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Dilek Yavuz,
Halil Tuğtepe,
Şule Çetinel,
Suheyla Uyar,
Handan Kaya,
Goncagül Haklar,
Sabahat Civelek,
Oğuzhan Deyneli,
Tangül Şan, Gülden Burçak,
Sema Akalin
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ABSTRACT: Advanced glycoxidation end products have been implicated in delayed diabetic wound healing. In this study, we evaluated the effects of aminoguanidine, which is an advanced glycation and nitric oxide (NO) synthase inhibitor, on extracellular matrix protein expression, collagen configuration, and nitrite/nitrate levels in wounds of diabetic rats. Sixteen Wistar male rats were made diabetic by streptozotocin. Of these, eight rats were given AG (aminoguanidine bicarbonate (AG) (group DAG) in their drinking water, and eight rats were followed as diabetic paired controls (group D). Eight healthy rats were followed as the healthy control group (group H). At the eighth week, a 2 × 2 cm area full-thickness skin defect was created. The degree of contraction of the open wounds was evaluated for 2 weeks duration. On the 15th postoperative day, wound surface areas were measured, and wound specimens and blood samples were collected. The shrinking percentage of the wounds was small in both groups H and DAG compared with group D (p < 0.05). Similar to healthy rats, the aminoguanidine-treated diabetic rats had very strong transforming growth factor (TGF)-β1 expression in granulation tissue and intact skin in comparison with diabetic controls. In the diabetic group, the intact skin demonstrated sparsely distributed regular collagen fibers in the granulation zone, and the regular pattern of collagen fibers was lost. In conclusion, aminoguanidine improves wound healing, restores growth factor TGF-β1 expression, and preserves collagen ultra structure, whereas it has no prominent effect on NO levels within wound tissue in diabetic rats.
07/2009; 31(3):229-243.
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ABSTRACT: We evaluated the plasma homocysteine (tHcy) and nitric oxide metabolites (nitrite plus nitrate; NOx) data of consecutive patients undergoing diagnostic coronary angiography (n=79) with respect to the presence and severity of coronary artery disease (CAD), the presence of acute coronary syndromes (ACS), and the risk status of patients. Hyperhomocysteinemia (>15 micromol/L) was detected in 11% of the controls (n=19) and 37% of CAD patients (n=60) (p=0.03). Plasma tHcy in CAD patients was not significantly different from controls, but those with 3-vessel disease had a significantly higher tHcy concentrations than did controls (p=0.049). The patients with 3-vessel disease and ACS had the highest concentrations of tHcy (16.9 +- 4.4 micromol/L), and the difference from the ACS patients with 1- and 2-vessel involvement was significant (p=0.03). In patients with 1-vessel involvement, tHcy was correlated with NOx (r=0.62, p=0.005); in patients with 2- and 3-vessel disease this correlation could not be observed. The high-risk patients (n=51) had a higher mean number of vessel involvement and tHcy (p<0.001, p<0.05, respectively) but lower NOx (p<0.05) when compared to the low-risk patients (n=28). It appears that in the early stages of atherosclerosis hyperhomocysteinemia causes an increase in NOx production, but with progression of the disease this compensatory increase disappears.
Acta medica Okayama 03/2006; 60(1):35-41. · 0.84 Impact Factor
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ABSTRACT: 1. Accumulating evidence suggests that oxidative and glycative stress is enhanced in diabetes. Oxidative stress induces DNA damage. In the present study, we assessed the 8-oxo-2'-deoxyguanosine (8-oxodG) content of DNA, an indicator of oxidative DNA damage, in streptozotocin (STZ)-induced diabetic (n = 21) and control rats (n = 18). 2. Rats were rendered diabetic by intraperitoneal administration of STZ at a dose of 65 mg/kg. Glucose was determined by glucose oxidase and glycated haemoglobin (GHb), an indicator of glycative stress, was determined by agarose-boronate affinity chromatography. 8-Oxo-2'-deoxyguanosine within the DNA (ratio of 8-oxodG to deoxyguanosine (dG)) was assessed by HPLC in conjunction with both electrochemical (8-oxodG) and diode array (dG) detection. 3. Glucose, GHb and the extent of oxidative DNA damage in the liver of STZ-diabetic rats were much higher compared with control rats. There was a correlation between GHb and 8-oxodG/10(5) dG levels in control (r = 0.756, P < 0.001) and diabetic groups (r = 0.468, 0.02 < P < 0.05). 4. These results clearly show that oxidative damage to hepatic nuclear DNA increases in the diabetic state and that this increase is correlated with glycative stress.
Clinical and Experimental Pharmacology and Physiology 09/2005; 32(8):663-6. · 1.85 Impact Factor
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ABSTRACT: Oxygen free radical mediated tissue damage is well established in pathogenesis of acute pancreatitis (AP). Whether nitric oxide (NO) plays a deleterious or a protective role is unknown. In alcohol-induced AP, we studied NO, lipooxidative damage and glutathione in pancreas, lung and circulation.
AP was induced in rats (n = 25) by injection of ethyl alcohol into the common biliary duct. A sham laparatomy was performed in controls (n = 15). After 24 h the animals were killed, blood and tissue sampling were done.
Histopathologic evidence confirmed the development of AP. Marked changes were observed in the pulmonary tissue. Compared with controls, the AP group displayed higher values for NO metabolites in pancreas and lungs, and thiobarbituric acid reactive substances in circulation. Glutathione was lower in pancreas and in circulation. Glutathione and NO were positively correlated in pancreas and lungs of controls but negatively correlated in circulation of experimental group. In the experimental group, plasma thiobarbituric acid reactive substances were negatively correlated with pancreas thiobarbituric acid reactive substances but positively correlated with pancreas NO.
NO increases in both pancreas and lungs in AP and NO contributes to the pathogenesis of AP under oxidative stress.
World Journal of Gastroenterology 05/2005; 11(15):2340-5. · 2.47 Impact Factor
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Dilek Yavuz,
Halil Tuğtepe,
Sule Cetinel,
Suheyla Uyar,
Handan Kaya,
Goncagül Haklar,
Sabahat Civelek,
Oguzhan Deyneli,
Tangül San, Gülden Burçak,
Sema Akalin
[show abstract]
[hide abstract]
ABSTRACT: Advanced glycoxidation end products have been implicated in delayed diabetic wound healing. In this study, we evaluated the effects of aminoguanidine, which is an advanced glycation and nitric oxide (NO) synthase inhibitor, on extracellular matrix protein expression, collagen configuration, and nitrite/nitrate levels in wounds of diabetic rats. Sixteen Wistar male rats were made diabetic by streptozotocin. Of these, eight rats were given AG (aminoguanidine bicarbonate (AG) (group DAG) in their drinking water, and eight rats were followed as diabetic paired controls (group D). Eight healthy rats were followed as the healthy control group (group H). At the eighth week, a 2 x 2 cm area full-thickness skin defect was created. The degree of contraction of the open wounds was evaluated for 2 weeks duration. On the 15th postoperative day, wound surface areas were measured, and wound specimens and blood samples were collected. The shrinking percentage of the wounds was small in both groups H and DAG compared with group D (p < 0.05). Similar to healthy rats, the aminoguanidine-treated diabetic rats had very strong transforming growth factor (TGF)-beta1 expression in granulation tissue and intact skin in comparison with diabetic controls. In the diabetic group, the intact skin demonstrated sparsely distributed regular collagen fibers in the granulation zone, and the regular pattern of collagen fibers was lost. In conclusion, aminoguanidine improves wound healing, restores growth factor TGF-beta1 expression, and preserves collagen ultra structure, whereas it has no prominent effect on NO levels within wound tissue in diabetic rats.
Endocrine Research 01/2005; 31(3):229-43. · 0.97 Impact Factor
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Dilek Yavuz,
Halil Tuğtepe,
Sule Cetinel,
Suheyla Uyar,
Handan Kaya,
Goncagül Haklar,
Sabahat Civelek,
Oguzhan Deyneli,
Tangül San, Gülden Burçak,
sema akalin
Endocrine Research 01/2005; 31(3-01):229-43. · 0.97 Impact Factor
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ABSTRACT: The effects of hyperthyroidism on oxidative DNA damage in liver tissue and modification by vitamin C supplementation were investigated in rats. Animals were rendered hyperthyroid by administration of L-thyroxine (0.4 mg/100 g food) for 25 d. In the plasma samples, T(3), T(4), and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay and ascorbate spectrophotometrically. Oxidative damage to hepatic nuclear DNA was determined by measuring deoxy-guanosine (dG) and 8-oxodG by high-performance liquid chromatography with diode array detector electrochemical detection (HPLC-DAD-ECD). In hyperthyroidism, 8-oxodG/(10(5) dG) levels were significantly higher and plasma vitamin C levels lower than in control rats. The results of this experimental study show that oxidative damage to hepatic nuclear DNA increases in the hyperthyroid state and that vitamin C was not effective in preventing this damage.
Journal of Toxicology and Environmental Health Part A 04/2004; 67(5):413-20. · 1.83 Impact Factor
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ABSTRACT: The effects of nitric oxide synthase (NOS) inhibition by Nw-nitro-L-arginine methyl ester (L-NAME) administration on oxidative stress parameters were investigated in streptozotocin (STZ) induced diabetic rats. Lipid peroxidation as reflected by thiobarbituric acid reactive substances (TBARS) was insignificantly higher in diabetic rats. Plasma NO2+NO3 values (p < 0.05) and erythrocyte CuZn superoxide dismutase (CuZn SOD) and glutathione peroxidase (GSH Px) activities were significantly higher (p < 0.01, p < 0.001, respectively) in diabetic rats. L-NAME administration to diabetic rats caused significantly lower CuZn SOD and GSH Px activities (p < 0.01) and NO2+NO3 values (p < 0.001), whereas a significantly higher GSH level (p < 0.01). TBARS/GSH ratio was significantly higher in diabetic rats than controls (p < 0.05) and significantly lower in L-NAME administered diabetic rats than diabetic rats (p < 0.05). This experimental study highlightens the importance of NOS inhibition by L-NAME in the attenuation of oxidative stress in STZ diabetic rats.
The Tohoku Journal of Experimental Medicine 04/2003; 199(4):205-10. · 1.24 Impact Factor
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ABSTRACT: This experimental study was designed to examine whether hyperuricemia in hypothyroidism is associated with insulin resistance. For induction of hypothyroidism, rabbits (n = 12) were administered methimazole orally (75 mg/100 g food) for 30 days. T3, T4 and TSH values measured in plasma prior to and at the end of the experimentation period revealed the establishment of hypothyroidism. In the euthyroid and hypothyroid states of rabbits, crystalline porcine insulin was administered (0.1 unit/kg body weight) intraperitoneally and plasma glucose was measured at 0, 15, 30, 45 and 60 minutes. Sum of post insulin infusion glucose values was considered to reflect insulin resistance. Creatinine clearance (GFR) and uric acid clearance (CuA) were determined. Additionally, triglycerides were measured in plasma and Mg2+ both in erythrocytes and in plasma. Due to hypothyroidism: i) The glycemic response to insulin was not altered. ii) GFR and CuA were both decreased but CuA/GFR unchanged. iii) Triglycerides in plasma decreased. iv) Mg2+ concentration increased in plasma whereas decreased in erythrocytes. Several associations were observed between the variables on correlation analysis. On the basis of our data, it could be suggested that insulin resistance does not exist in hypothyroidism. Hyperuricemia observed in hypothyroidism should be considered to be secondary to decreased renal excretion but not as an indicator of insulin resistance.
The Tohoku Journal of Experimental Medicine 03/2003; 199(2):59-68. · 1.24 Impact Factor
