Nuray Yazihan - Academia.edu (original) (raw)
Papers by Nuray Yazihan
Amaç: Hepatosellüler karsinom dünyada beflinci s›rada en s›k görülen, ciddi bir sa¤l›k sorunudur.... more Amaç: Hepatosellüler karsinom dünyada beflinci s›rada en s›k görülen, ciddi bir sa¤l›k sorunudur. HCC insidans›n›n da¤›l›-m›ndaki farkl›l›k, muhtemelen risk faktörlerine farkl› oranlarda maruz kalmaya ba¤l›d›r. Geliflmekte olan ülkelerde kronik hepatit B virüs enfeksiyonu ve aflatoksin, geliflmifl ülkelerde ise sigara ve alkol kullan›m› önemli risk faktörleridir. Aflatoksin, Hepatosellüler karsinom patogenezinde rol oynayan en önemli çevresel toksinlerden biridir. Yüksek aflatoksin düzeyleri, ülkemizde üretilen besin maddelerinde de gösterilmifltir. Bu çal›fl-man›n amac› sa¤l›kl› kontrol grubu, farkl› viral hepatitler ve hastal›¤›n farkl› derecelerinde aflatoksin düzeylerinin karfl›lafl-t›r›larak, aflatoksin maruziyet oranlar› ve aflatoksin metabo-lizmas› hakk›nda baz› ipuçlar›n›n elde edilmesidir. Yöntem: Çal›flmaya Ankara Üniversitesi T›p Fakültesi Gastroenteroloji Klini¤ine Ocak 2006 -Haziran 2007 tarihleri aras›nda ard›fl›k olarak baflvuran toplam 203 (erkek/kad›n: 119/84) viral hepatitli hasta dahil edildi. Normal biyokimyasal de¤erleri ve negatif serolojisi olan 62 sa¤l›kl› birey (erkek/kad›n:33/29) kontrol grubu olarak çal›flmaya dahil edildi. Plazma AFB1, AFB2, AFG1 ve AFG2 düzeyleri High-performance liquid chromatography yöntemiyle ölçüldü. Bulgular: AFB1, AFB2, AFG1 ve AFG2 s›rayla hastalar›n %24.6, %17.2, %22.7, %18.2' sinde saptand›. Hastal›¤›n derecesinden ba¤›ms›z olarak AFB1 pozitif hastalar›n yüzdesi, kontrol grubundan anlaml› olarak fazla idi. Ancak aflatoksin pozitif hasta yüzdesi aç›s›ndan kronik hepatit, siroz ve hepatosellüler kanserli hasta gruplar› aras›nda analamal› farkl›l›k saptanmad›. Sonuç: Bu çal›flma ile Türkiye'de viral hepatitli hastalarda aflatoksin maruziyetinin, sa¤-l›kl› kontrol grubuna göre anlaml› olarak fazla oldu¤u gösterildi. Hepatosellüler karsinom gelifliminde bu maruziyetin önemli rolü olabilir ve bu konuda yap›lacak daha genifl, randomize çal›flmalar gerekmektedir. Anahtar kelimeler: Aflatoksin, viral hepatit, kronik hepatit, siroz, hepatosellüler karsinom Background/aims: Hepatocellular carcinoma is the fifth most common cancer and a major public health problem worldwide. Differences in distribution of hepatocellular carcinoma incidence are probably due to different levels of exposure to hepatocellular carcinoma risk factors: chronic infections with hepatitis B virus (HBV) and aflatoxin exposure in developing countries, and smoking and alcohol abuse in developed countries. Aflatoxin is one of the most important of the environmental toxins that contribute to the pathogenesis of hepatocellular carcinoma, especially in the regions where dietary foodstuffs (peanuts, corn, Brazil nuts, pistachios, spices and figs) are highly contaminated. High aflatoxin levels have been shown in the foodstuffs that are produced in our country. The specific aim of this study was to assess the rate of aflatoxin exposure and to determine some clues about aflatoxin metabolism by measuring and comparing the levels of carcinogenic forms in healthy subjects, in different stages of viral disease, and in different viral hepatitis types. Methods: This was a cross-sectional observational, single-center study. A total of 203 (male/female: 119/84) viral hepatitis patients who were consecutively admitted to were enrolled into the study. Sixty-two healthy subjects (male/female: 33/29) with normal blood chemistry and negative viral serology served as controls. Chemical forms AFB1, AFB2, AFG1, and AFG2 were assessed in plasma of study participants by high-performance liquid chromatography. Results: AFB1, AFB2, AFG1, and AFG2 were detected in 24.6%, 17.2%, 22.7%, 18.2% of the 203 patients, respectively, and were significantly higher than in the control group for all chemical forms. Percentage of AFB1-positive patients was significantly higher than in the control group irrespective of disease stage. There was no significant difference between chronic infected patients, cirrhotic patients and patients with Hepatocellular carcinoma with respect to percentage of aflatoxin-positive individuals. Conclusions: With this study, we have documented that in viral hepatitis patients, aflatoxin exposure is significantly higher than in healthy subjects in Turkey and it may play an important role in the development of hepatocellular carcinoma. Thus, large studies exploring the relation between aflatoxin exposure, viral hepatitis status, and risk of hepatocellular carcinoma development are needed.
The Open Drug Discovery Journal, 2010
Ischemia and/or reperfusion injury (IR) is one of the most common causes of acute renal failure. ... more Ischemia and/or reperfusion injury (IR) is one of the most common causes of acute renal failure. Erythropoietin (EPO), is main hematopoietic hormone that has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental I/R and toxicity models.
Journal of Investigative Surgery, 2008
ATP dependent K channels (K-ATP) take part in the Erythropoietin (EPO) induced cardioprotection b... more ATP dependent K channels (K-ATP) take part in the Erythropoietin (EPO) induced cardioprotection but these channel activations have role in cytoprotective role of EPO in the renal ischemia reperfusion (IR) damage is still unknown. For this purpose rats were pretreated with EPO (500 IU/kg) and/or K-ATP channel blocker glibenclamide (40 mM/kg) i.p. before bilateral renal IR damage. Renal tissues were used for histological examination and measurement of caspase-3 and TNF-alpha levels. Renal functions were evaluated by glomerular filtration rate (GFR) fractional excretion of sodium (FENa) and potassium (FEK). Renal TNF-alpha and caspase-3 levels were decreased in both glibenclamide and EPO-treated IR rats compared to untreated rats. The protection afforded by the pretreatment with EPO alone was greater than that of administering glibenclamide alone. Application of glibenclamide at the same time partly abolished the cytoprotective effect of EPO treatment. K-ATP mediated cytoprotection is not the main mechanism of protective effect of EPO.
trma ve E itim Hastanesi, Gastroenteroloji Klini i, ANKARA ÖZET Kronik pankreatit tansnda feka... more trma ve E itim Hastanesi, Gastroenteroloji Klini i, ANKARA ÖZET Kronik pankreatit tansnda fekal elastazn klinik önemi Kronik pankreatitte pankreas ekzokrin fonksiyonlarnn de erlendirilmesi hastal n tan ve tedavisinde önemlidir. Günümüzde ara trmaclar kronik pankreatit tans için invaziv olmayan, tansal do rulu u yüksek, rutin çal maya uygun yeni testler ara trmaya yönelmi tir. Fekal pankreatik elastaz-1 (FE-1) pankreatik ekzokrin fonksiyonla-rn de erlendirilmesinde kullanlabilecek noninvaziv bir yöntem olarak orta ve ciddi pankreatik ekzokrin fonksi-yonlarnn tansna imkan vermektedir. Bu çal mada amacmz, gastroenteroloji klini inde ultrasonografi, bilgi-sayarl tomografi, endoskopik retrograd kolonjiyo pankreotografi ile kronik pankreatit tans alm hastalarda non-invaziv pankreas ekzokrin fonksiyonunun göstergesi olarak FE-1 düzeyinin klinik önemini belirlemek, mikro ELISA yöntemi ile belirlenen FE-1 de erleri için en uygun cut-off de erini tespit etmek, yöntemin sensitivite ve spesifitesini belirlemek, tedavi amaçl enzim preperat kullanan kronik pankreatitli hastalarda FE-1 testinin tansal do rulu unu göstermek, kronik pankreatitli hastalarda FE-1 düzeyleri ile serum lipaz düzeyleri arasndaki korelasyonu ara trmaktr. Çal mamz kronik pankreatit tans alan 26 hasta ile 17 sa lkl ki i olu turdu. Kronik pankreatit tans alm hastalarda sa lkl kontrol grubuna göre fekal elastaz-1 düzeyleri dü ük bulundu (p<0,001). FE-1 yöntemi için cut off de eri 240 µg/g olarak bulundu. Yöntemin sensitivite ve spesifitesi sras ile %92,3 ve %70 idi. Tedavi amaçl enzim preparat kullanan kronik pankreatitli hastalarda enzim preparat kullanmayan kronik pankreatitli hastalara göre FE-1 düzeyinde anlaml bir fark bulunamad (p=0,091). Kronik pankreatitli hasta grubunda FE-1 ile lipaz düzeyleri arasnda korelasyon bulunamad (p=0,836). Sonuç olarak Fekal Elastaz-1 testinin, tansal parametre de erlerinin dü ük bulunmasndan dolay kronik pankreatit tansnda destekleyici bir parametre olabilece i, ancak tansal do ruluk için daha çok vakalarla yaplan çal malara ihtiyaç olabilece i ve enzim preparatlarndan etkilenmemesi nedeniyle, bu amaçla kullanlan test parametreleri arasnda bir avantaja sahip oldu u görü üne varld.
Human & Experimental Toxicology, 2011
Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. C... more Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. Cd, which can induce a broad spectrum of biological effects, is a toxic substance and is associated with inflammation and apoptosis. Midkine (MK) has fibrinolytic, antiapoptotic, transforming, angiogenetic and chemotactic activities. After Cd toxicity, we found increased MK expression in liver cells in an in vitro cell culture model. The aim of this study was to determine the possibility of relationship between tissue MK expression levels, tumor necrosis factor α(TNF-α) levels and apoptosis in a chronic Cd toxicity model in rats. Male Wistar rats were exposed to Cd at the dose of 15 parts per million (ppm) for 8 weeks. MK levels were measured in kidney, heart and liver tissue by enzyme-linked-immunosorbent assay (ELISA). MK messenger RNA (mRNA) expression was evaluated by RT-PCR. Tissue apoptosis level was evaluated with tissue caspase-3 activity levels. Accumulation of Cd in liver is higher than the kidney and heart. Cd-treated rats had significantly higher tissue TNF-α and caspase-3 levels when compared with the control rats (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). MK mRNA and protein levels were also significantly upregulated in the Cd-treated group (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, respectively). When compared with apoptosis in tissues, it was more prominent in the liver than kidney and heart. MK level is found increased 3, 1.7 and 1.3× folds in liver, kidney and heart, respectively. Our results showed that chronic Cd administration induces inflammation and apoptosis in rat liver, kidney and heart. MK involved in damage mechanisms of Cd-induced tissues. Further studies will show the underlying mechanism of increased MK expression in Cd toxicity.
Pathophysiology of Haemostasis and Thrombosis, 2011
Cadmium (Cd) is a heavy metal which affects many systems in humans and animals as a consequence o... more Cadmium (Cd) is a heavy metal which affects many systems in humans and animals as a consequence of environmental and industrial pollution. The aim of this study was to investigate the effect of chronic Cd toxicity on blood pressure and plasma viscosity. Experimental group rats were given doses that contained 15 ppm CdCl(2) in drinking water for 8 weeks. The systolic blood pressure and heart rate were measured from rats&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; tails and recorded by plethysmography every two weeks. Blood samples were drawn, Cd levels were determined by atomic absorption spectrophotometer and plasma viscosity values by viscometer. Blood Cd levels were found to be significantly higher in the experimental group compared to the control group (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The whole blood analysis was made by an analyzer. Polymorphonuclear leukocytes and monocytes increased (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and lymphocyte number (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) decreased in the experimental group. Viscosity values were 2.21 ± 0.54 and 1.62 ± 0.31 centipoises in the experimental and control groups, respectively (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In the experimental group, changes in systolic blood pressure between weeks were significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and were found to be correlated with plasma viscosity (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In the experimental group, changes in heart rate between weeks were significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). According to our findings, Cd toxicity may lead to an increase in blood pressure by increasing plasma viscosity.
Journal of Physiology and Biochemistry, 2004
Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemi... more Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-α level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-α, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 μg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-α levels, and PCs were significantly higher in the I/R group than those in the control group (p<0.05). The administration of leptin decreased these parameters (p<0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p<0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p<0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-α levels and increasing nitrite level. El factor de necrosis tumoral alfa (TNF-α) está implicado en la lesión renal tras isquemia y reperfusión (I/R). Dado que se ha observado que la leptina presenta un efecto citoprotector sobre el tejido renal, se estudia en este trabajo el efecto de la hormona sobre el contenido en el tejido renal de TNF-α, malondialdehido (MDA), niveles de grupos carbonilo protéicos (PC) y de los grupos sulfhidrilo total (SH), y el nivel plasmático de nitrito tras lesión renal por isquemia/reperfusión en rata. Los animales se repartían en tres grupos de 8 ejemplares: control, I/R, e I/R+leptina. Las ratas se sometían a una isquemia renal durante 45 minutos con ulterior reperfusión de una hora. A los del grupo I/R+leptina se les había administrado por vía intraperitoneal leptina (10 μg/kg) 30 minutos antes de la inducción de la isquemia. Los resultados indican que el contenido en MDA, TNF-α y PC está significativamente elevado en el grupo I/R respecto del grupo de control (p<0.05), mientras que el de SH se reduce tras la lesión I/R y el nivel de nitrito en el plasma no varía. El tratamiento con leptina anula los incrementos de los niveles renales de TNF-α, MDA y PC y de la disminución de grupos SH en tejido renal e incrementa el nivel de nitritos plasmáticos por isquemia/reperfusión renal. Estos resultados sugieren que la leptina ejerce un efecto protector sobre la lesión renal inducida por isquemia y reperfusión por la disminución de TNF-α y el aumento plasmático de nitrito.
Journal of Health Science, 2004
Currently, erythropoietin (EPO) treatment in anemic patients is getting more interest, but in lon... more Currently, erythropoietin (EPO) treatment in anemic patients is getting more interest, but in long term, development of hypertension is common problem in EPO treated patients. Since it isn't yet known whether EPO affects directly vascular and/or kidney functions, we aimed to study effects of acute EPO treatment on renal tissue nitrite level, and cardiovascular function and glomerular filtration rate (GFR). Experiments were done under 4 groups. Group I: Sham operated control, group II: 150 IU/kg EPO, group III: 50 mg/kg Nw-nitro-L-arginine methyl ester (L-NAME), group IV: L-NAME+EPO. Femoral artery, vein and bladder were catheterized under anesthesia. After stabilization and first 45 min basal control period, drugs were given i.v. bolus infusion according to the group protocols, then 2 × 45 min clearance periods were followed. EPO infusion increased renal tissue nitrite activity causing GFR increase without any influence on systemic blood pressure. L-NAME alone or together with EPO significantly raised the systemic blood pressure with a partial increase in GFR, but L-NAME treatment significantly reduced tissue nitrite level. The present study for the first time suggests that exogenous EPO treatment increases rat GFR and renal tissue nitrite level without affecting systemic blood pressure.
Journal of Neuro-oncology, 2010
The aim of this work is to investigate whether clomipramine (CIM) and lithium chloride (LiCl) pot... more The aim of this work is to investigate whether clomipramine (CIM) and lithium chloride (LiCl) potentiate the cytotoxicity of vinorelbine (VNR) on SH-SY5Y human neuroblastoma cells in vitro and whether midkine (MK) can be a resistance factor for these treatments. Four groups of experiments were performed for 96 h using both monolayer and spheroid cultures of SH-SY5Y cells: (1) control group, (2) singly applied VNR, CIM, and LiCl, (3) VNR with CIM, and (4) VNR with LiCl. Their effects on monolayer and spheroid cultures were determined by evaluating cell proliferation, bromodeoxyuridine labeling index (BrdU-LI), apoptosis, cyclic adenosine monophosphate (cAMP) and midkine levels, colony-forming efficiency, spheroid size, and ultrastructure. In comparison with the control group, single and combination drug treatments significantly reduced the proliferation index (PI) for 96 h. The most potent reduction of PI was observed with VNR in combination with CIM and LiCl for all time intervals. VNR with CIM and LiCl seemed to be ineffective in reducing BrdU-LI of both monolayer cell and spheroid cultures, spheroid size, and cAMP level. VNR with LiCl increased apoptosis at 24 h, however VNR with CIM increased apoptosis at 96 h. VNR was the most potent drug in inhibiting colony-forming efficiency. The combination of VNR with CIM was the most potent in reducing midkine levels among all groups. Interestingly, the combination of VNR with LiCl led to both nuclear membrane breakdown and disappearance of the cellular membranes inside the spheroids. Both CIM and LiCl seemed to potentiate VNR-induced cytotoxicity, and MK was not a resistance factor for VNR, LiCl, and CIM.
Journal of Physiology and Biochemistry, 2004
Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemi... more Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-α level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-α, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 μg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-α levels, and PCs were significantly higher in the I/R group than those in the control group (p<0.05). The administration of leptin decreased these parameters (p<0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p<0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p<0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-α levels and increasing nitrite level. El factor de necrosis tumoral alfa (TNF-α) está implicado en la lesión renal tras isquemia y reperfusión (I/R). Dado que se ha observado que la leptina presenta un efecto citoprotector sobre el tejido renal, se estudia en este trabajo el efecto de la hormona sobre el contenido en el tejido renal de TNF-α, malondialdehido (MDA), niveles de grupos carbonilo protéicos (PC) y de los grupos sulfhidrilo total (SH), y el nivel plasmático de nitrito tras lesión renal por isquemia/reperfusión en rata. Los animales se repartían en tres grupos de 8 ejemplares: control, I/R, e I/R+leptina. Las ratas se sometían a una isquemia renal durante 45 minutos con ulterior reperfusión de una hora. A los del grupo I/R+leptina se les había administrado por vía intraperitoneal leptina (10 μg/kg) 30 minutos antes de la inducción de la isquemia. Los resultados indican que el contenido en MDA, TNF-α y PC está significativamente elevado en el grupo I/R respecto del grupo de control (p<0.05), mientras que el de SH se reduce tras la lesión I/R y el nivel de nitrito en el plasma no varía. El tratamiento con leptina anula los incrementos de los niveles renales de TNF-α, MDA y PC y de la disminución de grupos SH en tejido renal e incrementa el nivel de nitritos plasmáticos por isquemia/reperfusión renal. Estos resultados sugieren que la leptina ejerce un efecto protector sobre la lesión renal inducida por isquemia y reperfusión por la disminución de TNF-α y el aumento plasmático de nitrito.
Injury-international Journal of The Care of The Injured, 2008
Spinal cord injury (SCI) is a very destructive process for both patients and society. Lipid perox... more Spinal cord injury (SCI) is a very destructive process for both patients and society. Lipid peroxidation is the main cause of the further secondary damage which starts after mechanical destruction of tissues. Recent studies have shown that erythropoietin (EPO) has neuroprotective properties. In this study, we aimed to see the effect of EPO treatment after spinal cord injury on the oxidant and antioxidant enzyme systems and the relationship with the N-methyl-D-Aspartate (NMDA) blockage. Spinal cord injury was produced by epidural compression with a cerebral vascular clip that has a closing force of 40 g for 30 s after a limited multilevel laminectomy (T9-11). Experiment was done in 5 groups: Group1: Sham-operated untraumatised, Group 2: SCI untreated, Group 3: 150 i.u./kg EPO injected i.p. at the end of the first hour following the trauma. Group 4: NMDA receptor antagonist ketamine (100 mg/kg) i.p. Group 5: EPO + ketamine i.p. The experiments were finished after 12 h of the trauma. The spinal cords were excised for biochemical examinations.
Journal of Physiological Sciences, 2006
There is enough evidence that erythropoietin (EPO) may be involved in cardiovascular function. Th... more There is enough evidence that erythropoietin (EPO) may be involved in cardiovascular function. Therefore we have investigated the possible effects of EPO on left ventricular developed pressure, +dP/dt(max), heart rate, tissue cAMP, and nitrite levels. Isolated rat hearts were perfused under constant flow (10 ml/min) conditions with modified Krebs-Henseleit solution and recombinant human erythropoietin at doses of 100, 200, 500, and 1,000 IU/kg was administered as bolus injections. EPO at 100 IU/kg decreased, but higher doses (500 and 1,000 IU/kg) raised the developed pressure and +dP/dt(max). However, it did not affect heart rate or coronary perfusion pressure when all the respective doses were applied. EPO at 100 IU/kg increased nitrite, and at 1,000 IU/kg it raised cAMP. Our results suggest that EPO may produce dose-dependently negative and positive inotropic effects on myocardial contractility in isolated rat hearts. NO and cAMP may be involved in negative and positive inotropic effects of EPO, respectively.
Advances in Therapy, 2008
Introduction Erythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat a... more Introduction Erythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat anaemia in patients on dialysis. In addition, EPO has been shown to have anti-inflammatory properties, which may be important as dialysis patients tend to exist within a chronic, low-grade inflammatory state, and tend to be more susceptible to infections. It has been suggested that EPO has direct immunomodulatory potency on monocytes/macrophages. Methods In this study, we aimed to clarify the effects of EPO during the inflammatory processes in human mononuclear phagocytic cells by monitoring the secretion of the following cytokines; midkine, tumour necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). For this purpose, U937 human histiocytic lymphoma cell lines were used. Time-dependent effects of varying doses of EPO (0.1 to 50 IU/ml) treatment during lipopolysaccharide (LPS)-mediated cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide test. LPS-stimulated midkine secretion was measured immunohistochemically and quantification of TNF-α, IL-6 and midkine secretion was achieved by ELISA. Results EPO treatment prevented the direct toxic effects of LPS on the U937 cells. TNF-α, IL-6 and midkine secretions were found to increase in the U937 cells in response to LPS treatment. Interleukin-6 response was varied in a doseand time-dependent manner. Conclusion Treatment with EPO significantly inhibits the LPS-induced secretion of midkine and TNF-α regardless of the dosage. The data presented here provide the first evidence to indicate that EPO treatment directly reverses some of the cytotoxic and secretory effects of LPS in mononuclear cells. Inhibition of midkine secretion might be responsible for the anti-inflammatory role of EPO.
Amaç: Hepatosellüler karsinom dünyada beflinci s›rada en s›k görülen, ciddi bir sa¤l›k sorunudur.... more Amaç: Hepatosellüler karsinom dünyada beflinci s›rada en s›k görülen, ciddi bir sa¤l›k sorunudur. HCC insidans›n›n da¤›l›-m›ndaki farkl›l›k, muhtemelen risk faktörlerine farkl› oranlarda maruz kalmaya ba¤l›d›r. Geliflmekte olan ülkelerde kronik hepatit B virüs enfeksiyonu ve aflatoksin, geliflmifl ülkelerde ise sigara ve alkol kullan›m› önemli risk faktörleridir. Aflatoksin, Hepatosellüler karsinom patogenezinde rol oynayan en önemli çevresel toksinlerden biridir. Yüksek aflatoksin düzeyleri, ülkemizde üretilen besin maddelerinde de gösterilmifltir. Bu çal›fl-man›n amac› sa¤l›kl› kontrol grubu, farkl› viral hepatitler ve hastal›¤›n farkl› derecelerinde aflatoksin düzeylerinin karfl›lafl-t›r›larak, aflatoksin maruziyet oranlar› ve aflatoksin metabo-lizmas› hakk›nda baz› ipuçlar›n›n elde edilmesidir. Yöntem: Çal›flmaya Ankara Üniversitesi T›p Fakültesi Gastroenteroloji Klini¤ine Ocak 2006 -Haziran 2007 tarihleri aras›nda ard›fl›k olarak baflvuran toplam 203 (erkek/kad›n: 119/84) viral hepatitli hasta dahil edildi. Normal biyokimyasal de¤erleri ve negatif serolojisi olan 62 sa¤l›kl› birey (erkek/kad›n:33/29) kontrol grubu olarak çal›flmaya dahil edildi. Plazma AFB1, AFB2, AFG1 ve AFG2 düzeyleri High-performance liquid chromatography yöntemiyle ölçüldü. Bulgular: AFB1, AFB2, AFG1 ve AFG2 s›rayla hastalar›n %24.6, %17.2, %22.7, %18.2' sinde saptand›. Hastal›¤›n derecesinden ba¤›ms›z olarak AFB1 pozitif hastalar›n yüzdesi, kontrol grubundan anlaml› olarak fazla idi. Ancak aflatoksin pozitif hasta yüzdesi aç›s›ndan kronik hepatit, siroz ve hepatosellüler kanserli hasta gruplar› aras›nda analamal› farkl›l›k saptanmad›. Sonuç: Bu çal›flma ile Türkiye'de viral hepatitli hastalarda aflatoksin maruziyetinin, sa¤-l›kl› kontrol grubuna göre anlaml› olarak fazla oldu¤u gösterildi. Hepatosellüler karsinom gelifliminde bu maruziyetin önemli rolü olabilir ve bu konuda yap›lacak daha genifl, randomize çal›flmalar gerekmektedir. Anahtar kelimeler: Aflatoksin, viral hepatit, kronik hepatit, siroz, hepatosellüler karsinom Background/aims: Hepatocellular carcinoma is the fifth most common cancer and a major public health problem worldwide. Differences in distribution of hepatocellular carcinoma incidence are probably due to different levels of exposure to hepatocellular carcinoma risk factors: chronic infections with hepatitis B virus (HBV) and aflatoxin exposure in developing countries, and smoking and alcohol abuse in developed countries. Aflatoxin is one of the most important of the environmental toxins that contribute to the pathogenesis of hepatocellular carcinoma, especially in the regions where dietary foodstuffs (peanuts, corn, Brazil nuts, pistachios, spices and figs) are highly contaminated. High aflatoxin levels have been shown in the foodstuffs that are produced in our country. The specific aim of this study was to assess the rate of aflatoxin exposure and to determine some clues about aflatoxin metabolism by measuring and comparing the levels of carcinogenic forms in healthy subjects, in different stages of viral disease, and in different viral hepatitis types. Methods: This was a cross-sectional observational, single-center study. A total of 203 (male/female: 119/84) viral hepatitis patients who were consecutively admitted to were enrolled into the study. Sixty-two healthy subjects (male/female: 33/29) with normal blood chemistry and negative viral serology served as controls. Chemical forms AFB1, AFB2, AFG1, and AFG2 were assessed in plasma of study participants by high-performance liquid chromatography. Results: AFB1, AFB2, AFG1, and AFG2 were detected in 24.6%, 17.2%, 22.7%, 18.2% of the 203 patients, respectively, and were significantly higher than in the control group for all chemical forms. Percentage of AFB1-positive patients was significantly higher than in the control group irrespective of disease stage. There was no significant difference between chronic infected patients, cirrhotic patients and patients with Hepatocellular carcinoma with respect to percentage of aflatoxin-positive individuals. Conclusions: With this study, we have documented that in viral hepatitis patients, aflatoxin exposure is significantly higher than in healthy subjects in Turkey and it may play an important role in the development of hepatocellular carcinoma. Thus, large studies exploring the relation between aflatoxin exposure, viral hepatitis status, and risk of hepatocellular carcinoma development are needed.
The Open Drug Discovery Journal, 2010
Ischemia and/or reperfusion injury (IR) is one of the most common causes of acute renal failure. ... more Ischemia and/or reperfusion injury (IR) is one of the most common causes of acute renal failure. Erythropoietin (EPO), is main hematopoietic hormone that has recently been shown to exert important cytoprotective and anti-apoptotic effects in experimental I/R and toxicity models.
Journal of Investigative Surgery, 2008
ATP dependent K channels (K-ATP) take part in the Erythropoietin (EPO) induced cardioprotection b... more ATP dependent K channels (K-ATP) take part in the Erythropoietin (EPO) induced cardioprotection but these channel activations have role in cytoprotective role of EPO in the renal ischemia reperfusion (IR) damage is still unknown. For this purpose rats were pretreated with EPO (500 IU/kg) and/or K-ATP channel blocker glibenclamide (40 mM/kg) i.p. before bilateral renal IR damage. Renal tissues were used for histological examination and measurement of caspase-3 and TNF-alpha levels. Renal functions were evaluated by glomerular filtration rate (GFR) fractional excretion of sodium (FENa) and potassium (FEK). Renal TNF-alpha and caspase-3 levels were decreased in both glibenclamide and EPO-treated IR rats compared to untreated rats. The protection afforded by the pretreatment with EPO alone was greater than that of administering glibenclamide alone. Application of glibenclamide at the same time partly abolished the cytoprotective effect of EPO treatment. K-ATP mediated cytoprotection is not the main mechanism of protective effect of EPO.
trma ve E itim Hastanesi, Gastroenteroloji Klini i, ANKARA ÖZET Kronik pankreatit tansnda feka... more trma ve E itim Hastanesi, Gastroenteroloji Klini i, ANKARA ÖZET Kronik pankreatit tansnda fekal elastazn klinik önemi Kronik pankreatitte pankreas ekzokrin fonksiyonlarnn de erlendirilmesi hastal n tan ve tedavisinde önemlidir. Günümüzde ara trmaclar kronik pankreatit tans için invaziv olmayan, tansal do rulu u yüksek, rutin çal maya uygun yeni testler ara trmaya yönelmi tir. Fekal pankreatik elastaz-1 (FE-1) pankreatik ekzokrin fonksiyonla-rn de erlendirilmesinde kullanlabilecek noninvaziv bir yöntem olarak orta ve ciddi pankreatik ekzokrin fonksi-yonlarnn tansna imkan vermektedir. Bu çal mada amacmz, gastroenteroloji klini inde ultrasonografi, bilgi-sayarl tomografi, endoskopik retrograd kolonjiyo pankreotografi ile kronik pankreatit tans alm hastalarda non-invaziv pankreas ekzokrin fonksiyonunun göstergesi olarak FE-1 düzeyinin klinik önemini belirlemek, mikro ELISA yöntemi ile belirlenen FE-1 de erleri için en uygun cut-off de erini tespit etmek, yöntemin sensitivite ve spesifitesini belirlemek, tedavi amaçl enzim preperat kullanan kronik pankreatitli hastalarda FE-1 testinin tansal do rulu unu göstermek, kronik pankreatitli hastalarda FE-1 düzeyleri ile serum lipaz düzeyleri arasndaki korelasyonu ara trmaktr. Çal mamz kronik pankreatit tans alan 26 hasta ile 17 sa lkl ki i olu turdu. Kronik pankreatit tans alm hastalarda sa lkl kontrol grubuna göre fekal elastaz-1 düzeyleri dü ük bulundu (p<0,001). FE-1 yöntemi için cut off de eri 240 µg/g olarak bulundu. Yöntemin sensitivite ve spesifitesi sras ile %92,3 ve %70 idi. Tedavi amaçl enzim preparat kullanan kronik pankreatitli hastalarda enzim preparat kullanmayan kronik pankreatitli hastalara göre FE-1 düzeyinde anlaml bir fark bulunamad (p=0,091). Kronik pankreatitli hasta grubunda FE-1 ile lipaz düzeyleri arasnda korelasyon bulunamad (p=0,836). Sonuç olarak Fekal Elastaz-1 testinin, tansal parametre de erlerinin dü ük bulunmasndan dolay kronik pankreatit tansnda destekleyici bir parametre olabilece i, ancak tansal do ruluk için daha çok vakalarla yaplan çal malara ihtiyaç olabilece i ve enzim preparatlarndan etkilenmemesi nedeniyle, bu amaçla kullanlan test parametreleri arasnda bir avantaja sahip oldu u görü üne varld.
Human & Experimental Toxicology, 2011
Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. C... more Accumulation of the widespread environmental toxin cadmium (Cd) in tissues results in toxicity. Cd, which can induce a broad spectrum of biological effects, is a toxic substance and is associated with inflammation and apoptosis. Midkine (MK) has fibrinolytic, antiapoptotic, transforming, angiogenetic and chemotactic activities. After Cd toxicity, we found increased MK expression in liver cells in an in vitro cell culture model. The aim of this study was to determine the possibility of relationship between tissue MK expression levels, tumor necrosis factor α(TNF-α) levels and apoptosis in a chronic Cd toxicity model in rats. Male Wistar rats were exposed to Cd at the dose of 15 parts per million (ppm) for 8 weeks. MK levels were measured in kidney, heart and liver tissue by enzyme-linked-immunosorbent assay (ELISA). MK messenger RNA (mRNA) expression was evaluated by RT-PCR. Tissue apoptosis level was evaluated with tissue caspase-3 activity levels. Accumulation of Cd in liver is higher than the kidney and heart. Cd-treated rats had significantly higher tissue TNF-α and caspase-3 levels when compared with the control rats (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). MK mRNA and protein levels were also significantly upregulated in the Cd-treated group (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, respectively). When compared with apoptosis in tissues, it was more prominent in the liver than kidney and heart. MK level is found increased 3, 1.7 and 1.3× folds in liver, kidney and heart, respectively. Our results showed that chronic Cd administration induces inflammation and apoptosis in rat liver, kidney and heart. MK involved in damage mechanisms of Cd-induced tissues. Further studies will show the underlying mechanism of increased MK expression in Cd toxicity.
Pathophysiology of Haemostasis and Thrombosis, 2011
Cadmium (Cd) is a heavy metal which affects many systems in humans and animals as a consequence o... more Cadmium (Cd) is a heavy metal which affects many systems in humans and animals as a consequence of environmental and industrial pollution. The aim of this study was to investigate the effect of chronic Cd toxicity on blood pressure and plasma viscosity. Experimental group rats were given doses that contained 15 ppm CdCl(2) in drinking water for 8 weeks. The systolic blood pressure and heart rate were measured from rats&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; tails and recorded by plethysmography every two weeks. Blood samples were drawn, Cd levels were determined by atomic absorption spectrophotometer and plasma viscosity values by viscometer. Blood Cd levels were found to be significantly higher in the experimental group compared to the control group (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The whole blood analysis was made by an analyzer. Polymorphonuclear leukocytes and monocytes increased (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and lymphocyte number (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) decreased in the experimental group. Viscosity values were 2.21 ± 0.54 and 1.62 ± 0.31 centipoises in the experimental and control groups, respectively (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In the experimental group, changes in systolic blood pressure between weeks were significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) and were found to be correlated with plasma viscosity (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In the experimental group, changes in heart rate between weeks were significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). According to our findings, Cd toxicity may lead to an increase in blood pressure by increasing plasma viscosity.
Journal of Physiology and Biochemistry, 2004
Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemi... more Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-α level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-α, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 μg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-α levels, and PCs were significantly higher in the I/R group than those in the control group (p<0.05). The administration of leptin decreased these parameters (p<0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p<0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p<0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-α levels and increasing nitrite level. El factor de necrosis tumoral alfa (TNF-α) está implicado en la lesión renal tras isquemia y reperfusión (I/R). Dado que se ha observado que la leptina presenta un efecto citoprotector sobre el tejido renal, se estudia en este trabajo el efecto de la hormona sobre el contenido en el tejido renal de TNF-α, malondialdehido (MDA), niveles de grupos carbonilo protéicos (PC) y de los grupos sulfhidrilo total (SH), y el nivel plasmático de nitrito tras lesión renal por isquemia/reperfusión en rata. Los animales se repartían en tres grupos de 8 ejemplares: control, I/R, e I/R+leptina. Las ratas se sometían a una isquemia renal durante 45 minutos con ulterior reperfusión de una hora. A los del grupo I/R+leptina se les había administrado por vía intraperitoneal leptina (10 μg/kg) 30 minutos antes de la inducción de la isquemia. Los resultados indican que el contenido en MDA, TNF-α y PC está significativamente elevado en el grupo I/R respecto del grupo de control (p<0.05), mientras que el de SH se reduce tras la lesión I/R y el nivel de nitrito en el plasma no varía. El tratamiento con leptina anula los incrementos de los niveles renales de TNF-α, MDA y PC y de la disminución de grupos SH en tejido renal e incrementa el nivel de nitritos plasmáticos por isquemia/reperfusión renal. Estos resultados sugieren que la leptina ejerce un efecto protector sobre la lesión renal inducida por isquemia y reperfusión por la disminución de TNF-α y el aumento plasmático de nitrito.
Journal of Health Science, 2004
Currently, erythropoietin (EPO) treatment in anemic patients is getting more interest, but in lon... more Currently, erythropoietin (EPO) treatment in anemic patients is getting more interest, but in long term, development of hypertension is common problem in EPO treated patients. Since it isn't yet known whether EPO affects directly vascular and/or kidney functions, we aimed to study effects of acute EPO treatment on renal tissue nitrite level, and cardiovascular function and glomerular filtration rate (GFR). Experiments were done under 4 groups. Group I: Sham operated control, group II: 150 IU/kg EPO, group III: 50 mg/kg Nw-nitro-L-arginine methyl ester (L-NAME), group IV: L-NAME+EPO. Femoral artery, vein and bladder were catheterized under anesthesia. After stabilization and first 45 min basal control period, drugs were given i.v. bolus infusion according to the group protocols, then 2 × 45 min clearance periods were followed. EPO infusion increased renal tissue nitrite activity causing GFR increase without any influence on systemic blood pressure. L-NAME alone or together with EPO significantly raised the systemic blood pressure with a partial increase in GFR, but L-NAME treatment significantly reduced tissue nitrite level. The present study for the first time suggests that exogenous EPO treatment increases rat GFR and renal tissue nitrite level without affecting systemic blood pressure.
Journal of Neuro-oncology, 2010
The aim of this work is to investigate whether clomipramine (CIM) and lithium chloride (LiCl) pot... more The aim of this work is to investigate whether clomipramine (CIM) and lithium chloride (LiCl) potentiate the cytotoxicity of vinorelbine (VNR) on SH-SY5Y human neuroblastoma cells in vitro and whether midkine (MK) can be a resistance factor for these treatments. Four groups of experiments were performed for 96 h using both monolayer and spheroid cultures of SH-SY5Y cells: (1) control group, (2) singly applied VNR, CIM, and LiCl, (3) VNR with CIM, and (4) VNR with LiCl. Their effects on monolayer and spheroid cultures were determined by evaluating cell proliferation, bromodeoxyuridine labeling index (BrdU-LI), apoptosis, cyclic adenosine monophosphate (cAMP) and midkine levels, colony-forming efficiency, spheroid size, and ultrastructure. In comparison with the control group, single and combination drug treatments significantly reduced the proliferation index (PI) for 96 h. The most potent reduction of PI was observed with VNR in combination with CIM and LiCl for all time intervals. VNR with CIM and LiCl seemed to be ineffective in reducing BrdU-LI of both monolayer cell and spheroid cultures, spheroid size, and cAMP level. VNR with LiCl increased apoptosis at 24 h, however VNR with CIM increased apoptosis at 96 h. VNR was the most potent drug in inhibiting colony-forming efficiency. The combination of VNR with CIM was the most potent in reducing midkine levels among all groups. Interestingly, the combination of VNR with LiCl led to both nuclear membrane breakdown and disappearance of the cellular membranes inside the spheroids. Both CIM and LiCl seemed to potentiate VNR-induced cytotoxicity, and MK was not a resistance factor for VNR, LiCl, and CIM.
Journal of Physiology and Biochemistry, 2004
Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemi... more Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-α level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-α, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 μg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-α levels, and PCs were significantly higher in the I/R group than those in the control group (p<0.05). The administration of leptin decreased these parameters (p<0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p<0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p<0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-α levels and increasing nitrite level. El factor de necrosis tumoral alfa (TNF-α) está implicado en la lesión renal tras isquemia y reperfusión (I/R). Dado que se ha observado que la leptina presenta un efecto citoprotector sobre el tejido renal, se estudia en este trabajo el efecto de la hormona sobre el contenido en el tejido renal de TNF-α, malondialdehido (MDA), niveles de grupos carbonilo protéicos (PC) y de los grupos sulfhidrilo total (SH), y el nivel plasmático de nitrito tras lesión renal por isquemia/reperfusión en rata. Los animales se repartían en tres grupos de 8 ejemplares: control, I/R, e I/R+leptina. Las ratas se sometían a una isquemia renal durante 45 minutos con ulterior reperfusión de una hora. A los del grupo I/R+leptina se les había administrado por vía intraperitoneal leptina (10 μg/kg) 30 minutos antes de la inducción de la isquemia. Los resultados indican que el contenido en MDA, TNF-α y PC está significativamente elevado en el grupo I/R respecto del grupo de control (p<0.05), mientras que el de SH se reduce tras la lesión I/R y el nivel de nitrito en el plasma no varía. El tratamiento con leptina anula los incrementos de los niveles renales de TNF-α, MDA y PC y de la disminución de grupos SH en tejido renal e incrementa el nivel de nitritos plasmáticos por isquemia/reperfusión renal. Estos resultados sugieren que la leptina ejerce un efecto protector sobre la lesión renal inducida por isquemia y reperfusión por la disminución de TNF-α y el aumento plasmático de nitrito.
Injury-international Journal of The Care of The Injured, 2008
Spinal cord injury (SCI) is a very destructive process for both patients and society. Lipid perox... more Spinal cord injury (SCI) is a very destructive process for both patients and society. Lipid peroxidation is the main cause of the further secondary damage which starts after mechanical destruction of tissues. Recent studies have shown that erythropoietin (EPO) has neuroprotective properties. In this study, we aimed to see the effect of EPO treatment after spinal cord injury on the oxidant and antioxidant enzyme systems and the relationship with the N-methyl-D-Aspartate (NMDA) blockage. Spinal cord injury was produced by epidural compression with a cerebral vascular clip that has a closing force of 40 g for 30 s after a limited multilevel laminectomy (T9-11). Experiment was done in 5 groups: Group1: Sham-operated untraumatised, Group 2: SCI untreated, Group 3: 150 i.u./kg EPO injected i.p. at the end of the first hour following the trauma. Group 4: NMDA receptor antagonist ketamine (100 mg/kg) i.p. Group 5: EPO + ketamine i.p. The experiments were finished after 12 h of the trauma. The spinal cords were excised for biochemical examinations.
Journal of Physiological Sciences, 2006
There is enough evidence that erythropoietin (EPO) may be involved in cardiovascular function. Th... more There is enough evidence that erythropoietin (EPO) may be involved in cardiovascular function. Therefore we have investigated the possible effects of EPO on left ventricular developed pressure, +dP/dt(max), heart rate, tissue cAMP, and nitrite levels. Isolated rat hearts were perfused under constant flow (10 ml/min) conditions with modified Krebs-Henseleit solution and recombinant human erythropoietin at doses of 100, 200, 500, and 1,000 IU/kg was administered as bolus injections. EPO at 100 IU/kg decreased, but higher doses (500 and 1,000 IU/kg) raised the developed pressure and +dP/dt(max). However, it did not affect heart rate or coronary perfusion pressure when all the respective doses were applied. EPO at 100 IU/kg increased nitrite, and at 1,000 IU/kg it raised cAMP. Our results suggest that EPO may produce dose-dependently negative and positive inotropic effects on myocardial contractility in isolated rat hearts. NO and cAMP may be involved in negative and positive inotropic effects of EPO, respectively.
Advances in Therapy, 2008
Introduction Erythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat a... more Introduction Erythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat anaemia in patients on dialysis. In addition, EPO has been shown to have anti-inflammatory properties, which may be important as dialysis patients tend to exist within a chronic, low-grade inflammatory state, and tend to be more susceptible to infections. It has been suggested that EPO has direct immunomodulatory potency on monocytes/macrophages. Methods In this study, we aimed to clarify the effects of EPO during the inflammatory processes in human mononuclear phagocytic cells by monitoring the secretion of the following cytokines; midkine, tumour necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). For this purpose, U937 human histiocytic lymphoma cell lines were used. Time-dependent effects of varying doses of EPO (0.1 to 50 IU/ml) treatment during lipopolysaccharide (LPS)-mediated cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide test. LPS-stimulated midkine secretion was measured immunohistochemically and quantification of TNF-α, IL-6 and midkine secretion was achieved by ELISA. Results EPO treatment prevented the direct toxic effects of LPS on the U937 cells. TNF-α, IL-6 and midkine secretions were found to increase in the U937 cells in response to LPS treatment. Interleukin-6 response was varied in a doseand time-dependent manner. Conclusion Treatment with EPO significantly inhibits the LPS-induced secretion of midkine and TNF-α regardless of the dosage. The data presented here provide the first evidence to indicate that EPO treatment directly reverses some of the cytotoxic and secretory effects of LPS in mononuclear cells. Inhibition of midkine secretion might be responsible for the anti-inflammatory role of EPO.