Muammer ELMAS, Ayşe ER, Feray ALTAN, Bunyamin TRAS, Kamil UNEY, ÇETİN Gul, Enver YAZAR

Effects of drugs on kinetic values of cytokines, adenosine deaminase and 13,14-dihydro-15-keto-prostaglandin $F_{2alpha}$ in endotoxemia: A different approach

Altan F, Elmas M, Er A, Üney K, Çetin G, Traş B, Yazar E. Endotoksemide ilaçların sitokinler, adenozin deaminaz ve 13,14-dihidro-15-keto-prostaglandin F_{2alpha'nın kinetik değerlerine etkisi: Farklı bir yaklaşım. Eurasian J Vet Sci, 2010, 26, 1, 15-19 Amaç: Lipopolisakkaritle (LPS) oluşturulan deneysel endotoksemide sitokinler, adenozin deaminaz (ADA) ve 13,14-dihidro-15-keto-prostaglandin $F_{2alpha}$ (PGM)’nın kinetik değerlerine tek başlarına ve/veya kombine uygulanan enrofloksasin (ENR), fluniksin meglumin (FM) ve deksametazonun (DEX) etkilerini belirlemektir. Gereç ve Yöntem: Araştırmada kullanılan ratlar 7 gruba ayrıldı. Deneysel endotoksemi oluşturmak için pozitif kontrol grubu dahil bütün gruplara LPS uygulandı. Diğer altı gruba ENR, FM, düşük doz DEX, yüksek doz DEX, ENR+FM+düşük doz DEX ve ENR+FM+yüksek doz DEX uygulandı. Uygulama sonrası 0, 1, 2, 4, 6, 8, 12, 24 ve 48. saatlerde kan örnekleri toplandı. Tümör nekroz faktör alfa ($TNF_{alpha}$), interlökin-6 (IL- 6), interlökin-10 (IL-10), ADA ve PGM düzeyleri ELISA ile belirlendi. Eğri altında kalan alan ($EAA_{0-48}$) farmakokinetik programla, plazma veya serum maksimum konsantrasyon ($C_{max}$) ile maksimum konsantrasyona ulaşma zamanı ($t_{max}$) direk bakı yöntemiyle belirlendi. Bulgular: Pozitif kontrol (LPS) grubuyla kıyaslandığında $EAA_{0-48}$ değerlerinin; ENR grubunda PGM için artarken (p

Endotoksemide ilaçların sitokinler, adenozin deaminaz ve 13,14-dihidro-15-keto-prostaglandin $F_{2alpha}$'nın kinetik değerlerine etkisi: Farklı bir yaklaşım

Altan F, Elmas M, Er A, Uney K, Cetin G, Tras B, Yazar E. Effects of drugs on kinetic values of cytokines, adenosine deaminase and 13,14-dihydro-15-keto-prostaglandin F2a in endotoxemia: A different approach. Eurasian J Vet Sci, 2010, 26, 1, 15-19 Aim: The objective of this study was to determine the effects of enrofloxacin (ENR), flunixin meglumine (FM) and dexamethasone (DEX) on kinetic values of cytokines, adenosine deaminase (ADA) and 13,14-dihydro-15-keto-prostaglandin F2a (PGM) in lipopolysaccharide-induced endotoxemia. Materials and Methods: Rats were divided into seven groups. To induce endotoxemia, lipopolysaccharide (LPS) was injected into all groups, including the positive control. The six other groups received the following drugs: ENR, FM, low-dose DEX, high-dose DEX, ENR + FM + low-dose DEX and ENR + FM + high-dose DEX. After the treatments, blood samples were collected at 0, 1, 2, 4, 6, 8, 12, 24, and 48 hours. Serum tumor necrosis factor alpha ($TNF_{alpha}$), interleukin- 6 (IL-6), interleukin-10 (IL-10), ADA and plasma PGM levels were determined by ELISA. Area under the concentration time curve ($AUC_{0-48}$), maximal concentration in plasma or serum ($C_{max}$) and time to reach ($t_{max}$) values were determined by pharmacokinetic computer program. Results: ENR increased (p

PDF

___

Aldridge AJ, 2002. Pole of the neutrophil in septic shock and the adult respiratory distress syndrome. Eur J Surg, 168, 204-214.
Andreasen AS, Krabbe KS, Krogh-Madsen R, Taudorf S, Pedersen BK, Moller K, 2008. Human endotoxemia as a model of systemic inflammation. Curr Med Chem, 15, 1697-1705.
Basu S, Eriksson M, 2000. Vitamin E in relation to lipid peroxidation in experimental septic shock. Prostag Leukotr Ess, 62, 195-199.
Basu S, Nozari A, Liu XL, Rubertsson S, Wiklund L, 2000. Development of a novel biomarker of free radical damage in reperfusion injury after cardiac arrest. FEBS Letters, 470, 1-6.
Chatterjee S, Premachandran S, Shukla J, Poduval TB, 2007. Synergistic therapeutic potential of dexamethasone and L-arginine in lipopolysaccharide induced septic shock. J Surg Res, 140, 99-108.
Conlon BA, Law WR, 2004. Macrophages are a source of extracellular adenosine deaminase-2 during inflammatory response. Clin Exp Immunol, 138, 14-20.
Dalhoff A, Shalit I, 2003. Immunomodulatory effects of quinolones. Lancet Infect Dis, 3, 359-371.
Elmas M, Yazar E, Baş AL, Traş B, Bayezit M, Yapar K, 2002. Comparative pharmacokinetics of enrofloxacin and tissue concentrations of parent drug and ciprofloxacin after intramuscular administrations of free and liposome-encapsulated enrofloxacin in rabbits. J Vet Med B, 49,507-512.
Elmas M, Uney K, Karabacak A, Yazar E, 2005. Pharmacokinetics of flunixin meglumin following intravenous administration in Angora rabbits. Bull Vet Inst Pulawy, 49, 85-89.
Elmas M, Yazar E, Uney K, Er (Karabacak) A, 2006a. Influence of Escherichia coli endotoxin induced endotoxaemia on the pharmacokinetics on enrofloxacin after intravenous administration in rabbits. J Vet Med A, 53, 410-414.
Elmas E, Yazar E, Uney K, Karabacak A, 2006b. Pharmacokinetics of flunixin after intravenous administration in healthy and endotoxaemic rabbits. Vet Res Commun, 30, 73-81.
Elmas M, Uney K, Yazar E, Karabacak A, Tras B, 2007. Pharmacokinetics of enrofloxacin following intravenous and intramuscular administration in Angora rabbits. Res Vet Sci, 82, 242-245.
Elmas M, Yazar E, Uney K, Er (Karabacak) A, Tras B, 2008. Pharmacokinetics of enrofloxacin and flunixin meglumine and interactions between both drugs after intravenous co-administration in healthy and endotoxaemic rabbits. Vet J, 177, 418-424.
Elmas M, Bulbul A, Avci GE, Er A, Uney K, Yazar E, Tras B, 2009. Effects of enrofloxacin, flunixin meglumine and dexamethasone on disseminated intravascular coagulation and cytokine levels in endotoxemia. J Vet Pharm Ther, 32, 1, 218-219.
Er A, Uney K, Altan F, Cetin G, Yazar E, Elmas M, 2009. Effects of different doses of dexamethasone plus flunixin meglumine on survival rate in lethal endotoxemia. Acta Vet Beograd, 59, 47-51.
Er A, Altan F, Cetin G, Uney K, Tras B, Elmas M, Yazar E, 2010. Effects of Enrofloxacin, Flunixin and Dexamethasone on Indicators of Oxidative and Organ Damage in Lipopolysaccharide-Induced Endotoxemia. J Anim Vet Adv (in press).
Guisti G, 1974. Adenosine deaminase. In: Methods of Enzymatic Analysis, Eds; Bergmeyer H.V., Academic Press, NY, USA, pp: 1092-1099.
Hanada T, Yoshimura A, 2002. Regulation of cytokine signaling and inflammation. Cytokine Growth, 13, 413- 421.
Jean-Baptiste E, 2007. Cellular mechanisms in sepsis. J Intensive Care Med, 22, 63-72.
Keskin E, Oztekin E, Col R, Sivrikaya A, Uney K, Yazar E, 2005. Effect of pentoxifylline on antioxidant status of healthy and endotoxemic New Zealand White rabbits. Acta Vet Brno, 74, 17-21.
Lee CW, Chuang JH, Wang PW, Chang NK, Wang HC, Huang CC, Tiao MM, Lo SK, 2006. Effect of glucocorticoid pretreatment on oxidative liver injury and survival in jaundiced rats with endotoxin cholangitis. World J Surg, 30, 2217-2226.
Macdonald J, Galley HF, Webster NR 2003. Oxidative stress and gene expression in sepsis. Brit J Anaesth, 90, 221-232.
Meduri GU, 1999. An historical review of glucocorticoid treatment in sepsis. Disease pathophysiology and the design of treatment investigation. Sepsis, 3, 21- 38.
Minneci PC, Deans KJ, Banks SM, Eichacker PQ, Natanson C, 2004. Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med, 141, 47-56.
Netea MG, van der Meer JWM, van Deuren M, Kullberg BJ, 2003. Proinflammatory cytokines and sepsis syndrome: not enough, or too much of a good thing? Trends Immunol, 24, 254-258.
Sevransky J, Natanson C, 2000. Clinical trials in sepsis: an update. Curr Opin Anaesthesiol, 13, 125-129.
Smith GW, 2005. Supportive therapy of the toxic cow. Vet Clin Food Anim, 21, 595-614.
Tofovic SP, Zacharia L, Carcillo JA, Jackson EK, 2001. Inhibition of adenosine deaminase attenuates endotoxininduced release of cytokines in vivo in rats. Shock. 16, 196-202.
Wang Z, Kang J, Li Y, Yuan Z, Liu A, Sun L, 2006. The effects of dexamethasone on rat brain cortical nuclear factor kappa B (NF-KB) in endotoxic shock, Toxicol Appl Pharmacol, 214, 263-269.
Yazar E, Konyalioglu S, Col R, Birdane YO, Bas AL, Elmas M, 2004a. Effect of vitamin E and prednisolone on some oxidative stress markers in endotoxemic rabbits. Rev Med Ved, 155, 538-542.
Yazar E, Col R, Konyalioglu S, Birdane YO, Elmas M, Bas AL, 2004b. Effect of vitamin E and prednisolone on biochemical parameters in endotoxaemic New Zealand White rabbits. Bull Vet Ins Pulawy, 48, 105-108.
Yazar E, Er A, Uney K, Altunok V, Elmas M, 2007. Effect of flunixin meglumine on cytokine levels in experimental endotoxemia in mice. J Vet Med A, 54, 352-355.
Yazar E, Er A, Uney K, Bulbul A, Avci GE, Elmas M, Tras B, 2010a. Effects of drugs used in endotoxic shock on oxidative stress and organ damage markers. Free Radic Res, 44, 397-402.
Yazar E, Bulbul A, Avci GE, Er A, Uney K, Elmas M and Tras B, 2010b. Effects of enrofloxacin, flunixin meglumine and dexamethasone on disseminated intravascular coagulation, cytokine levels and adenosine deaminase activity in endotoxaemia in rats. Acta Vet Hung, 58, 357-368.