Sepsis is a systemic inflammatory consequence resulting from microbial infection, assessed as a worldwide healthcare issue. Sepsis can result in multiorgan dysfunction, including cardiac, renal, hepatic, and cerebral dysfunction. Cardiotoxicity can occur in humans and rodents during sepsis, leading to increased mortality. The current study aims to explore the possible cardioprotective effects of octreotide during sepsis-induced cardiotoxicity. This study was done with a total of forty male albino Swiss mice, aged 8-12 weeks and weighing 25-30 gm. These animals had free access to food and water. After two weeks of adaptation, mice were divided into four groups (n=10): 1) Normal group: healthy mice; 2) CLP group: mice underwent CLP operation; 3) Vehicle group: mice received DMSO. 4) Octreotide group: mice received octreotide (10 mg/kg) subcutaneously in 2 divided doses for 5 consecutive days. All groups underwent CLP operation on the 4th day, then sacrificed on the 5th day then blood, and tissue sampling was done. The Octreotide group demonstrated a significant (P<0.05) decrease in the myocardial levels of cardiac troponin-I as compared to the CLP group. Furthermore, the octreotide group demonstrated a significant (P<0.05) decrease in the serum level of inflammatory cytokines (TNF-α, IL-6, & IL-1β) as compared to the CLP group. Additionally, the octreotide group showed a significant (P<0.05) elevation in the myocardial activity of SOD and a reduction in MDA level compared to the CLP group. Histologically, all mice in the CLP group showed a significant (P<0.05) cardiac tissue injury, while the octreotide groups showed a significant (P<0.05) reduced level of cardiac tissue injury. The results of the present study revealed that octreotide attenuates sepsis-induced cardiotoxicity through different protective effects; they include the anti-inflammatory effect through their ability to decrease serum levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6). Also, the anti-oxidant effect through their ability to decrease myocardial levels of MDA and increase the myocardial activity of SOD. Additionally, the direct cardiac protective effect through the lower level of cardiac troponin- I and the reduction of histopathological changes during sepsis-induced cardiotoxicity. |
- 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? Curr Heart Fail Rep. 2015;12(2):130-40.
- Yousif NG, Hadi NR, Al-Amran F, Zigam QA. Cardioprotective effects of irbesartan in polymicrobial sepsis : The role of the p38MAPK/NF-κB signaling pathway. Herz. 2018;43(2):140-5.
- Napolitano LM. Sepsis 2018: Definitions and Guideline Changes. Surg Infect. 2018;19(2):117-25.
- Angus DC, van der Poll T. Severe Sepsis and Septic Shock. 2013;369(9):840-51.
- Lagu T, Rothberg MB, Shieh MS, Pekow PS, Steingrub JS, Lindenauer PK. Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007. Crit Care Med. 2012;40(3):754-61.
- Fattahi F, Ward PA. Complement and sepsis-induced heart dysfunction. Mol Immunol. 2017;84:57-64.
- Merx MW, Weber C. Sepsis and the Heart. Circulation. 2007;116(7):793-802.
- Martin L, Derwall M, Thiemermann C, Schürholz T. [Heart in sepsis : Molecular mechanisms, diagnosis and therapy of septic cardiomyopathy]. Anaesthesist. 2017;66(7):479-90.
- Lv X, Wang H. Pathophysiology of sepsis-induced myocardial dysfunction. Mil Med Res. 2016;3:30-.
- Tsolaki V, Makris D, Mantzarlis K, Zakynthinos E. Sepsis-Induced Cardiomyopathy: Oxidative Implications in the Initiation and Resolution of the Damage. Oxid Med Cell Longev. 2017;2017:7393525-.
- Hochstadt A, Meroz Y, Landesberg G. Myocardial dysfunction in severe sepsis and septic shock: more questions than answers? J Cardiothorac Vasc Anesth. 2011;25(3):526-35.
- Anthony L, Freda PU. From somatostatin to octreotide LAR: evolution of a somatostatin analogue. Curr Med Res Opin. 2009;25(12):2989-99.
- Hofland LJ, Lamberts SW. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev. 2003;24(1):28-47.
- Cozzi R, Attanasio R, metabolism. Octreotide for acromegaly. Expert Rev Endocrinol Metab. 2007;2(2):129-45.
- Sener G, Cetinel S, Erkanli G, Gedik N, Yeğen BC. Octreotide ameliorates sepsis-induced pelvic inflammation in female rats by a neutrophil-dependent mechanism. Peptides. 2005;26(3):493-9.
- Wen H. Sepsis induced by cecal ligation and puncture. Methods Mol Biol. 2013;1031:117-24.
- Coldewey SM, Rogazzo M, Collino M, Patel NS, Thiemermann C. Inhibition of IκB kinase reduces the multiple organ dysfunction caused by sepsis in the mouse. Dis Model Mech. 2013;6(4):1031-42.
- Bodzon-Kulakowska A, Bierczynska-Krzysik A, Dylag T, Drabik A, Suder P, Noga M, et al. Methods for samples preparation in proteomic research. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;849(1-2):1-31.
- Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47(3):469-74.
- Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302-10.
- Le-Buu Pham T, Thi-Phuong Nguyen D, Thi-Kieu Nguyen O, Thanh Nguyen T, Van Pham P. Mouse model for myocardial injury caused by ischemia. Biomed Res Ther. 2015;1(5):23.
- Zingarelli B, Salzman AL, Szabó C. Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. Circ Res. 1998;83(1):85-94.
- Altmann DR, Korte W, Maeder MT, Fehr T, Haager P, Rickli H, et al. Elevated cardiac troponin I in sepsis and septic shock: no evidence for thrombus associated myocardial necrosis. PloS One. 2010;5(2):e9017.
- Xiping Z, Hua T, Hanqing C, Li C, Zhiwei W, Keyi W, et al. The Protecting Effects and Mechanisms of Baicalin and Octreotide on Heart Injury in Rats with SAP. Mediators Inflamm. 2007;2007:019469.
- Lundberg AH, Granger DN, Russell J, Sabek O, Henry J, Gaber L, et al. Quantitative measurement of P-and E-selectin adhesion molecules in acute pancreatitis: correlation with distant organ injury. Ann Surg. 2000;231(2):213.
- Schaalan MF, Nassar NN. Effects of octreotide in chronically mild stressed rats: possible role of immune and oxidative stress pathways. Neurochem Res. 2011;36(10):1717-23.
- Ma K, Zhang H, Baloch Z. Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review. Int J Mol Sci. 2016;17(5).
- Gomaa RS, Mahmoud NM, Mohammed NA. Octreotide (somatostatin analog) attenuates cardiac ischemia/reperfusion injury via activating nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in rat model of hyperthyroidism. Future J Pharm Sci. 2020;6(1):105.
- Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5(1):9-19.
- Gul M, Seydanoglu A, Ayan M, Cander B, Erayman I, Girisgin S. Dose-dependent effects of octreotide on plasma activities of IL-6 and lung tissue levels of malondialdehyde in sepsis. Crit Care. 2007;11(2):P12.
- Antonucci E, Fiaccadori E, Donadello K, Taccone FS, Franchi F, Scolletta S. Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care. 2014;29(4):500-11.
- Galley HF. Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth. 2011;107(1):57-64.
- Hobai IA, Edgecomb J, LaBarge K, Colucci WS. Dysregulation of intracellular calcium transporters in animal models of sepsis-induced cardiomyopathy. Shock. 2015;43(1):3-15.
34. Lowes DA, Webster NR, Murphy MP, Galley HF. Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis. Br J Anaesth. 2013;110(3):472-80.
|