Akut Enflamasyonlu Tavşanlarda Kortistatin Uygulamasının Antioksidan Sistem ve Sitokin Seviyeleri Üzerine Etkileri

Year 2017, Volume: 7 Issue: 2/2, 190 - 201, 28.12.2017

Banu Atalay

Abstract

Çalışmada,
beyinden izole edilen kortistatin (CST) isimli endojen bir nöropeptidin,
terebentin yağı ile akut enflamasyon oluşturulan tavşanlarda antioksidan sistem
parametreleri ve sitokin düzeyleri üzerine etkilerinin incelenmesi
amaçlanmıştır. Sağlıklı, 28 adet erkek Yeni Zelanda ırkı tavşan kullanılan
araştırmada, hayvanlar kontrol (C), terebentin uygulaması (T), kortistatin
uygulaması (250 µg/kg) (CST) ve terebentin + kortistatin (250 µg/kg) (T+CST)
uygulaması olacak şekilde rastgele dört gruba ayrılmıştır. 2.saatte ve 6.saatte
alınan kan örneklerinden antioksidan ve oksidan sistemlere ait indirgenmiş
glutatyon (GSH), süper oksit dismutaz (SOD) ve malondialdehit (MDA)
düzeylerinin, enflamatuar sitokinlerden ise interlöykin-6 (IL-6) ve tümör
nekrozis faktör -α (TNF-α) seviyelerinin incelendiği araştırmada kortistatin
uygulaması, T+K grubunda GSH seviyesinde T grubuna nazaran anlamlı derecede
koruyucu seviyenin sürdürülmesine katkıda bulunurken (p<0.05), enflamasyonla
birlikte dokuda lipid peroksidasyon düzeyinin artışına bağlı olarak yükselen
MDA seviyesi ve SOD seviyeleri açısından ise istatistiki olarak önemli olmayan
bir değişikliğe yol açmıştır (p>0.05). Çalışmanın sonucunda elde edilen
verilere dayanarak kortistatin, enflamasyonu baskılayıcı bir rol oynadığına
dair etkiler gözlenmesine rağmen, çalışma dizaynı kısa sürdüğü için, bunun
endotoksemi ve sepsis gibi durumlarda gözlenen etkisinden küçük olduğu sonucuna
varılmıştır.

Keywords

kortistatin, antioksidan parametreler, redükte glutatyon, malondialdehit, interlöykin-6

The Effects of Cortistatin Administration on Plasma Antioxidant System and Cytokine Levels of Rabbits with Acute Inflammation

Abstract

In the study, it was aimed to research the effects of an endogenous
neuropeptide called cortistatin (CST) which is isolated from the brain on
parameters of antioxidant system and cytokine levels of rabbits with turpentine
oil induced acute inflammation. In the study using 28 healthy, male rabbits
from New Zealand breed, animals were randomly divided into four groups
consisting of control (C), turpentine (T), cortistatin (250 µg/kg) (CST), and
turpentine + cortistatin (250 µg/kg) (T+CST). Reduced glutathione (GSH), super
oxide dismutase (SOD, malondialdehyde (MDA) levels belonging to antioxidant and
oxidant systems, interleukin-6 (IL-6) and tumor necrosis factor -α (TNF-α)
levels from inflammatory cytokines were studied in the blood samples taken
after 2 and 6 hours and while cortistatin administration significantly
contributed for maintaining GSH at protective level in T+CST group (p<0.05),
it caused a change which was not statistically significant with respect to MDA
and SOD levels increasing based on elevated lipid peroxidation levels in the
tissue along with the inflammation (p>0.05). Depending on resulting data of
the study, it was concluded that despite there were effects observed regarding
that cortistatin plays an inflammation suppressing role, this was smaller than
the effect observed in conditions such as endotoxemia and sepsis because design
of study did not lasted for long.

Keywords

cortistatin, antioxidant parameters, reduced glutathione, malondialdehyde, interleukin-6

References

• Alsemgeest, S.P., Van’t Klooster, G.A., Van Miert, A.S., HulskampKoch, C.K., & Gruys, E. (1996). Primary bovine hepatocytes in the study of cytokine induced acute-phase protein secretion in vitro. Veterinary Immunology and Immunopathology, 53, 179-184.
• Baranowska, B., Chmielowska, M., Wolinska-Witort, E., Bik, W., Baranowska-Bik, A., & Martynska, L. (2006). Direct effect of cortistatin on GH release from cultured pituitary cells in the rat. Neuro Endocrinol Lett, 27 (1-2), 153-156.
• Baumann, H., Held, W.A., & Berger, F.G. (1984). The acute phase response of mouse liver. Genetic analysis of the major acute phase reactants. J Biol Chem, 259, 566–573.
• Broglio, F., Papotti, M., Muccioli, G., & Ghigo, E. (2007). Brain-gut communication: cortistatin, somatostatin and ghrelin. Trends Endocrinol Metab, 18, 246–51.
• Carrasco, E., Herndandez, C., de Torres, I., & al. (2008). Lowered cortistatin expression is an early event in the human diabetic retina and is associated with apoptosis and glial activation. Mol Vis, 14, 1496–502.
• Chiu, C.T., Wen, L.L., Pao, H.P., & Wang, J.Y. (2011). Cortistatin is induced in brain tissue and exerts neuroprotection in a rat model of bacterial meningoencephalitis. J Infect Dis., Nov 15, 204(10), 1563-72.
• de Lecea, L., Criado, J.R., O Prospero-Garcia, K.M., Gautvik, P., Schweitzer, P.E. Danielson & al.(1996). A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature, 381, 242–245.
• Deghenghi, R., Papotti, M., Ghigo, E., & Muccioli, G. (2001). Cortistatin, but not somatostatin, binds to growth hormone secretagogue (GHS) receptors of human pituitary gland. J Endocrinol Invest, 24, RC1–RC3.
• Engler, R. (1995). Acute-phase proteins in inflammation. C R Seances Soc Biol Fil, 189, 563–578.
• Fantuzzi, G.,& Dinarello, C.A. (1996). The inflammatory response in interleukin-1 beta-deficient mice: comparison with other cytokine- related knock-out mice. J Leukoc Biol, 59, 489–493.
• Gabay, C., & Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. N Engl J Med, 340, 448–454.
• Gershenwald, J.E., Fong, Y.M., Fahey, T.J., Calvano, S.E., Chizzonite, R., Kilian, P.L., & al. (1990). Interleukin 1 receptor blockade attenuates the host inflammatory response. Proc Natl Acad Sci USA, 87, 4966–4970.
• Gilroy, D.W., Lawrence, T., Perretti, M., & Rossi, A.G. (2004). Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov, 3, 401–416.
• Gonzales-Rey, E., Chorny, A., Robledo G., & Delgrado, M. (2006). Cortistatin, a new antiinflamatory peptide with therapeutic effect on lethal endotoxemia. The Journal of Experimental Medicine, 203, (3, March 20), 563-571.
• Gonzalez-Rey. E., Chorny. A., Del Moral, R.G., Varela, N., & Delgado, M. (2007). Therapeutic effect of cortistatin on experimental arthritis by downregulating inflammatory and Th1 responses, Ann Rheum Dis, 66, 582–588.
• Gonzalez-Rey, E., Varela, N., Sheibanie, A.F., Chorny, A., Ganea, D., & Delgado, M. (2006). Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease. Proc Natl Acad Sci USA, 103, 4228– 4233.
• Granado, M., Priego, T., Martin, A.I., Villanua, M.A., & Lopez- Calderon, A. (2005). Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am J Physiol Endocrinol Metab, 288, E486–E492.
• Janeway, Jr.C.A., & Medzhitov, R. (2002). Innate immune recognition. Annu Rev Immunol, 20, 197-216.
• Koj, A. (1985). Cytokines regulating acute inflammation and synthesis of acute-phase proteins. Blut, 51, 267–274.
• Labow, M., Shuster, D., Zetterstrom, M., Nunes, P., Terry, R., Cullinan, E.B., & al (1997). Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice. J. Immunol, 159, 2452–2461.
• Lawrence, T., Willoughby, D.A., & Gilroy, D.W. (2002). Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nat Rev Immunol, 2, 787–795.
• Leavy, O. (2006). Cortistatin to the rescue. Nature Reviews, May, 6, 337.
• Leon, L.R., Kozak, W., Peschon, J., & Kluger, M.J. (1997). Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice. Am J Physiol Regulatory Integrative Comp Physiol, 272, R563–R569.
• Marchenko, G.N., & Strongin, A.Y. (2001). MMP-28, a new human matrix metalloproteinase with an unusual cysteine-switch sequence is widely expressed in tumors. Gene; 265, 87–93.
• Morell, M., Souza-Moriera, L., Caro, M., & al.(2013). Analgesic effect of the neuropeptide cortistatin in murine models of arthritic inflammatory pain. Arthritis Rheum, 65, 1390–401.
• Oldenburg, H.S.A., Keller, B., Lazarus, D., Rogy, M.A., Nguyen, L., & Chizzonite, R. (1995). Interleukin-1 binding to its type I, but not type II receptor, modulates the in vivo acute phase response. Cytokine, 7, 510– 516.
• Poznanovic, G., Petrovic, M., & Magic, Z. (1997). Re-establishment of homeostasis and the acute-phase proteins. Panminerva Med, 39, 291– 298.
• Rubinfeld, H., & Shimon, I. (2007). Cortistatine new neuroendocrin hormone?. Pediatr Endocrinol Rev, 2006 Dec-2007 Jan, 4, 2, 106-110.
• Rubio, A., Avila, J., & de Lecea, L. (2007). Cortistatin as a therapeutic target in inflammation. Expert Opin Ther Targets, 11, 1–9.
• Serhan, C.N., Gotlinger, K., Hong, S., & Arita, M. (2004). Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis. Prostaglandins Other Lipid Mediat, 73, 155–172.
• Sheikh, N., Tron, K., Dudas, J., & Ramadori, G. (2006). Cytokine-induced neutrophil chemoattractant-1 is released by the noninjured liver in a rat acute-phase model. Laboratory Investigation, 86, 800–814.
• Sims, J., Gayle, M., Slack, J., Alderson, M., Bird, T., Giri, J., & al (1993). Interleukin 1 signaling occurs exclusively via the type I receptor. Proc Natl Acad Sci USA, 90, 6155–6159.
• Soszynski, D., & Krajewska, M. (2002). Lack of tolerance between pyrogenic effects of LPS and turpentine in rats. J Therm Biol, 27, 229—37.
• Souza-Moreira, L., Campos-Salinas, J., Caro, M., & Gonzales-Rey, E. (2011). Neuropeptides as pleitropic modulators of the immun response. Neuroendocrinology, 94, 89-100.
• Sternberg, E.M. (2006). Neural regulation of innate immünity: a coordinated nonspesific host response to pathogens. Nat Rev Immunol, 6, 318-328.
• Tous, M., Ribas, V., Ferre, N., Escoli-Gil, J.C., Blanco-Vaca, F., Alonso-Villaverde, C., Coll, B., Camps, J., & Joven, J. (2005). Turpentine-induced inflammation reduces the hepatic expression of the multiple drug resistance gene, the plasma cholesterol concentration and the development of atherosclerosis in apolipoprotein E deficient mice. Biochim Biophys Acta, 15, 1733 (2-3), 192-198.
• Viani, P., Cervato, G., Fiorilli, A., & Cestaro, B. (1991). Age related difference in synaptosomal peroxidative damage and membrane properties. J Neurochem, 56, 253-258.
• Wilson, D.N., Chung, H., Elliot, R.C., & al. (2005). Microarray analysis of postictal transcriptional regulation of neuropeptides. J Mol Neurosci, 25, 285–97.
• Yoshioka, M., Watanabe, A., Shimada, N., Murata, H., Yokomise, Y., & Nakajima, Y. (2002). Regulation of haptoglobulin secretion by recombinant bovine cytokines in primary cultured bovine hepatocytes. Domest Anim Endocrinol, 23 (3), 425-33.