ARYA Atherosclerosis Journal

Cardiac and renal fibrosis and oxidative stress balance in lipopolysaccharide-induced inflammation in male rats

Document Type : Original Article(s)

Authors

Fereshteh Asgharzadeh 1
Rahimeh Bargi 1
Mahmoud Hosseini 2
Mehdi Farzadnia 3
Majid Khazaei 4

1 PhD Candidate, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Neurocognitive Research Center AND School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Associate Professor, Departments of Pathology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Professor, Neurogenic Inflammation Research Center AND School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

https://doi.org/10.22122/arya.v14i2.1550
Abstract
BACKGROUND: Subclinical inflammation induced by persistent exposure to lipopolysaccharide (LPS) is found in some clinical conditions such as obesity or diabetes. This study aimed to investigate the effect of recurrent LPS exposure on inflammatory markers, oxidative stress balance and cardiac and renal fibrosis in male rats.METHODS: Male Wistar rats were divided into control and LPS-treated. LPS (10 mg/kg/week) was injected intraperitoneally. After 4 weeks, left ventricles and kidneys were homogenized and stained with hematoxylin and eosin (H&E) and Masson trichrome for histological examination. Serum levels of nitrite, interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured and total thiol, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase were evaluated in the heart and kidney homogenates.RESULTS: Serum inflammatory markers were higher in LPS group than control (nitrite: 37.0 ± 2.2 vs. 25.5 ± 1.9 µmol/l; IL-6: 84 ± 3 vs. 98.0 ± 4.4 pg/ml; TNF-α: 75.5 ± 4.9 vs. 85.3 ± 4.7 pg/ml; respectively, P < 0.050). Evaluation of total thiol concentration (heart: 10.0 ± 0.9 vs. 22.5 ± 1.2; kidney: 7.0 ± 0.5 vs. 27.8 ± 3.1 nmol/g tissue, respectively), catalase (heart: 0.18 ± 0.03 vs. 0.66 ± 0.04; kidney: 0.17 ± 0.03 vs. 0.73 ± 0.03, U/g tissue, respectively) and SOD (heart: 8.01 ± 0.70 vs. 12.3 ± 0.4; kidney: 7.02 ± 0.60 vs. 12.0 ± 0.2, U/g tissue, respectively) showed lower levels in LPS-treated group compared to control; while MDA concentration in LPS group was higher than control (P < 0.05). Histopathological examination in LPS-treated group indicated infiltration of inflammatory cells and more collagen deposition in left ventricle wall and kidney compared to control group.CONCLUSION: We concluded that in clinical conditions with chronic LPS, cardiac and renal fibrosis occurs even in absence of preceding tissue injury due to imbalances in oxidative stress.

Keywords

Inflammation, Lipopolysaccharide
Oxidative Stress
Heart
Kidney
  1. Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol 2007; 147(2): 227-35.
  2. Asgharzadeh F, Rouzbahani R, Khazaei M. Chronic low-grade inflammation: Etiology and its effects. J Isfahan Med Sch 2016; 34(379): 408-21.
  3. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007; 56(7): 1761-72.
  4. Shalapour S, Karin M. Immunity, inflammation, and cancer: An eternal fight between good and evil. J Clin Invest 2015; 125(9): 3347-55.
  5. Tahergorabi Z, Khazaei M. The relationship between inflammatory markers, angiogenesis, and obesity. ARYA Atheroscler 2013; 9(4): 247-53.
  6. Burgoyne JR, Mongue-Din H, Eaton P, Shah AM. Redox signaling in cardiac physiology and pathology. Circ Res 2012; 111(8): 1091-106.
  7. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985) 2005; 98(4): 1154-62.
  8. Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev 2010; 31(6): 817-44.
  9. Shen J, Obin MS, Zhao L. The gut microbiota, obesity and insulin resistance. Mol Aspects Med 2013; 34(1): 39-58.
  10. Tahergorabi Z, Khazaei M, Moodi M, Chamani E. From obesity to cancer: A review on proposed mechanisms. Cell Biochem Funct 2016; 34(8): 533-45.
  11. Sallam N, Khazaei M, Laher I. Effect of moderate-intensity exercise on plasma C-reactive protein and aortic endothelial function in type 2 diabetic mice. Mediators Inflamm 2010; 2010: 149678.
  12. Beutler B, Rietschel ET. Innate immune sensing and its roots: The story of endotoxin. Nat Rev Immunol 2003; 3(2): 169-76.
  13. Frantz S, Kobzik L, Kim YD, Fukazawa R, Medzhitov R, Lee RT, et al. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 1999; 104(3): 271-80.
  14. Court O, Kumar A, Parrillo JE, Kumar A. Clinical review: Myocardial depression in sepsis and septic shock. Crit Care 2002; 6(6): 500-8.
  15. Krishnagopalan S, Kumar A, Parrillo JE, Kumar A. Myocardial dysfunction in the patient with sepsis. Curr Opin Crit Care 2002; 8(5): 376-88.
  16. Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J Clin Invest 2009; 119(10): 2868-78.
  17. Lew WY, Bayna E, Molle ED, Dalton ND, Lai NC, Bhargava V, et al. Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice. PLoS One 2013; 8(4): e61057.
  18. Lew WY, Bayna E, Dalle Molle E, Contu R, Condorelli G, Tang T. Myocardial fibrosis induced by exposure to subclinical lipopolysaccharide is associated with decreased miR-29c and enhanced NOX2 expression in mice. PLoS One 2014; 9(9): e107556.
  19. Elmi S, Sallam NA, Rahman MM, Teng X, Hunter AL, Moien-Afshari F, et al. Sulfaphenazole treatment restores endothelium-dependent vasodilation in diabetic mice. Vascul Pharmacol 2008; 48(1): 1-8.
  20. Khazaei M, Fallahzadeh AR, Sharifi MR, Afsharmoghaddam N, Javanmard SH, Salehi E. Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats. Clinics (Sao Paulo) 2011; 66(8): 1419-24.
  21. Nematollahi S, Nematbakhsh M, Haghjooyjavanmard S, Khazaei M, Salehi M. Inducible nitric oxide synthase modulates angiogenesis in ischemic hindlimb of rat. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2009; 153(2): 125-9.
  22. Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 1990; 9(6): 515-40.
  23. Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci 2005; 8(3): 394-9.
  24. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.
  25. Warren HS, Fitting C, Hoff E, Adib-Conquy M, Beasley-Topliffe L, Tesini B, et al. Resilience to bacterial infection: Difference between species could be due to proteins in serum. J Infect Dis 2010; 201(2): 223-32.
  26. Copeland S, Warren HS, Lowry SF, Calvano SE, Remick D. Acute inflammatory response to endotoxin in mice and humans. Clin Diagn Lab Immunol 2005; 12(1): 60-7.
  27. Seki E, De Minicis S, Osterreicher CH, Kluwe J, Osawa Y, Brenner DA, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 2007; 13(11): 1324-32.
  28. Pulskens WP, Rampanelli E, Teske GJ, Butter LM, Claessen N, Luirink IK, et al. TLR4 promotes fibrosis but attenuates tubular damage in progressive renal injury. J Am Soc Nephrol 2010; 21(8): 1299-308.
  29. Blyszczuk P, Kania G, Dieterle T, Marty RR, Valaperti A, Berthonneche C, et al. Myeloid differentiation factor-88/interleukin-1 signaling controls cardiac fibrosis and heart failure progression in inflammatory dilated cardiomyopathy. Circ Res 2009; 105(9): 912-20.
  30. Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci 2014; 71(4): 549-74.
  31. Weber KT, Sun Y, Bhattacharya SK, Ahokas RA, Gerling IC. Myofibroblast-mediated mechanisms of pathological remodelling of the heart. Nat Rev Cardiol 2013; 10(1): 15-26.
  32. Looi YH, Grieve DJ, Siva A, Walker SJ, Anilkumar N, Cave AC, et al. Involvement of Nox2 NADPH oxidase in adverse cardiac remodeling after myocardial infarction. Hypertension 2008; 51(2): 319-25.
ARYA Atherosclerosis Journal
Volume 14, Issue 2 - Serial Number 2
March and April 2018
Pages 71-77

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us