IL-1B compared to the sepsis and vehicle groups. However, the sham group showed much lower tissue levels of TLR4 and STAT3 compared to the sepsis and vehicle groups. Also, the tissue levels of TLR4 and STAT3 in the ipragliflozin group were considerably lower than those in the sepsis and vehicle groups. Histopathology analysis demonstrated that ipragliflozin might considerably reduce brain damage compared to sepsis and vehicle groups that showed interstitial edema and included glial cells with pyknotic nuclei.
Conclusion: Ipragliflozin attenuates brain dysfunction during CLP-induced polymicrobial sepsis in male mice.
Materials & Methods: Twenty-four adult male Swiss-albino mice aged 8-12 weeks (25-35g) were randomized into four equal groups (n=6): sham (laparotomy without cecal ligation and puncture (CLP), sepsis (laparotomy with CLP), vehicle (equivalent volume of DMSO before CLP), and ipragliflozin (3mg/kg/day, orally before CLP). Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, toll-like receptor 4 (TLR4), and P-signal transducer and activator of transcription (STAT)-3 levels were assessed in the brain tissue and histological examination was done.
Findings: The tissue levels of TNF-α, IL-6, and IL-1B in the sham group were much lower than in the sepsis and vehicle groups. Furthermore, the ipragliflozin group had considerably lower tissue levels of TNF-α, IL-6, and IL-1B compared to the sepsis and vehicle groups. However, the sham group showed much lower tissue levels of TLR4 and STAT3 compared to the sepsis and vehicle groups. Also, the tissue levels of TLR4 and STAT3 in the ipragliflozin group were considerably lower than those in the sepsis and vehicle groups. Histopathology analysis demonstrated that ipragliflozin might considerably reduce brain damage compared to sepsis and vehicle groups that showed interstitial edema and included glial cells with pyknotic nuclei.
Conclusion: Ipragliflozin attenuates brain dysfunction during CLP-induced polymicrobial sepsis in male mice.
Keywords:
References
1. Jawad AS, Hassan ES, Mohammad AR. Protective effect of empagliflozin from acute renal injury during endotoxemia in mice model. Lat Am J Pharm. 2022;41(2):463-71. [Link]
2. Hamza RT, Majeed SA, Ghafil FA, Hassan ES, Hadi NR. Nephroprotective effect of melatonin in sepsis induces renal injury : CLP mice model. Lat Am J Pharm. 2022;41(3):589-96. [Link]
3. Abd Uljaleel A, Hassan E. Protective effect of ertugliflozin against acute lung injury caused by endotoxemia model in mice. Iran J War Public Health 2023;15(1):67-75. [Link]
4. Abd Uljaleel AQ, Hassan ES, Mohammad AR, Hadi NR. Protective effect of dulaglutide on lung injury in endotoxemia mouse model. Iran J War Public Health. 2023;15(1):35-42. [Link]
5. Mohammad AR, Hadi AR, Hassan ES. Potential protective effect of ibrutinib from acute brain injury during endotoxemia in mice. Lat Am J Pharm. 2022;41(2):472-80. [Link]
6. O'Sullivan LA, Liongue C, Lewis RS, Stephenson SE, Ward AC. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol. 2007;44(10):2497-506. [Link] [DOI:10.1016/j.molimm.2006.11.025]
7. Hosoi T, Okuma Y, Kawagishi T, Qi X, Matsuda T, Nomura Y. Bacterial endotoxin induces STAT3 activation in the mouse brain. Brain Res. 2004:1023(1):48-53. [Link] [DOI:10.1016/j.brainres.2004.06.076]
8. Cho ML, Kang JW, Moon YM, Nam HJ, Jhun JY, Heo SB, et al. STAT3 and NF-κB signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. J Immunol. 2006;176(9):5652-61. [Link] [DOI:10.4049/jimmunol.176.9.5652]
9. Hassan ES, Jawad AS, Mohammad AR. Protective effect of liraglutide from acute renal injury during endotoxemia in mice mode. Lat Am J Pharm. 2022;41(2):428-36. [Link]
10. Hussein SN, Majeed SA, Ghafil FA, Hassan ES, Hadi NR. Toll-like receptors 4 antagonist, Ibudilast, ameliorates acute renal impairment induced by sepsis in an experimental model. BNJHS. 2022;140(7):2900-9. [Link]
11. Lee HJ, Shin JS, Lee KG, Park SC, Jang YP, Nam JH, et al. Ethanol extract of potentilla supina linne suppresses LPS‐induced inflammatory responses through NF‐κB and AP‐1 inactivation in macrophages and in endotoxic mice. Phytother Res. 2017;31(3):475-87. [Link] [DOI:10.1002/ptr.5773]
12. Anderberg SB, Luther T, Frithiof R. Physiological aspects of Toll‐like receptor 4 activation in sepsis‐induced acute kidney injury. Acta Physiol. 2017;219(3):575-90. [Link] [DOI:10.1111/apha.12798]
13. Poole RM, Dungo RT. Ipragliflozin: First global approval. Drugs. 2014;74(5):611-7. [Link] [DOI:10.1007/s40265-014-0204-x]
14. Chen J, Williams S, Ho S, Loraine H, Hagan D, Whaley JM, et al. Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members. Diabetes Ther. 2011;1(2):57-92. [Link] [DOI:10.1007/s13300-010-0006-4]
15. Hummel CS, Lu C, Loo DD, Hirayama BA, Voss AA, Wright EM. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol. 2011;300(1):C14-21. [Link] [DOI:10.1152/ajpcell.00388.2010]
16. Ohgaki R, Wei L, Yamada K, Hara T, Kuriyama C, Okuda S, et al. Interaction of the sodium/glucose cotransporter (SGLT) 2 inhibitor canagliflozin with SGLT1 and SGLT2: Inhibition kinetics, sidedness of action, and transporter-associated incorporation accounting for its pharmacodynamic and pharmacokinetic features. J Pharmacol Exp Ther. 2016;358(1):94-102. [Link] [DOI:10.1124/jpet.116.232025]
17. Vallon V. Molecular determinants of renal glucose reabsorption. Focus on "Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2". Am J Physiol Cell Physiol. 2011;300(1):C6-8. [Link] [DOI:10.1152/ajpcell.00444.2010]
18. Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes. 2005;54(12):3427-34. [Link] [DOI:10.2337/diabetes.54.12.3427]
19. Kashiwagi A, Kazuta K, Yoshida S, Nagase I. Randomized, placebo‐controlled, double‐blind glycemic control trial of novel sodium‐dependent glucose cotransporter 2 inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig. 2014;5(4):382-91. [Link] [DOI:10.1111/jdi.12156]
20. Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, et al. Pharmacological profile of ipragliflozin (ASP1941), a novel selective SGLT2 inhibitor, in vitro and in vivo. Naunyn Schmiedebergs Arch Pharmacol. 2012;385:423-36. [Link] [DOI:10.1007/s00210-011-0713-z]
21. Kashiwagi A, Yoshida S, Nakamura I, Kazuta K, Ueyama E, Takahashi H, et al. Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes stratified by body mass index: A subgroup analysis of five randomized clinical trials. J Diabetes Investig. 2016;7(4):544-54. [Link] [DOI:10.1111/jdi.12471]
22. Kashiwagi A, Yoshida S, Kawamuki K, Nakamura I, Kazuta K, Ueyama E. Effects of ipragliflozin, a selective sodium-glucose co-transporter 2 inhibitor, on blood pressure in Japanese patients with type 2 diabetes mellitus: A pooled analysis of six randomized, placebo-controlled clinical trials. Diabetol Int. 2017;8:76-86. [Link] [DOI:10.1007/s13340-016-0283-x]
23. Yokote K, Terauchi Y, Nakamura I, Sugamori H. Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (Stella-elder): Final results of a post-marketing surveillance study. Expert Opin Pharmacother. 2016;17(15):1995-2003. [Link] [DOI:10.1080/14656566.2016.1219341]
24. Maegawa H, Tobe K, Tabuchi H, Nakamura I. Baseline characteristics and interim (3-month) efficacy and safety data from STELLA-LONG TERM, a long-term post-marketing surveillance study of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice. Expert Opin Pharmacother. 2016;17(15):1985-94. [Link] [DOI:10.1080/14656566.2016.1217994]
25. Ishihara H, Yamaguchi S, Nakao I, Okitsu A, Asahina S. Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): A multi-centre, randomized, placebo-controlled, double-blind study. Diabetes Obes Metab. 2016;18:1207-16. [Link] [DOI:10.1111/dom.12745]
26. Drosatos K, Khan RS, Trent CM, Jiang H, Son NH, Blaner WS, et al. Peroxisome proliferator-activated receptor-γ activation prevents sepsis-related cardiac dysfunction and mortality in mice. Circ Heart Fail. 2013;6(3):550-62. [Link] [DOI:10.1161/CIRCHEARTFAILURE.112.000177]
27. Hohlbaum K, Bert B, Dietze S, Palme R, Fink H, Thöne-Reineke C. Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice. PLoS One. 2018;13(9):e0203559. [Link] [DOI:10.1371/journal.pone.0203559]
28. Yousif NG, Hadi NR, Al-Amran FG, Zigam QA. Cardioprotective effects of irbesartan in polymicrobial sepsis. Herz. 2018;43(2):140-5. [Link] [DOI:10.1007/s00059-017-4537-6]
29. Chandrashekhar VM, Ranpariya VL, Ganapaty S, Parashar A, Muchandi AA. Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats. J Ethnopharmacol. 2010;127(3):645-51. [Link] [DOI:10.1016/j.jep.2009.12.009]
30. Pokela M. Predictors of brain injury after experimental hypothermic circulatory arrest: An experimental study using a chronic porcine model. Oulu: OulunREPO; 2003. [Link] [DOI:10.1080/14017430310006956]
31. Weigand MA, Hörner C, Bardenheuer HJ, Bouchon A. The systemic inflammatory response syndrome. Best Pract Res Clin Anaesthesiol. 2004;18(3):455-75. [Link] [DOI:10.1016/j.bpa.2003.12.005]
32. Ebersoldt M, Sharshar T, Annane D. Sepsis-associated delirium. Intensive Care Med. 2007;33:941-50. [Link] [DOI:10.1007/s00134-007-0622-2]
33. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010;304(16):1787-94. [Link] [DOI:10.1001/jama.2010.1553]
34. Sharshar T, Porcher R, Siami S, Rohaut B, Bailly-Salin J, Hopkinson NS, et al. Brainstem responses can predict death and delirium in sedated patients in intensive care unit. Crit Care Med. 2011;39(8):1960-7. [Link] [DOI:10.1097/CCM.0b013e31821b843b]
35. Mina F, Comim CM, Dominguini D, Cassol-Jr OJ, DallIgna DM, Ferreira GK, et al. Il1-β involvement in cognitive impairment after sepsis. Mol Neurobiol. 2014;49:1069-76. [Link] [DOI:10.1007/s12035-013-8581-9]
36. Chen J, Xia H, Zhang L, Zhang H, Wang D, Tao X. Protective effects of melatonin on sepsis-induced liver injury and dysregulation of gluconeogenesis in rats through activating SIRT1/STAT3 pathway. Biomed Pharmacother. 2019;117:109150. [Link] [DOI:10.1016/j.biopha.2019.109150]
37. Zhuo Y, Zhang S, Li C, Yang L, Gao H, Wang X. Resolvin D1 promotes SIRT1 expression to counteract the activation of STAT3 and NF-κB in mice with septic-associated lung injury. Inflammation. 2018;41(5):1762-71. [Link] [DOI:10.1007/s10753-018-0819-2]
38. Tahara A, Kurosaki E, Yokono M, Yamajuku D, Kihara R, Hayashizaki Y, et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur J Pharmacol. 2013;715(1-3):246-55. [Link] [DOI:10.1016/j.ejphar.2013.05.014]
39. Wan S, Jiao X, Cao H, Gu Y, Yan L, Zheng Y, et al. Advances in understanding the innate immune‐associated diabetic kidney disease. FASEB J. 2021;35(2):e21367. [Link] [DOI:10.1096/fj.202002334R]
40. Tahara A, Takasu T. Prevention of progression of diabetic nephropathy by the SGLT2 inhibitor ipragliflozin in uninephrectomized type 2 diabetic mice. Eur J Pharmacol. 2018;830:68-75. [Link] [DOI:10.1016/j.ejphar.2018.04.024]
41. Karimy JK, Reeves BC, Kahle KT. Targeting TLR4-dependent inflammation in post-hemorrhagic brain injury. Expert Opin Ther Targets. 2020;24(6):525-33. [Link] [DOI:10.1080/14728222.2020.1752182]
42. Xue H, Li M. Protective effect of pterostilbene on sepsis-induced acute lung injury in a rat model via the JAK2/STAT3 pathway. Ann Transl Med. 2020;8(21):1452. [Link] [DOI:10.21037/atm-20-5814]
43. Kang Y, Zhan F, He M, Liu Z, Song X. Anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis. Vasc Pharmacol. 2020;133:106779. [Link] [DOI:10.1016/j.vph.2020.106779]
44. Chin KL, Ofori-Asenso R, Hopper I, von Lueder TG, Reid CM, Zoungas S, et al. Potential mechanisms underlying the cardiovascular benefits of sodium glucose cotransporter 2 inhibitors: A systematic review of data from preclinical studies. Cardiovasc Res. 2019;115(2):266-76. [Link] [DOI:10.1093/cvr/cvy295]
45. Altaş M, Meydan SEDAT, Aras M, Yılmaz N, Ulutaş KT, Okuyan HM, et al. Effects of ceftriaxone on ischemia/reperfusion injury in rat brain. J Clin Neurosci. 2013:20(3);457-61. [Link] [DOI:10.1016/j.jocn.2012.05.030]
46. Saw M, Wong VW, Ho IV, Liew G. New anti-hyperglycaemic agents for type 2 diabetes and their effects on diabetic retinopathy. Eye. 2019;33(12):1842-51. [Link] [DOI:10.1038/s41433-019-0494-z]