Fenofibrate Treatment Enhances Antioxidant Status and Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Rats

Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-α activator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg−1 day−1) for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-α level in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

<p>Abstract</p> <p>Background</p> <p>Obesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.</p> <p>In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.</p> <p>Results</p> <p>In PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p> <p>Conclusions</p> <p>We found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.</p

Streptozosin ile oluşturulmuş sıçan diyabet modelinde fenofibratin endotel disfonksiyonuna etkisi

Bu tezin, veri tabanı üzerinden yayınlanma izni bulunmamaktadır. Yayınlanma izni olmayan tezlerin basılı kopyalarına Üniversite kütüphaneniz aracılığıyla (TÜBESS üzerinden) erişebilirsiniz.ÖZET Deneysel diyabet gelişiminde ve bina bağlı damar yanıtlarındaki bozulmadan sorumlu olan faktörlerden birisi serbest oksijen radikalleridir. Çalışma deneysel diyabet modelinde antioksidan etkinliği olduğu öne sürülen fenofibratın damar yanıtlarına etkisini araştırmıştır. Sıçanlarda diyabet oluşturmak için 55 mg/kg streptozosin intraperitoneal yolla verildi. Diyabetik sıçanlara Fenofibrat (150 mg/kg) bir grupta diyabet oluştuktan 6 hafta sonra ; diğer grupta diyabetin hemen başlangıcında verildi. Tüm gruplarda deney protokolü diyabet oluşturuşlduktan 10 hafta sonra tamamlandı. Diyabetik sıçan grubunda kontrole göre azalmış bulunan asetilkolin gevşeme yanıtı fenofibrat tedavisi ile düzeldi. Reseptör aracısız A23 187, NO prekürsörü L- Arginin ve direkt düz kas gevşetici ajan olan SNP yanıtlarında ise gruplar arasında anlamlı bir fark saptanmadı. Diyabetik sıçan grubunda fenilefrinle olan kasılma yanıtları kontrol grubuna göre arttı. Fenofibrat tedavisi artmış olan kasılma ynıtlarını belirgin olarak düzeltti. Diyabetik grubun endotelsiz aort preparatlarında fenilefrinle olan kasılma yanıtları endotelli preparatlarda farklı bulunmadı. Kontrol grubunun endotelsiz aort preparatlarında ise fenilefrin kasılma yanıtları endotelli preparatlara göre artış gösterdi. Potasyum klorür depolarizasyonu ile elde edilen kasılma yanıtları gruplar arasında istatistiksel olarak anlamlı bir fark oluşturmadı. Fenofibrat tedavisi diyabetik gruptaki kilo kaybına ve kan şekeri düzeylerine etki göstermedi. Diyabetik grupta artmış olan kolesterol ve trigilserit düzeyleri tedavi gruplarında düşse de istatistiksel olarak anlamlı bulunmadı. Bulgularımız diyabette damar yanıtlarının bozulduğunu ve bu bozulmada endotel hasarının rolü olduğunu düşündürmektedir. 77Çalışmamız, diyabetteki endotel disfonksiyonunun düzeltilmesi ve diyabetik hastalardaki mikro ve makrovasküler hastalıkların riskini azaltmada fenofibratın hipolipidemik etkisinden bağımsız olarak etkili olabileceğini düşündüren deneysel bir göstergedir. 7

Gebelerde ilaç kullanımı: Son bir yıllık deneyim

AIM: The aim of this study was to provide retrospective information about the prescribed drugs among pregnant woman who referred to Ege University Department of Pharmacology and Clinical Pharmacology. MATERIAL-METHOD: A retrospective study was conducted among pregnant woman who referred to our department between January 1, 2005 and December 31, 2005. Initially, all women were evaluated by an obstetrician and and the effects of the drugs during pregnancy was determined according to the United States Food and Drug Administration (FDA) risk classification system database RESULTS: 345 pregnant women were evaluated during the study. 43 % of the women were referred from Ege University Medical Faculty Department of Obstetrics and Gynaecology and 24 % from public hospitals, whereas 33% were consigned from doctor offices. 30% of the women were between 25-29 years of age. The most commonly prescribed drugs were anti-infectives (26.6 %), opioid and non-opioid analgesics (18.3%), antidepressants (8.4%) and flu medications (8.2 %). According to the FDA classification 1.4% of the prescribed drugs were in category A, 42.9% were in category B, 42.4% were in category C, 6.7% were in category D and 3.1% were in category X. 83.6% of the pregnant women had medications during first trimester of their pregnancies. Only 10% of the women received a single drug. CONCLUSIONS: Our study reveals that during their pregnancies an important proportion of women encounter drugs which might have a teratogenic potential. This proportion. can be reduced by interrogation of the patient about pregnancy before prescribing drugs.AMAÇ: Bu çalışma Ege Üniversitesi Tıp Fakültesi Farmakoloji ve Klinik Farmakoloji Anabilim Dalı’na gebeliği sırasında ilaç kullanılması nedeniyle sevk edilen hastaların geriye dönük olarak değerlendirilmesini amaçlamıştır. GEREÇ-YÖNTEM: Bu çalışmada 1 Ocak 2005- 31 Aralık 2005 tarihleri arasında kliniğimize başvuran hastalar retrospektif olarak değerlendirilmiştir. Tüm hastalar öncelikle bir kadın hastalıkları ve doğum uzmanı tarafından görülmüş olup ilaçların gebeliğe etkileri için temel olarak Amerika Birleşik Devletleri’nin Gıda ve İlaç Dairesi ( FDA ) veritabanı kullanılmıştır. BULGULAR: Çalışmamızda 345 gebe değerlendirilmiştir. Olguların % 43’ü Ege Üniversitesi Tıp Fakültesi Hastanesi’nin, % 24’ü diğer kamu hastanelerinin kadın hastalıkları ve doğum kliniklerinden, % 33’ü ise özel muayenehanelerden sevk edilmişti. Gebelerin % 30’u 25-29 yaş grubu içerisindeydi. Gebelik sırasında en sık kullanılan ilaçlar % 26.6 antiinfektifler, % 18.3 opioid ve opioid olmayan analjezikler, % 8.4 antidepresanlar, % 8.2 antigribal ilaçlardı. FDA sınıflamasına göre A kategoride yer alan ilaçlar % 1.4, B kategoride yer alan ilaçlar % 42.9, C kategoride yer alan ilaçlar % 42.4, D kategoride yer alan ilaçlar % 6.7 ve X kategoride yer alan ilaçlar % 3.1 idi. Gebelerin % 83.6 sı bu ilaçları ilk trimestirda kullanmıştı. Gebelerin sadece % 10’u tek bir etken maddeye maruz kalmıştı. SONUÇ: Kadınlar gebelikleri sırasında FDA sınıflamasına göre teratojenite potansiyeli olan ilaçlara önemli oranda maruz kalabilirler. İlaç reçetelendirilmesi sırasında gebeliğin sorgulanması bu oranı azaltabilir

Esophageal Epithelial Resistance and Lower Esophageal Sphincter Muscle Contraction Increase in a Chronic Diabetic Rabbit Model

WOS: 000379013300017PubMed ID: 26972084Esophageal motility disorders and possibly gastroesophageal reflux disease are common in patients with diabetes mellitus. We aimed to investigate both the electrophysiological characteristics of the esophageal epithelium and the contractility of the lower esophageal sphincter (LES) muscle in alloxane-induced diabetic rabbits. Electrophysiological properties were measured using an Ussing chamber method. An acid-pepsin model was employed with pH 1.7 or weakly acidic (pH 4) Ringer and/or pepsin. Smooth muscle strips of the LES were mounted in an isolated organ bath. Contractile responses to an electrical field stimulation and cumulative concentrations of acetylcholine were recorded. Contractility of the muscle strips were tested in the presence of Rho-kinase inhibitor (Y-27632) and nonspecific nitric oxide inhibitor (L-NAME). The resistance of diabetic tissue perfused in the pH 1.7 Ringer decreased 17 %; pepsin addition decreased it by 49 %. The same concentrations caused a more distinct loss of resistance in the control tissues (22 and 76 %, p < 0.05). The perfusion of tissues in increased concentrations of luminal and serosal glucose did not change the tissue resistance and voltage. Diabetes significantly increased both the electrical field stimulation and acetylcholine-induced contractions in the LES muscle strips (p < 0.01). Incubation with Y-27632 significantly decreased the acetylcholine-induced contractions in a concentration-dependent manner (p < 0.01). The acid-pepsin model in the diabetic rabbit esophageal tissue had less injury compared with the control. The diabetic rabbit LES muscle had higher contractility, possibly because of the activation of the Rho-Rhokinase pathway. Our results show that in a chronic diabetic rabbit model the esophagus resists reflux by activating mechanisms of mucosal defense and increasing the contractility of the LES.Ege University Scientific Research CouncilEge University [2011-TIP-025]This study has been supported by Ege University Scientific Research Council (project no. 2011-TIP-025)

Therapeutic concentrations of tacrolimus do not interfere with endothelial nitric oxide synthesis in rat thoracic aortas and coronary arteries

WOS: 000250415100008PubMed ID: 18049307This study aimed to investigate the potential effect of in vivo administration of immunosuppressive agent FK-506 (tacrolimus) on the endothelial function of rat thoracic aortas with respect to nitric oxide (NO) synthesis. In vitro effect of the drug on NO synthesis in cultured rat coronary microvascular endothelial cells (CMEC) was also studied. In vivo administration of tacrolimus (1 mg/kg/d, intramuscular) to rats for 14 days resulted in decreased relaxant responses to the higher concentrations (1 to 30 mu M) of acetylcholine in the aortas; however, responses to calcium ionophore A23187, sodium nitroprusside, L-arginine, and L-NAME did not change significantly. No changes were observed in phenylephrine-induced contractions in endothelium-denuded or -intact preparations. Administration of the vehicle for 14 days did not affect these parameters. In order to evaluate the in vitro effect of tacrolimus on NO release, CMEC isolated from rat hearts were incubated with either tacrolimus (0.01, 0.1 mu M) or the vehicle. Basal, calcium ionophore-stimulated, or interleukin-IP-induced NO synthesis was determined by measuring total nitrite in the media. Neither tacrolimus nor the vehicle changed nitrite accumulation. It has been concluded that therapeutic concentrations of tacrolimus do not alter NO production in rat thoracic aorta or cultured CMEC however, it impairs relaxant responses of rat aorta induced by higher concentrations of acetylcholine, possibly through changes in the downstream of receptor activation or through an imbalance between endothelium-dependent relaxant and contracting factors within the endothelium in favor of the contracting factor(s)