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Amiodarone May Prevent the Tilmicosin-caused Lethal Toxicity
(UNIV FED RIO GRANDE DO SUL, 2014) Er, Ayse; Tras, Bunyamin; Cetin, Gul; Dik, Burak
Background: Tilmicosin is widely used in veterinary medicine and its accidental overdose by injection may cause death via causing negative inotropy and positive chronotropy in both the treated animal and the veterinarian. In addition, there is no any antidote against to tilmicosin-caused death. Amiodarone blocks some channels in the heart, but it has much complex effect including vagotonic, bradycardic etc on the heart. Considering vagotonic and bradycardic effects of amiodarone, it has been hypothesised that amiodarone may prevent tilmicosin-caused death. The aim of this study was to determine the effect of amiodarone on the survival rate of rats in tilmicosin-caused lethal toxicity. Materials, Methods & Results: Twenty female Wistar rats (body weight: 288 +/- 33.8 g, age: 7-8 months) were used in this study. The study protocol was approved by the Ethical Committee. Rats received food and water ad libitum. The rats were divided into two groups containing 10 rats each. Rats in Group 1 were administered 360 mg/kg of tilmicosin in a single subcutaneous injection. Rats in Group 2 were administered 25 mg/kg of amiodarone via the tail vein at 8. min after the single subcutaneous injection of tilmicosin in a dose of 360 mg/kg. After the injections, deaths were recorded at 0, 2, 6, 10, 12 and 24 h. At the end of the 24-h period, survival/death ratio was analysed by the Chi-square test. The level of statistical significance was set at P < 0.05. The survival rate of Group 2 (40%) was statistically significantly (P < 0.025) higher than that of Group 1 (0.0%). In control group all rats died at 10 h after subcutaneously tilmicosin injection. In Group 2 were administered 25 mg/kg of amiodarone (intravenously) at 8 min after the single subcutaneous injection of tilmicosin in a dose of 360 mg/kg, and 2 rats died at 2 h and 4 rats died at 12 h. At the end of the experiment, all rats died in tilmicosin injected group whereas 4 rats lived in amiodarone and tilmicosin administered group. Clinically tilmicosin administered rats were observed as worse than amiodarone and tilmicosin administered group. Observed clinical signs of toxicity were fluffed feathers, ataxia, weakness in the legs, hypoactivity, lethargy. Discussion: Tilmicosin, a macrolide antibiotic, is widely used in the therapy of respiratory system infections in cattle and sheep. However, tilmicosin has cause serious cardiac side effects, and after tilmicosin administration to animals or accidental self-exposure of this drug to humans, if may cause heart related side effects including chest pain, increased serum cardiac damage markers, changed electrocardiogram, and decreased antioxidant enzyme activities in the heart, serum potassium level and death, as well as. Tilmicosin causes negative inotropy and positive chronotropy. Although the mechanism of tilmicosin-induced cardiotoxicity is not fully known, the inhibitory effect of tilmicosin on the entry of calcium into the cell may cause this lethal effect. It can be speculated that the beneficial effect of amiodarone in tilmicosin toxicity may primarily depend on the potassium channel blocking, antiarrhythmic effect and other exactly not explained effects. Amiodarone may increase survival rate and may be beneficial in the treatment of tilmicosin-caused lethal toxicity. However, especially specific cellular target or other effects of amiodarone on the heart are needed to determine in the tilmicosin toxicity.
ASSESSMENT OF THE CARDIOTOXICITY OF TULATHROMYCIN IN RABBITS
(AKADEMIAI KIADO ZRT, 2011) Er, Ayse; Altan, Feray; Cetin, Gul; Dik, Burak; Elmas, Muammer; Yazar, Enver
The aim of this study was to determine the cardiotoxic potency of tulathromycin. Tulathromycin (10 mg/kg, SC) was administered to ten adult male rabbits, and blood samples were obtained before and after drug administration (0 and 6 hours). Serum cardiac damage markers (troponin I, creatine kinase-MB, myoglobin, lactate dehydrogenase, aspartate aminotransferase), routine serum biochemical values (alkaline phosphatase, alanine aminotransferase, gammaglutamyltransferase, creatinine, blood urea nitrogen, cholesterol, triglyceride, high-density lipoprotein, amylase, total protein, albumin, glucose, calcium, ionised calcium, sodium, potassium), white blood cell (WBC) and red blood cell (RBC) counts, arterial blood gas parameters (pH, partial carbon dioxide pressure, partial oxygen pressure, actual bicarbonate, standard bicarbonate, total carbon dioxide, base excess in vivo, base excess in vitro, oxygen saturation, packed cell volume, haemoglobin) and serum oxidative status (malondialdehyde, nitric oxide, superoxide dismutase, retinol, beta-carotene) were measured. Increased levels of troponin I, creatine kinase-MB and creatinine, and decreased WBC counts, ionised calcium and potassium levels were observed after drug administration. Tulathromycin treatment may cause cardiotoxicity, but its effects may be less dramatic than those of other macrolide antibiotics frequently used in veterinary medicine.
Assessment of the Protective Effects of Pomegranate Peel Extract and N-Acetyl Cysteine Alone or in Combination With Ornipural® Against Cadmium-Induced Bone Toxicity in Rat
(Selçuk Üniversitesi, 2024 Mart) Hatipoğlu, Durmuş; Demircioğlu, İsmail; Filikçi, Kürşat; Korkmaz, Yasemin; Güngör, Hüseyin; Demircioğlu, Muhammed; Dik, Burak
Öz Amaç: Bu çalışma, nar kabuğu ekstresi (PPE) ve N-asetil Sistein (NAC)'in tek başına veya ticari preparat Ornipural® (ORN) ile birlikte kullanımının, deneysel olarak kadmiyum (Cd) indüklenmiş toksisiteye karşı kemik metabolizması üzerindeki etkilerini belirlemek amacıyla yapılmıştır. Gereç ve Yöntem: Çalışmada her grupta 6 adet Wistar Albino sıçan olmak üzere toplam 36 hayvan kullanıldı. Hayvanlar kontrol, Cd, Cd+PPE, Cd+NAC, Cd+PPE+ORN ve Cd+NAC+ORN gruplarına atandı. Gruplardaki hayvanlara 8. haftanın sonunda kan örnekleri alındıktan sonra ötenazi uygulandı. Ötenazi sonrasında morfometrik ve histopatolojik incelemeler için kemikler maserasyona tabi tutuldu. Bulgular: Tedavi grupları ile Cd grubu arasında histopatolojik değişiklikler (osteoporotik değişiklikler ve kırmızı kemik iliğinde değişiklikler) ve biyobelirteçler (Ca, P ve Mg) açısından istatistiksel olarak anlamlı farklılıklar belirlendi (P<0.05). Öneri: Deneysel olarak indüklenmiş kadmiyum toksisitesine karşı uygulanan PPE, NAC ve ORN ile birlikte uygulanan tedavi kombinasyonlarının kemik metabolizması üzerinde olumlu etkilerinin olduğu belirlenmiş olmasına rağmen, uygulanan tedavi protokollerinin kesin etkililiğini belirlemek için tedavi süresini ve dozunu artırarak denemeler yapmanın faydalı olacağı düşünülmüştür.
Cardiac Safety of Diclofenac at a Single Dose in Ram
(HINDAWI LTD, 2013) Er, Ayse; Dik, Burak; Corum, Orhan; Cetin, Gul
Nonsteroidal anti-inflammatory drugs are frequently prescribed drug group in human and veterinary medicine. However, diclofenac, a traditional nonsteroidal anti-inflammatory drug, related to cardiotoxicity is reported, and blood cardiac damage markers may increase within the first hours after damage. The aim of the current research was to determine the effect of diclofenac on the blood cardiac damage markers. Single dose of diclofenac (2.5mg/kg, IM) was injected to 6 rams. Blood samples were collected in before (0 hour, control) and 6 hours after injection. Specific (troponin I, and creatine kinase-MB) and nonspecific (lactate dehydrogenase, aspartate aminotransferase) blood cardiac damage marker concentrations, routine biochemical (hepatic damage, renal damage, lipid metabolism, glucose, and phosphorus) parameters, and hemogram values were measured. Diclofenac increased (P < 0.05) specific (troponin I) and nonspecific cardiac (lactate dehydrogenase, aspartate aminotransferase), hepatic (aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferase), andmuscular (creatine kinase) damagemarkers and high density lipoprotein level, while it decreased (P < 0.05) low density lipoprotein level. Moreover, diclofenac decreased (P < 0.05) white blood cell counts and increased (P < 0.05) red blood cell counts. In conclusion, it may be stated that diclofenac shows slight cardiotoxicity, whereas it may show potent hepatic and muscular damage effects at an intramuscularly single dose in sheep. Thereby, repeated injections of diclofenac may be more harmful in sheep.
Cardiac safety of gamithromycin in ewes
(2016) Corum, Orhan; Dik, Burak; Bahcivan, Emre; Eser, Hatice; Er, Ayse; Yazar, Enver
Amaç: Bir makrolid antibiyotik olan gamitromisin sığırlarda pasteurellosis tedavisinde önerilmekle birlikte koyunlarda etiket dışı olarak kullanılmaktadır. Makrolid antibiyotiklerin kardiyotoksik etkileri bilinmektedir, ancak gamitromisinin koyunlarda kardiyak güvenilirliği ile ilgili bilgi bulunmamaktadır. Araştırmanın öncelikli amacı koyunlarda gamitromisinin kardiyak güvenilirliğini belirlemektir. Bunun yanı sıra karaciğer ve böbrek fonksiyonlarına ve hemogram parametrelerine etkisini tespit etmektir.Gereç ve Yöntem: Araştırmada 10 adet koyuna gamitromisin (6 mg/kg, SC) tek doz olarak uygulandı. Kan örnekleri uygulamadan önce (0. gün, kontrol) ve sonraki 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8 ve 9. günlerde alındı. Spesifik kalp hasar belirteçleri olan serum kreatin kinaz-MB kütle ve troponin I düzeyleri, karaciğer ile böbrek hasar belirteçleri ve hemogram parametreleri ölçüldü. Bulgular: Araştırmada troponin I düzeyinde birinci gün istatistiki olmayan yükselmeler belirlenirken, kreatin kinaz-MB kütle düzeyinde değişimler belirlenmedi. Total bilirubin, total protein, kreatinin ve akyuvar düzeyinde referans değerler arasında istatistiki değişimler belirlendi (P0.05).
A Cardioprotective Role of Nerium oleander with the Expression of Hypoxia Inducible Factor 2A mRNA by Increasing Antioxidant Enzymes in Rat Heart Tissue
(UNIV FED RIO GRANDE DO SUL, 2018) Hitit, Mustafa; Corum, Orhan; Corum, Duygu Durna; Donmez, Huseyin; Cetin, Gul; Dik, Burak; Er, Ayse
Background: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillate intraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes. Materials, Methods & Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 g each) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groups according to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP). Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene. The expression of manganese superoxide dismutase (MnSOD) mRNA was in a steady state level between the control group and group 2 (P > 0.05); however, it significantly increased in group 3 and 4 compared with that in the control (P < 0.05). Expression of catalase (CAT) mRNA was significantly higher in group 2 than in the control group (P < 0.05) although it was lower in group 3 and 4 than in group 2 (P < 0.05); however, it appeared to be similar among the control group, group 3, and group 4 (P > 0.05). Copper (Cu) SOD mRNA was equally expressed in both the control group and group 2 (P > 0.05) but was lower in group 3 and 4 than in group 2 (P < 0.05). Expressions of HIF1A, HIF2A, and HIF3A mRNA were detected in the rat heart tissues in the control and 2, 4, and 8 h after administration of NO distillate. Expression of HIF1A mRNA was in a steady state and did not differ among groups 2, 3, and 4 (P > 0.05). Similarly, the expression of HIF2A mRNA did not change between the control group and group 2 (P > 0.05); however, it was higher in group 3 than in the control (P < 0.05) and tended to be higher in group 3 than in group 2 (P = 0.063). HIF3A mRNA expression did not change significantly in the heart tissue of any of the groups (P > 0.05). Discussion: The present study using rats determined that MnSOD, CAT, CuSOD, HIF1A, HIF2A, and HIF3A mRNA are expressed in the heart tissues after administration of NO distillate. The increased expression of HIF2A mRNA after 4 h in accordance with a rise in CAT mRNA after 2 h, and MnSOD mRNA after 4 and 8 h might confirm the role of HIF2A mRNA in oxidative stress defense by regulating antioxidant enzymes; consequently, this study may expand our understanding of uses of NO distillate with respect to molecular pathways.
Corynebacterium cutis Lysate Treatment Can Increase the Efficacies of PPR Vaccine
(MARY ANN LIEBERT, INC, 2016) Dik, Burak; Dik, Irmak; Bahcivan, Emre; Avci, Oguzhan
This study aimed to evaluate the effects of Peste des petits ruminants (PPR) vaccine on cytokine and antibody levels in sheep when administered alone or in combination with Corynebacterium cutis lysate (CCL). The PPR vaccine group received a single subcutaneous axillary injection of the PPR vaccine (1mL containing tissue culture infectious dose (TCID)(50) attenuated live PPRV, n=6) and the combination treatment (1mL CCL and 1mL PPR vaccine, n=6) groups received a single subcutaneous axillary injection of both CCL and PPR vaccine. Blood samples were collected from sheep before the treatment and at different points after treatment (1, 3, 7, 14, 21, and 28 days). Plasma and serum samples were evaluated for antibody percentage, levels of cytokines IL-6, IL-10, IFN-, IL-4, IL-12, and IL-18, oxidative stress marker Thiobarbituric acid reactive substances, and hematological and biochemical parameters. Maximum protective antibody levels reach 3-4 weeks after vaccine administration. The combination treatment resulted in significant changes in IFN-, IL-4, IL-12, and IL-18 cytokine levels. These changes were not evident when only the PPR vaccine was administered and antibody percentage against PPRV was short term in PPR vaccine group. In conclusion, combined usage of the PPR vaccine with CCL resulted in a heightened cytokine response, leading to improved antibody level against PPR virus. Repeated CCL treatments can lead to earlier vaccine potency, provide protective efficacy for a longer time, and increase passive immunity.
Doksorubisinin neden olduğu organ hasarlarında Nerium oleander distilatının koruyucu etkinliğinin belirlenmesi
(2014) Dik, Burak; Er, Ayşe; Çorum, Orhan
Amaç: Araştırmanın amacı doksorubisinin neden olduğu oksidatif hasar ve diğer yan etkilere Nerium oleander (NO) distilatının etkisini araştırmaktır. Gereç ve Yöntem: NO yaprakları toplandıktan sonra distilasyonu yapılarak liyofilize edildi. Araştırmada 28 adet rat, Kontrol, Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama), NO (1 mg/kg/gün, oral) ve Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama) NO (1 mg/kg/gün, oral) olmak üzere 4 gruba ayrıldı ve uygulamalar 11 gün süresince yapıldı. Son uygulamadan 24 saat sonra anestezi altındaki ratların kalplerinden kan alındı ve hemen ötenazi edildi. Ayrıca kalp, karaciğer ve böbrek organları alınarak homojenize edildi. Organ tiobarbiturik asit türevi reaktif maddeler (TBARS) düzeyleri ELISA, serum biyokimyasal değerleri otoanalizörle ve tam kan değerleri kan hücresi sayım cihazında belirlendi. Bulgular: Doksorubisin grubunun böbrek TBARS değeri NO distilatı grubundan yüksek (P0.05) belirlenirken, Doksorubisin grubunun kalp TBARS değeri Doksorubisin NO distilatı grubundan düşük (P0.05) belirlendi. Doksorubisin uygulamasının kan hücreleri sayıları, hemoglobin ve hematokrit düzeylerini Kontrol grubuna göre düşürdüğü (P0.05), Doksorubisin NO distilatı uygulamasının sadece hematokrit değerini yükselttiği belirlendi. Doksorubisin uygulamasının serum total protein ile albümin düzeylerini Kontrol grubuna göre düşürdüğü (P0.05), Doksorubisin NO distilatı uygulamasının Kontrol grubuna göre aspartat aminotransferaz ile kan üre nitrojen değerlerini yükselttiği (P0.05) ve total protein, albümin ile kreatinin değerlerini düşürdüğü (P0.05) belirlendi. Öneri: Mevcut araştırmada kullanılan NO distilatı düzeyinin, doksorubisinin neden olduğu istenmeyen etkileri engellemede belirgin etkisinin olmadığı ifade edilebilir.
Doksorubisinin neden olduğu organ hasarlarında Nerium oleander distilatının koruyucu etkinliğinin belirlenmesi
(Selçuk Üniversitesi Veterinerlik Fakültesi, 2014) Er, Ayşe; Çorum, Orhan; Dik, Burak
Amaç: Araştırmanın amacı doksorubisinin neden olduğu oksidatif hasar ve diğer yan etkilere Nerium oleander (NO) distilatı- nın etkisini araştırmaktır. Gereç ve Yöntem: NO yaprakları toplandıktan sonra distilasyonu yapılarak liyofilize edildi. Araştırmada 28 adet rat, Kontrol, Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama), NO (1 mg/kg/gün, oral) ve Doksorubisin (3 mg/kg, iki günde bir peritoniçi, 6 uygulama) + NO (1 mg/kg/gün, oral) olmak üzere 4 gruba ayrıldı ve uygulamalar 11 gün süresince yapıldı. Son uygulamadan 24 saat sonra anestezi altındaki ratların kalplerinden kan alındı ve hemen ötenazi edildi. Ayrıca kalp, karaci- ğer ve böbrek organları alınarak homojenize edildi. Organ tiobarbiturik asit türevi reaktif maddeler (TBARS) düzeyleri ELISA, serum biyokimyasal değerleri otoanalizörle ve tam kan değerleri kan hücresi sayım cihazında belirlendi. Bulgular: Doksorubisin grubunun böbrek TBARS değeri NO distilatı grubundan yüksek (P<0.05) belirlenirken, Doksorubisin grubunun kalp TBARS değeri Doksorubisin + NO distilatı grubundan düşük (P<0.05) belirlendi. Doksorubisin uygulaması- nın kan hücreleri sayıları, hemoglobin ve hematokrit düzeylerini Kontrol grubuna göre düşürdüğü (P<0.05), Doksorubisin + NO distilatı uygulamasının sadece hematokrit değerini yükseltti- ği belirlendi. Doksorubisin uygulamasının serum total protein ile albümin düzeylerini Kontrol grubuna göre düşürdüğü (P<0.05), Doksorubisin + NO distilatı uygulamasının Kontrol grubuna göre aspartat aminotransferaz ile kan üre nitrojen değerlerini yükselttiği (P<0.05) ve total protein, albümin ile kreatinin değerlerini düşürdüğü (P<0.05) belirlendi. Öneri: Mevcut araştırmada kullanılan NO distilatı düzeyinin, doksorubisinin neden olduğu istenmeyen etkileri engellemede belirgin etkisinin olmadığı ifade edilebilir.
Effect of Anti-TNF-alpha on the Development of Offspring and Pregnancy Loss During Pregnancy in Rats
(UNIV FED RIO GRANDE DO SUL, 2016) Er, Ayse; Aydin, Ibrahim; Dik, Burak
Background: Etanercept binds soluble tumor necrosis factor-alpha (TNF-alpha) and is classified as pregnancy risk category B. Increase in TNF-alpha level causes preterm labour or miscarriage. Lipopolysaccharides trigger preterm birth and abortion via producing of pro-inflammatory cytokines. Cytokines are divided into two groups as pro-inflammatory and anti-inflammatory. TNF-alpha is a pro-inflammatory cytokine, whereas interleukin (IL)-10 is an anti-inflammatory cytokine. IL-10 predominant in normal pregnancy while TNF-alpha characterize in abortion and recurrent abortion. The aim of this study was to determine the effect of etanercept on the development of offspring and lipopolysaccharide-induced pregnancy loss. Materials, Methods & Results: Twenty-eight female and 7 male Wistar rats (5-6 months old) were used in this study. The rats were fed a standard pelleted diet and tap water ad libitum. After female rats were caged with males for 1 day, the presence of a vaginal plug was designated as day 0 of pregnancy. Twenty-eight pregnant Wistar rats were divided into 4 equal groups, as follows: control (0.3 mL of Normal Saline Solution intravenously on day 10 of pregnancy); etanercept (0.8 mg kg(-1)/day intraperitoneally on days 9 and 10 of pregnancy); lipopolysaccharide (160 mu g kg(-1) intravenously on day 10 of pregnancy); and etanercept + lipopolysaccharide. Blood samples were obtained from the tail vein on day 10 of pregnancy (3 h after lipopolysaccharide administration). All animals were followed during pregnancy. Pregnancy rates and offspring characteristics were determined. TNF-alpha and IL-10 levels were measured using an ELISA reader. Etanercept alone did not have any negative effects, and etanercept did not prevent (P < 0.05) lipopolysaccharide-induced pregnancy loss. Higher TNF-alpha and IL-10 levels were measured (P < 0.05) in the etanercept + lipopolysaccharide group compared to other groups. Discussion: It is well known that use of etanercept does not increase pregnacy loss. In this study, higher pregnancy rates were determined in the control and etanercept groups than the lipopolysaccharide and etanercept + lipopolysaccharide groups. The proportion of fetal deaths in lipopolysaccharide administered pregnant subjects was decreased by the use of anti-TNF-alpha agents. While the concentrations of TNF-alpha are low in the onset of pregnancy period, the concentrations of TNF-alpha increases a peak level during the onset of labour. Embryonic resorption is affected by Th1 cytokines (TNF-alpha and lL-2) and low-dose lipopolysaccharide without any affecting mother survival, and in the early pregnancy term, the implantation area of embryo is enormously sensitive to these molecules. In the current study, etanercept increased the concentration of TNF-alpha and the concentration of IL-10 when compared to the lipopolysaccharide group. IL-10 has a protective role, while TNF-alpha is an abortive factor during pregnancy. Thus, etanercept did not prevent pregnancy loss. This finding may have reflected an insufficient dose of etanercept. Adverse effects did not occur in the offspring of the etanercept or control groups, and there was no difference between the two groups statistically. Adverse pregnancy outcomes such as stillbirth, low birth weight, spontaneous abortion and herediter malformations are not associated with TNF-alpha inhibitors. In conclusion, etanercept does not pose a major teratogenic risk and has no preventive effects with respect to infection-dependent pregnancy loss.
Effect of Corynebacterium cutis Lysate on Serum Oxidative Stress and Plasma Prostaglandin F2 alpha Metabolite Levels
(UNIV FED RIO GRANDE DO SUL, 2014) Er, Ayse; Dik, Burak; Corum, Orhan
Background: The Corynebacterium cutis lysate is commercial product. Unbalance between oxidants and antioxidants cause oxidative stress and lipid peroxidation in the cell. Macrophages phagocytose large pieces of bacteria and synthesize cytokines. In addition to the benefi cial results of the drug have side effects. Since changes in biochemical parameters refl ect structural dysfunction in the organism, monitoring changes of these parameters is a way to keep track of side effects. The aim of this study was to determine the effect of Corynebacterium cutis lysate on serum thiobarbituric acid-reactive substances (TBARS) and plasma 13,14-dihydro-15-keto-prostaglandinF2a (PGM) levels in sheep. Materials, Methods & Results: Six Merino crossbred ewes (aged > 2 years, weight 40-60 kg) were used in this study. The procedures were approved by the Ethics Committee. A dose of 8 mg (0.4 mL) of commercial Corynebacterium cutis lysate was subcutaneously injected to each of the 6 Merino crossbred ewes. Blood specimens were taken from the sheep prior to injection (day 0, control) and after the injection on days 1, 2, 3, and 4. The levels of serum TBARS and plasma PGM were determined using an Enzyme Linked Immunosorbent Assay (ELISA) reader. The values of the hemogram [ white blood cells (WBC), red blood cells (RBC), platelets (PLT), hematocrit (HTC), and hemoglobin (HBG)] were assessed using a blood cell count apparatus. The levels of plasma creatine kinase-MB (CK-MB), serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine, and cholesterol were determined on an autoanalyzer. The data obtained were analyzed using ANOVA and Scheffe's test as a post hoc test (SPSS 19.0). A P < 0.05 value was taken as the cut-off value for statistical signifi cance. An increase (P < 0.05) in the levels of plasma PGM and serum cholesterol was detected when compared to the control samples, but there was no statistically signifi cant (P > 0.05) change in the other parameters. Discussion: The Corynebacterium cutis lysate is a commercial product and used in cattle, newborn calves, sheep, and poultry as an immunostimulant against infections and to increase body resistance in times of stress. Corynebacterium cutis lysate increased (P < 0.05) in plasma PGM and serum cholesterol levels compared to the control group. Detailed studies dealing with the effect of Corynebacterium cutis lysate on PGM and TBARS are not available in the literature. There is a balance between oxidants and antioxidants in the organism. Unbalance between oxidants and antioxidants caused by increased production of oxidizing species leads to oxidative stress and lipid peroxidation in the cells. The levels of TBARS or malondialdehyde are used in order to determine lipid peroxidation. The levels of serum TBARS, malondialdehyde and PGM increased in experimental infection models. Macrophages phagocytose large pieces of bacteria such as Corynebacterium cutis lysate and this case triggers the synthesis of cytokines by macrophages. Cholesterol metabolism may change in infections, and high levels of cholesterol were determined in test subjects after injection of LPS. Lipid metabolism may be affected by stimulants of the immune system, such as Corynebacterium cutis lysate. In conclusion, Corynebacterium cutis lysate has no effect on the oxidative status and number of blood cells and organ (heart, liver and kidney) damage markers in sheep and it may increase plasma PGM level by stimulating the immune system.
Effect of etanercept on cytokines and 13, 14-dihydro-15-keto-prostaglandin F2 alpha concentrations during endotoxemia
(WILEY-BLACKWELL, 2012) Er, Ayşe; Dik, Burak; Altan, Feray; Çetin, Gül; Üney, Kamil; Elmas, Muammer; Yazar, Enver
[Abstract not Available]
The effect of midkine on growth factors and oxidative status in an experimental wound model in diabetic and healthy rats
(CANADIAN SCIENCE PUBLISHING, 2017) Dik, Burak; Bas, Ahmet Levent; Yazihan, Nuray
Wound healing is important for longevity. Midkine is a cytokine involved in controlling tissue repair and new tissue development, and in regulating inflammation. We investigated the effect of midkine on wound healing in rats. In total, 108 Wistar albino rats were used: 12 as healthy and diabetic controls; 96 were split into 4 groups: healthy, saline treated; healthy, midkine (10 ng/kg, 48 h intervals) treated; diabetic, saline treated; and diabetic, midkine treated. Following wound creation, 6 rats per group were euthanized on days 3, 7, 14, and 28; the wounded skin was removed. Levels of epidermal growth factor (EGF), matrix metalloproteinase-8 (MMP-8), transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and thiobarbituric acid reactive substances (TBARS) were measured. MMP-8 and PDGF levels fluctuated in all groups; TGF-beta fluctuated in the diabetic groups and was significantly higher in the HM group than other groups after 14 days. EGF and VEGF levels were increased in the HM group after 3 days. TBARS levels were highest in the diabetic groups. Macroscopically, the midkine-treated groups healed better. Midkine can accelerate wound healing by influencing growth factors and oxidative status in wound tissues.
Effect of single dose dexamethasone (0.1 mg/kg) on white blood cell counts and serum glucose levels in healthy ewes
(2016) Corum, Orhan; Dik, Burak; Er, Ayse
Amaç: Araştırmanın öncelikli amacı sağlıklı koyunlara tek doz deksametazon (0.1 mg/kg, SC) uygulamasının akyuvar sayısı ve serum glikoz düzeyine etkisini belirlemektedir. Ay-rıca deksametazonun diğer bazı hemogram ve serum biyo-kimyasal parametrelere etkisi de değerlendirilmiştir. Gereç ve Yöntem: Araştırmada 8 adet sağlıklı Akkaraman koyuna 0.1 mg/kg (SC, tek doz) dozunda deksametazon uy-gulandı. Uygulamadan önce (0. saat, kontrol) ve sonraki 4, 8, 12, 24, 36, 48 ve 72. saatlerde kan örnekleri alındı. Akyuvar sayısı, alyuvar sayısı, platelet sayısı, hemogram ve hematok-rit değerleri kan hücresi sayım cihazında ölçülürken, serum glikoz, laktat dehidrogenaz, alkalin fosfataz, total bilirubin, alanin aminotransferaz, aspartat aminotransferaz, gamma glutamiltransferaz, total protein, albümin, kan üre nitrojen, kreatinin, kolesterol, trigliserit, yüksek yoğunluklu lipopro-tein ve düşük yoğunluklu lipoprotein düzeyleri otoanalizör-de ölçüldü. Bulgular: Kontrol (0. saat) zamanla karşılaştırıldığında, dek-sametazonun akyuvar sayısı ve serum glikoz düzeyini yük-selttiği (P0.05) belirlendi ve bu yüksek düzeylerin 48 saat süresince devam ettiği gözlendi. Ayrıca total bilirubin, trig-liserit ve kan üre nitrojen düzeylerinde istatistiki değişimler gözlendi, ancak bu değişimlerin referans aralıklar içinde ol-duğu tespit edildi. Öneri: Koyunlara deksametazon uygulamasının akyuvar sa-yısı ve serum glikoz düzeyini yükseltebileceği ve bu yüksek değerlerin 2-3 gün süresince belirlenebileceği ifade edilebilir.
Effects of bcrp and p-gp modulators on the penetration of aflatoxin b1 into the mouse brain
(KAFKAS UNIV, VETERINER FAKULTESI DERGISI, 2017) Tras, Bunyamin; Cetin, Gul; Uney, Kamil; Dik, Burak; Corum, Orhan; Atalay, Sema
This study was conducted to determine whether the plasma and brain concentrations of AFB(1) are affected by the modulation of P-gp and BCRP using zosuquidar (ZQR) and prazosin (PRZ), respectively. In this study, a total of 40 healthy adult male BALB/c mice (32 +/- 3.7 g) were used. The animals were randomly divided into 5 groups, with 8 animals per group. Group 1 was used for method validation. Group 2 (AF) received intraperitoneal AFB1 at a dose of 20 mg/kg of body weight. Groups 3 (AF+PRZ), 4 (AF+ZQR), and 5 (AF+PRZ+ZQR) received 20 mg/kg of AFB(1) intraperitoneally 30 min after the intraperitoneal administration of prazosin (0.3 mg/kg), zosuquidar (25 mg/kg), and prazosin+zosuquidar (0.3 mg/kg prazosin + 25 mg/kg zosuquidar), respectively. Six hours after the administration of AFB(1), blood and brain samples were collected from the animals in Groups 2 to 5. AFB(1) concentrations were determined using an HPLC system with fluorescence detection. Individual and simultaneous administration of prazosin and zosuquidar significantly reduced the brain concentrations of AFB(1) in comparison to a single administration of AFB(1) (P<0.05). The brain/plasma ratio of the AF group was higher than that of the other groups (AF+PRZ, AF+ZQR, and AF+PRZ+ZQR) (P<0.05). Inducers of transmembrane proteins, especially BCRP, can be life saving during acute AFB(1) poisoning.
The Effects of Florfenicol on the Values of Serum Tumor Necrosis Factor-alpha and Other Biochemical Markers in Lipopolysaccharide-Induced Endotoxemia in Brown Trout
(HINDAWI LTD, 2014) Er, Ayse; Dik, Burak
The aim of the present study was to determine the effects of florfenicol on the expected changes in sTNF-alpha.,damagemarkers of the liver and kidney, and the lipid metabolism parameters in endotoxemic brown trout. Ninety-six brown trout were included in this study. After six of the fish were reserved as the control group, the remaining 90 fish were divided equally into 3 groups as follows: LPS ( 2mg/kg, IP), LPS (2mg/kg, IP) + florfenicol (40mg/kg, IM), and florfenicol (40mg/kg, IM). Blood samples were obtained from the tail of the fish at 1.5, 3, 6, 10, and 24 hours. The levels of sTNF-alpha were determined by ELISA and biochemical markers were evaluated with an autoanalyzer. A significant increase was observed in the values of sTNF-alpha in the LPS and LPS + florfenicol groups (P < 0.05). Significant increases were found in the kidney and liver damage determinants in the LPS and LPS + florfenicol groups (P < 0.05). Irregular changes in the lipid metabolism parameters were observed in all the subgroups. In conclusion, florfenicol does not affect the increases of sTNF-alpha caused by LPS and does not prevent liver or kidney damage; at least, it can be said that florfenicol does not have any evident positive effects on the acute endotoxemia of fish.
Investigation of the Effect of Tarantula cubensis Extract on Acute Phase Response
(UNIV FED RIO GRANDE DO SUL, 2016) Corum, Orhan; Er, Ayse; Dik, Burak
Background: Tarantula cubensis alcoholic extract is used to accelerate wound healing and to relieve edema in many animal species. In addition, it may be useful for many infectious diseases. Considering to these effects, it is believe that these effects may be on immune system. Cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma) secreted by immune cells and acute phase proteins (haptoglobin, alpha 1 acid glycoprotein, serum amyloid A) secreted by liver play role in acute phase response. The aim of the present study was to determine the effect of Tarantula cubensis alcoholic extract on cytokine and acute phase protein levels in sheep. Materials, Methods & Results: Tarantula cubensis alcoholic extract (6 mL/sheep, subcutaneously, single dose) was administered to 6 healthy sheep. Blood samples were obtained before (0 h) and after treatments at 2, 4, 8, 12, 24 and 48 h. Then, blood samples were centrifuged to obtain serum samples. Acute phase cytokines such as serum tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma and acute phase proteins such as haptoglobin, alpha 1 acid glycoprotein and serum amyloid-A concentrations were determined with commercially available kits on ELISA reader. Administration of Tarantula cubensis alcoholic extract caused fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10, interferon gamma levels in sheep. In addition, levels of haptoglobin, alpha 1 acid glycoprotein, serum amyloid A showed fluctuations. But, these fluctuations in acute phase cytokines and acute phase proteins were not statistically significant (P > 0.05). Discussion: Tarantula cubensis alcoholic extract, homeopathic medicine, is used trauma, retentio secundinarium, tendinitis, bluetongue, foot and mouth, metritis and arthritis in many animal species including sheep. Cytokines, secreted against various stimulus including infectious diseases, play role in wound healing and in the regulation of the immune system. In current study, administration of Tarantula cubensis alcoholic extract lead to fluctuations in tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interleukin-10 and interferon gamma levels, but these changes were not statistically significant (P > 0.05). Non-statistical fluctuations in cytokines result from inadequate immunological response of sheep against to Tarantula cubensis alcoholic extract. Also, use of molecular analysis techniques may be changed these results. Acute phase proteins are significantly secreted from the liver during the acute phase response. In current study, administration of Tarantula cubensis alcoholic extract in sheep caused non-statistifical fluctuations on haptoglobin, alpha 1 acid glycoprotein and serum amyloid A levels (P > 0.05). Tumor necrosis factor alpha and interleukin-1 beta stimulate synthesis of interleukin-6. Interleukin-6 provides synthesis of acute phase proteins in liver. Non-statistical fluctuations in acute phase proteins result from inadequate stimulus of IL-6. In conclusion, it may be stated that administration of Tarantula cubensis alcoholic extract has no distinctive effect on the acute phase response. However, when Tarantula cubensis alcoholic extract is administered repeated times or other acute phase parameters are evaluated, different results may be observed.
Koçlara deksametazon uygulamasının kan oksidatif durum ve prostaglandin F2? metaboliti düzeyine etkisi
(2016) Er, Ayşe; Çorum, Orhan; Eser, Hatice; Bahçivan, Emre; Dik, Burak; Yazar, Enver
Amaç: Bu araştırmanın öncelikli amacı sağlıklı koçlara deksametazon uygulamasının serum tiyobarbitürik asit reaktif ürünleri (TBARS) ve plazma 13,14-dihidro-15-keto-prostaglandin F2? (PGM) düzeyine etkisini belirlemektir. Ayrıca deksametazonun hemogram ve serum biyokimyasal parametrelere etkisini değerlendirmektir. Gereç ve Yöntem: Araştırmada 10 adet koça derialtı yolla tek sefer 0.5 mg/kg dozda deksametazon uygulandı. Hayvanlardan uygulama öncesi (0. saat, Kontrol grup) ve sonrası 0.25, 0.5, 1, 2, 4, 8, 12 ve 24. saatlerde kan örnekleri alındı. Serum TBARS ve plazma PGM düzeyleri ELISA okuyucusunda belirlendi. Hemogram değerleri kan hücresi sayım cihazında ölçülürken, biyokimyasal parametreler otoanalizörde ölçüldü.Bulgular: Deksametazonun serum TBARS düzeyinde istatistiki olmayan dalgalanmalara neden olduğu belirlenirken, plazma PGM düzeyine etkisinin olmadığı tespit edildi. Akyuvar ve serum glikoz düzeylerinde ise yükselmelere (P0.05) neden olduğu gözlendi Öneri: Deksametazonun sağlıklı koçlarda belirgin düzeyde antioksidan ve anti-PGM etki göstermediği, ancak hastalık durumunda daha farklı etkiler gösterebileceği ifade edilebilir.
Koyunlarda tarantula cubensis alkolik ekstraktının (Theranekron) serum tiyobarbitürik asit reaktif ürünlerine etkisi
(2014) Dik, Burak; Er, Ayşe; Çorum, Orhan
Amaç: Mevcut araştırmanın amacı koyunlarda Tarantula cubensis alkolik ekstraktının serum tiyobarbitürik asit reaktif ürünlerine etkisini değerlendirmektir. Ayrıca hematolojik ve biyokimyasal parametrelere etkilerini değerlendirmektir. Gereç ve Yöntem: Altı adet Akkaraman koyuna tek doz (6 mL/koyun, SC) Tarantula cubensis alkolik ekstraktı uygulandı. Kan örnekleri uygulamadan hemen önce (0 saat, kontrol) ve sonraki 2, 4, 8, 12, 24 ve 48. saatlerde alındı. Serum tiyobarbitürik asit reaktif ürünleri düzeyi ELISA okuyucusunda belirlendi. Biyokimyasal ve hematolojik parametreler sırası ile otoanalizör ve kan hücresi sayım cihazında belirlendi. Bulgular: Tarantula cubensis alkolik ekstraktı koyunlarda serum tiyobarbitürik asit reaktif ürünleri düzeyini belirgin şekilde düşürdü, ancak istatistiki fark belirlenmedi. Ayrıca ekstratın hematolojik ve biyokimyasal parametrelere olumsuz etkisi belirlenmedi. Öneri: Tarantula cubensis alkolik ekstraktının antioksidan etkinlik gösterebileceği ve kısa süreli değerlendirilmesi dikkate alındığında koyunlarda güvenli olabileceği ifade edilebilir.
Koyunlarda Tarantula cubensis alkolik ekstraktının (Theranekron®) serum tiyobarbitürik asit reaktif ürünlerine etkisi
(Selçuk Üniversitesi Veterinerlik Fakültesi, 2014) Er, Ayşe; Çorum, Orhan; Dik, Burak
Amaç: Mevcut araştırmanın amacı koyunlarda Tarantula cubensis alkolik ekstraktının serum tiyobarbitürik asit reaktif ürünlerine etkisini değerlendirmektir. Ayrıca hematolojik ve biyokimyasal parametrelere etkilerini değerlendirmektir. Gereç ve Yöntem: Altı adet Akkaraman koyuna tek doz (6 mL/koyun, SC) Tarantula cubensis alkolik ekstraktı uygulandı. Kan örnekleri uygulamadan hemen önce (0 saat, kontrol) ve sonraki 2, 4, 8, 12, 24 ve 48. saatlerde alındı. Serum tiyobarbitürik asit reaktif ürünleri düzeyi ELISA okuyucusunda belirlendi. Biyokimyasal ve hematolojik parametreler sırası ile otoanalizör ve kan hücresi sayım cihazında belirlendi. Bulgular: Tarantula cubensis alkolik ekstraktı koyunlarda serum tiyobarbitürik asit reaktif ürünleri düzeyini belirgin şekilde düşürdü, ancak istatistiki fark belirlenmedi. Ayrıca ekstratın hematolojik ve biyokimyasal parametrelere olumsuz etkisi belirlenmedi. Öneri: Tarantula cubensis alkolik ekstraktının antioksidan etkinlik gösterebileceği ve kısa süreli değerlendirilmesi dikkate alındığında koyunlarda güvenli olabileceği ifade edilebilir.

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