Evaluation the cardiopulmonary markers in cecal ligation and puncture induced sepsis in Wistar rats

  • Tina Didari Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
  • Shokoufeh Hassani Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
  • Maryam Baeeri Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
  • Vida Kazemi Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Mohammad Abdollahi Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • Mojtaba Mojtahedzadeh Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Objective: Sepsis is a clinical problem caused by host immune disability against pathogens. Rodent Cecal Ligation and Puncture (CLP) models mimic sepsis in humans. Gauges needle size in CLP is related to cytokine storm, inflammation, and organ failure. This study focus, for the first time, on precise and inexpensive biochemical markers to evaluate the difference of sepsis severity in the heart and lung tissues, one day after cecal ligation and puncture-induced sepsis with needle gauge 18 (G-18).
Methods: Twelve adult male Wistar rats were randomly allocated into two groups of 6 animals. These groups include; sham operation as the control group and underwent CLP procedure with G-18. All rats were sacrificed 24 hours after CLP then lungs and heart samples were collected for biochemical and histological assessment. Following the procedure, reactive oxygen species (ROS), Myeloperoxidase Activity (MPO), Tumor Necrosis Factor-Alpha (TNF-α), High Mobility Group Box 1 (HMGB1), lactate generation, caspases (-3 and -9), gene expression of autophagy and cellular hypoxia and pathological assessment of both tissues were measured.
Results: Increased level of ROS, MPO, pro-inflammatory cytokines, hyperlactatemia, caspases production, overexpression of hypoxia (PRKAA1 gene), and autophagy (MAP1LC3B gene) in the lungs were higher compared to heart 24 hours after the procedure. Moreover, hyperplasia of pneumocyte and inflammatory cells, and myocardial necrosis were found in the pathological assessment.
Conclusion: The purpose of  study was to determine the severity of sepsis by means of cost effective and precise inflammatory markers. Our findings demonstrated that injury-related indicators in lungs meaningfully increased compared to heart 24 hours after CLP.
share this Article by

References

1. Drosatos K, Lymperopoulos A, Kennel PJ, Pollak N, Schulze PC, Goldberg IJ. Pathophysiology of sepsis-related cardiac dysfunction: driven by inflammation, energy mismanagement, or both? Current heart failure reports. 2015;12(2):130-40.
2. Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. The New England journal of medicine. 2017;376(23):2235-44.
3. Sun Y, Cai Y, Zang QS. Cardiac Autophagy in Sepsis. Cells. 2019;8(2).
4. Gonzalez MA, Ochoa CD. Multiorgan System Failure in Sepsis. Sepsis: Springer; 2018. p. 67-71.
5. Park I, Kim M, Choe K, Song E, Seo H, Hwang Y, et al. Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury. The European respiratory journal. 2019;53(3).
6. Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. Immunodesign of experimental sepsis by cecal ligation and puncture. Nature protocols. 2008;4(1):31.
7. Dejager L, Pinheiro I, Dejonckheere E, Libert C. Cecal ligation and puncture: the gold standard model for polymicrobial sepsis? Trends in microbiology. 2011;19(4):198-208.
8. Li L, Tan J, Miao Y, Lei P, Zhang Q. ROS and Autophagy: Interactions and Molecular Regulatory Mechanisms. Cellular and molecular neurobiology. 2015;35(5):615-21.
9. Aoki H, Kondo Y, Aldape K, Yamamoto A, Iwado E, Yokoyama T, et al. Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3. Autophagy. 2008;4(4):467-75.
10. Faubert B, Boily G, Izreig S, Griss T, Samborska B, Dong Z, et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo. Cell metabolism. 2013;17(1):113-24.
11. Wichterman KA, Baue AE, Chaudry IH. Sepsis and septic shock--a review of laboratory models and a proposal. The Journal of surgical research. 1980;29(2):189-201.
12. Ebong S, Call D, Nemzek J, Bolgos G, Newcomb D, Remick D. Immunopathologic alterations in murine models of sepsis of increasing severity. Infection and immunity. 1999;67(12):6603-10.
13. Zapelini PH, Rezin GT, Cardoso MR, Ritter C, Klamt F, Moreira JC, et al. Antioxidant treatment reverses mitochondrial dysfunction in a sepsis animal model. Mitochondrion. 2008;8(3):211-8.
14. Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984;87(6):1344-50.
15. Rahimifard M, Navaei-Nigjeh M, Baeeri M, Maqbool F, Abdollahi M. Multiple protective mechanisms of alpha-lipoic acid in oxidation, apoptosis and inflammation against hydrogen peroxide induced toxicity in human lymphocytes. Molecular and cellular biochemistry. 2015;403(1-2):179-86.
16. Baeeri M, Momtaz S, Navaei-Nigjeh M, Niaz K, Rahimifard M, Ghasemi-Niri SF, et al. Molecular evidence on the protective effect of ellagic acid on phosalone-induced senescence in rat embryonic fibroblast cells. Food and chemical toxicology. 2017;100:8-23.
17. Husain-Syed F, McCullough PA, Birk HW, Renker M, Brocca A, Seeger W, et al. Cardio-Pulmonary-Renal Interactions: A Multidisciplinary Approach. Journal of the American College of Cardiology. 2015;65(22):2433-48.
18. Goto M, Samonte V, Ravindranath T, Sayeed MM, Gamelli RL. Burn injury exacerbates hemodynamic and metabolic responses in rats with polymicrobial sepsis. Journal of burn care & research : official publication of the American Burn Association. 2006;27(1):50-9.
19. Liu H, Wu J, Yao JY, Wang H, Li ST. The Role of Oxidative Stress in Decreased Acetylcholinesterase Activity at the Neuromuscular Junction of the Diaphragm during Sepsis. Oxidative medicine and cellular longevity. 2017;2017:1-6.
20. Sener G, Sehirli O, Cetinel S, Ercan F, Yuksel M, Gedik N, et al. Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast. Prostaglandins, leukotrienes, and essential fatty acids. 2005;73(6):453-62.
21. Sener G, Toklu H, Ercan F, Erkanli G. Protective effect of beta-glucan against oxidative organ injury in a rat model of sepsis. Int Immunopharmacol. 2005;5(9):1387-96.
22. Sener G, Toklu H, Kapucu C, Ercan F, Erkanli G, Kacmaz A, et al. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg Today. 2005;35(1):52-9.
23. Xiao X, Yang M, Sun D, Sun S. Curcumin protects against sepsis-induced acute lung injury in rats. The Journal of surgical research. 2012;176(1):e31-9.
24. Chen HH, Lin KC, Wallace CG, Chen YT, Yang CC, Leu S, et al. Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury. Journal of pineal research. 2014;57(1):16-32.
25. Zhu W, Lu Q, Wan L, Feng J, Chen HW. Sodium tanshinone II A sulfonate ameliorates microcirculatory disturbance of small intestine by attenuating the production of reactie oxygen species in rats with sepsis. Chinese journal of integrative medicine. 2016;22(10):745-51.
26. Gonzalez AS, Elguero ME, Finocchietto P, Holod S, Romorini L, Miriuka SG, et al. Abnormal mitochondrial fusion-fission balance contributes to the progression of experimental sepsis. Free radical research. 2014;48(7):769-83.
27. Wang P, Huang J, Li Y, Chang R, Wu H, Lin J, et al. Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats. International journal of molecular sciences. 2015;16(9):20595-608.
28. Liaw WJ, Chen TH, Lai ZZ, Chen SJ, Chen A, Tzao C, et al. Effects of a membrane-permeable radical scavenger, Tempol, on intraperitoneal sepsis-induced organ injury in rats. Shock. 2005;23(1):88-96.
29. Tsao CM, Jhang JG, Chen SJ, Ka SM, Wu TC, Liaw WJ, et al. Adjuvant potential of selegiline in attenuating organ dysfunction in septic rats with peritonitis. PLoS One. 2014;9(9):1-9.
30. Yang S, Zhou M, Chaudry IH, Wang P. Novel approach to prevent the transition from the hyperdynamic phase to the hypodynamic phase of sepsis: role of adrenomedullin and adrenomedullin binding protein-1. Annals of surgery. 2002;236(5):625-33.
31. Zhai X, Yang Z, Zheng G, Yu T, Wang P, Liu X, et al. Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model. Mediators Inflamm. 2018;2018:1-9.
32. Abdulmahdi W, Patel D, Rabadi MM, Azar T, Jules E, Lipphardt M, et al. HMGB1 redox during sepsis. Redox biology. 2017;13:600-7.
33. Léger T, Charrier A, Moreau C, Hininger-Favier I, Mourmoura E, Rigaudière JP, et al. Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status. Physiological Reports. 2017;5(13):1-12.
34. Stevens NE, Chapman MJ, Fraser CK, Kuchel TR, Hayball JD, Diener KR. Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes. Scientific reports. 2017;7(1):1-14.
35. Lin WJ, Yeh WC. Implication of Toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock. 2005;24(3):206-9.
36. Chang CL, Leu S, Sung HC, Zhen YY, Cho CL, Chen A, et al. Impact of apoptotic adipose-derived mesenchymal stem cells on attenuating organ damage and reducing mortality in rat sepsis syndrome induced by cecal puncture and ligation. Journal of translational medicine. 2012;10:1-14.
37. Olguner CG, Koca U, Altekin E, Ergur BU, Duru S, Girgin P, et al. Ischemic preconditioning attenuates lipid peroxidation and apoptosis in the cecal ligation and puncture model of sepsis. Experimental and therapeutic medicine. 2013;5(6):1581-8.
38. Zhou J, Chen Y, Huang GQ, Li J, Wu GM, Liu L, et al. Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture. The Journal of surgical research. 2012;178(1):390-400.
39. Escobar DA, Botero-Quintero AM, Kautza BC, Luciano J, Loughran P, Darwiche S, et al. Adenosine monophosphate-activated protein kinase activation protects against sepsis-induced organ injury and inflammation. The Journal of surgical research. 2015;194(1):262-72.
40. Nishida K, Kyoi S, Yamaguchi O, Sadoshima J, Otsu K. The role of autophagy in the heart. Cell death and differentiation. 2009;16(1):31-8.
41. Zaha VG, Young LH. AMP-activated protein kinase regulation and biological actions in the heart. Circulation research. 2012;111(6):800-14.
42. Mizumura K, Cloonan S, Choi ME, Hashimoto S, Nakahira K, Ryter SW, et al. Autophagy: friend or foe in lung disease? Annals of the American Thoracic Society. 2016;13(Supplement 1):S40-S7.
43. Mungai PT, Waypa GB, Jairaman A, Prakriya M, Dokic D, Ball MK, et al. Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels. Mol Cell Biol. 2011;31(17):3531-45.
44. Hsieh CH, Pai PY, Hsueh HW, Yuan SS, Hsieh YC. Complete induction of autophagy is essential for cardioprotection in sepsis. Annals of surgery. 2011;253(6):1190-200.
45. Lee S, Lee SJ, Coronata AA, Fredenburgh LE, Chung SW, Perrella MA, et al. Carbon monoxide confers protection in sepsis by enhancing beclin 1-dependent autophagy and phagocytosis. Antioxidants & redox signaling. 2014;20(3):432-42.
46. Watanabe E, Muenzer JT, Hawkins WG, Davis CG, Dixon DJ, McDunn JE, et al. Sepsis induces extensive autophagic vacuolization in hepatocytes: a clinical and laboratory-based study. Laboratory investigation; a journal of technical methods and pathology. 2009;89(5):549-61.
47. Takahashi W, Hatano H, Hirasawa H, Oda S. Protective role of autophagy in mouse cecal ligation and puncture-induced sepsis model. Critical Care. 2013;17(2):1-13.
Published
2020-10-26
How to Cite
DIDARI, Tina et al. Evaluation the cardiopulmonary markers in cecal ligation and puncture induced sepsis in Wistar rats. Journal of Contemporary Medical Sciences, [S.l.], v. 6, n. 5, oct. 2020. ISSN 2413-0516. Available at: <http://www.jocms.org/index.php/jcms/article/view/864>. Date accessed: 25 nov. 2020. doi: https://doi.org/10.22317/jcms.v6i5.864.

Most read articles by the same author(s)