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Beneficial effects of melatonin on serum nitric oxide, homocysteine, and ADMA levels in fructose-fed rats.

Abstract Context: Melatonin, a pineal hormone and a potent antioxidant, has important roles in metabolic regulation. Objective: This study investigated serum asymmetric dimethylarginine (ADMA), homocysteine (Hcy), nitric oxide (NO) levels, known to be reliable markers of cardiovascular diseases, and determined possible protective effects of melatonin in fructose-fed rats. Materials and methods: Sprague–Dawley rats were divided into four groups: control, fructose, melatonin, and fructose plus melatonin. Metabolic syndrome was induced in rats by 20% (w/v) fructose solution in tap water, and melatonin was administered at the dose of 20 mg/kg bw per day by oral gavage. After 8 weeks, serum lipids, glucose, insulin, ADMA, Hcy, and NOx (the stable end products of NO) levels were quantified. Results: Fructose administration caused a statistically significant increase in systolic blood pressure (SBP), serum insulin, triglycerides, and very low-density lipoprotein (VLDL)–cholesterol levels compared with the control group and the metabolic syndrome model was successfully demonstrated. In comparison with the control group, fructose caused a significant increase in serum ADMA, Hcy, and NOx levels. Melatonin counteracted the changes in SBP, serum ADMA, and Hcy levels found in rats both alone and administered with fructose. Discussion and conclusion: These results show that high fructose consumption leads to elevated SBP, atherogenic lipid profile, increased serum ADMA, and Hcy levels and melatonin treatment has beneficial effects on these biochemical parameters in rats. Melatonin might be beneficial for the prevention and/or treatment of the cardiovascular complications of metabolic syndrome not only by reducing the well-known risk factors of the disease but also by diminishing blood ADMA and Hcy levels.

The Relationship Between Taurine and 3-Nitrotyrosine Level of Hepatocytes in Experimental Endotoxemia

It has been proposed that taurine may function as an oxidant in a dose-dependent manner in vivo and in vitro. The present study was carried out to investigate the relationship between taurine concentration and 3-nitrotyrosine level, a stable marker of peroxynitrite action, in hepatocytes of guinea pig in endotoxemia before and after taurine administration. The levels of taurine and 3-nitrotyrosine were measured by HPLC method. In the present study, taurine was low concentration in hepatocytes exposed to endotoxemia. In taurine plus endotoxin treated animals, HPLC analysis showed higher taurine level compared with animals only supplemented with taurine. But 3-nitrotyrosine levels were same in both taurine alone and taurine plus endotoxin groups. In conclusion, taurine is able to prevent the damaging effect of peroxynitrite, at concentration measured in hepatocytes, in our experimental conditions.

Investigation of the effect of intracolonic melatonin gel formulation on acetic acid-induced colitis

Abstract The aims of the present study were to develop a colon-specific gel formulation of melatonin with sodium alginate and to evaluate its in vitro characteristics and intracolonic performance on oxidative stress parameters, such as nitric oxide (NOx), malondialdehyde (MDA) and glutathione (GSH) levels in rats with acetic acid-induced colitis. The melatonin-alginate gel formulations were prepared and their physico-pharmaceutical properties were determined. Formulation M5, which contained 3% of sodium alginate and 20% polyethylene glycol, was used for in vivo studies. The in vivo studies were conducted in rats with acetic acid-induced colitis. NOx, MDA and GSH levels were determined and histological investigations were performed. It was found that formulation M5 was the most suitable formulation for the colon-specific melatonin gel, in terms of pH, viscosity, drug release and mucoadhesion properties. The MDA levels in the tissues of Group 2 (treated with an intracolonic gel formulation without melatonin) were found to be significantly higher than in Group 1 (the untreated group). NOx levels decreased with the intracolonic and systemic melatonin treatment in the colitis-induced rats. Neither intracolonic nor intra-peritoneal (IP) melatonin treatment affected GSH levels. The epitelization of the colon tissues in groups administered with intracolonic melatonin, IP melatonin, and the intracolonic gel formulation without melatonin was much better than that found in the untreated group. It was concluded that melatonin participated in various defense mechanisms against the colonic inflammatory process, and that the dose, route and formulation type were the most important parameters in the effectiveness of melatonin.

The effects of melatonin on brain nitrosative stress and energy balance in fructose-mediated metabolic syndrome model / Fruktoz-aracılı metabolik sendrom modelinde melatoninin beyinde nitrozatif stres ve enerji dengesi üzerine etkisi

Abstract Objective: Metabolic syndrome (MetS), one of the common health problems seen with increasing frequency in today’s modern societies, is also a important risk factor for neurological disorders such as stroke, depression, Alzheimer’s disease. On the other hand, melatonin is a neurohormone, has potent antioxidant and neuroprotective activities. In the present study, we aimed to investigate the possible protective effects of melatonin administration on brain tissue in fructose-mediated MetS model. Methods: Male adult Sprague-Dawley rats were randomly divided into four groups (n=8); control, fructose, melatonin and fructose plus melatonin. MetS was induced by fructose solution 20% in tap water, and melatonin was administered at the dose of 20 mg/kg bw/day by oral gavage. Systolic blood pressures (SBP) were measured by tail-cuff method. After the experimental period of 8 weeks, serum triglyceride, glucose, insulin, and tissue ATP/ADP ratio, nitric oxide (NOx) and 3-nitrotyrosine (3-NT) levels were measured. Also tissue endothelial and inducible nitric oxide synthase (eNOS and iNOS) protein levels were determined. Results: Fructose consumption increased SBP, serum triglyceride, insulin levels and induced insulin resistance significantly compared to control group and MetS model was successfully demonstrated. In comparison with control group, fructose administration did not cause significant changes in tissue ATP/ADP ratio and 3-NT levels. NOx levels did not change significantly among groups, and iNOS-eNOS proteins were not detected in any groups. Interestingly, tissue 3-NT levels were elevated significantly while ATP/ADP ratio was diminished in fructose plus melatonin group compare with both control and fructose groups. Conclusion: These results indicate that high fructose diet for 8 weeks does not influence nitric oxide production, energy metabolism and protein nitration in brain. Nevertheless melatonin acted as a pro-oxidant at that dose when administered with fructose. Özet Amac: Metabolik Sendrom (MetS), bugunun modern toplumlarında yuksek gorulme sıklığına sahip, yaygın sağlık problemlerinden biri olup; felc, depresyon ve Alzheimer hastalığı gibi norolojik bozukluklar icin de onemli bir risk faktoru oluşturmaktadır. Diğer taraftan, melatoninin guclu antioksidan ve noron koruyucu ozelliklere sahip bir norohormon olduğu bilinmektedir. Bu calışmada, fruktoz-aracılığıyla MetS oluşturulan sıcanlarda, melatonin uygulanmasının beyin dokusunda olası koruyucu etkilerinin araştırılması amaclanmıştır. Metod: Yetişkin erkek Sprague-Dawley sıcanlar kontrol, fruktoz, melatonin ve fruktoz+melatonin olmak uzere rastgele 4 gruba ayrıldı (n=8). MetS, icme suyu icerisinde %20 oranında fruktoz verilerek oluşturuldu ve melatonin 20 mg/kg/gun dozunda oral gavaj yoluyla uygulandı. Sistolik kan basıncı (SKB) kuyruktan kan basıncı olcum yontemi ile belirlendi. Sekiz haftalık deney periyodu sonunda, serum trigliserit, glukoz ve insulin seviyeleri ile doku ATP/ADP oranı, nitrik oksit (NOx), 3-nitrotirozin (3-NT) seviyeleri olculdu. Ayrıca, dokulardaki endotelyal ve induklenebilir nitrik oksit sentaz (eNOS ve iNOS) protein duzeyleri belirlendi. Bulgular: Kontrol grubuyla karşılaştırıldığında, fruktoz grubunda SKB, serum trigliserit, insulin duzeylerinin ve insulin direncinin belirgin şekilde arttığı belirlenerek, MetS modelinin başarıyla oluştuğu gozlenmiştir. Fruktoz uygulanan grupta, doku ATP/ADP oranı ve 3-NT duzeylerinde kontrol grubuna gore anlamlı bir farklılık bulunamamıştır. Doku NOx seviyeleri tum gruplar arasında belirgin bir farklılık gostermezken; dokularda iNOS ve eNOS proteinleri saptanamamıştır. Fruktoz+melatonin grubunda ise kontrol ve fruktoz gruplarıyla karşılaştırıldığında, ilginc bir şekilde 3-NT duzeyleri artarken, ATP/ADP oranı belirgin şekilde azalmıştır. Sonuc: Bu sonuclar, 8 haftalık yuksek fruktoz diyetinin beyin dokusunda nitrik oksit uretimi, enerji metabolizması ve protein nitrasyonu uzerinde herhangi bir etkisinin olmadığını gostermiştir. Melatoninin ise, beklenenin aksine, bu dozda ve fruktozla birlikte uygulandığında pro-oksidan etki gosterdiği bulunmuştur.