PubMed İndeksli Yayınlar
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Browsing PubMed İndeksli Yayınlar by Subject "Aging"
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Item A pyridoindole antioxidant SMe1EC2 regulates contractility, relaxation ability, cation channel activity, and protein-carbonyl modifications in the aorta of young and old rats with or without diabetes mellitus(2018) Arı, Nuray; Eczacılık FakültesiWe studied the effects of treatment with SMe1EC, a hexahydropyridoindole antioxidant, on vascular reactivity, endothelial function, and oxidonitrosative stress level of thoracic aorta in young and old rats with or without diabetes mellitus. The rats were grouped as young control (YC 3 months old), old control (OC 15 months old), young diabetic (YD), old diabetic (OD), young control treated (YCT), old control treated (OCT), young diabetic treated (YDT), and old diabetic treated (ODT). Diabetes was induced by streptozotocin injection and subsequently SMe1EC2 (10 mg/kg/day, p.o.) was administered to YCT, OCT, YDT, and ODT rats for 5 months. In young and old rats, diabetes resulted in hypertension, weight loss, hyperglycemia, and hypertriglyceridemia, which were partially prevented by SMe1EC2. SMe1EC2 also inhibited the diabetes-induced increase in aorta levels of AGEs (advanced glycosylation end-protein adducts), 4-HNE (4-hydroxy-nonenal-histidine), 3-NT (3-nitrotyrosine), and RAGEs (receptors for AGEs). The contractions of the aorta rings to phenylephrine (Phe) and KCL did not significantly change, but acetylcholine (ACh) and salbutamol relaxations were reduced in OC compared to YC rats. Diabetes induction increased Phe contractions in YC and OC rats, KCL contractions in YC rats, and did not cause further inhibition in already inhibited ACh and salbutamol relaxations in OC rats. We have achieved the lowest levels of ACh relaxation in YD rats compared to other groups. SMe1EC2 did not change the response of aorta to ACh, salbutamol and Phe in YC rats, and ameliorated ACh relaxations in OC and YD but not in OD rats. In YDT and ODT rats, increased Phe and KCL contractions, high blood pressure, and impaired salbutamol relaxations were amended by SMe1EC2. Phe contractions observed in YD and OD rats as well as KCl contractions observed in OC rats were the lowest levels when the rats were treated with SMe1EC2. When the bath solution was shifted to cyclopiazonic acid (CYP) or CYP plus Ca2+-free medium, the contraction induced by a single dose of Phe (3 × 10-6 M) was more inhibited in YD and OD than in YC but not in OC rats. In SMe1EC2-treated rats, neither the presence of CFM nor CFM plus CYP exhibited a significant change in response of aorta to a single dose of Phe. These findings suggest that α1-adrenergic receptor signaling is activated in both age groups of diabetic rats, diabetes activates K+-depolarization and calcium mobilization via CaV especially in the aorta of young rats, and sensitizes the aorta of old rats to the regulating effect of SMe1EC2. ACh relaxations were inhibited in YC rats, increased in OC rats and unchanged in YD and OD rats when aortic rings pretreated with TEA, an inhibitor of calcium-activated K+ channels (KCa), or 4-aminopyridine (4-AP), an inhibitor of voltage-sensitive K+ channels (KV). ACh relaxations were inhibited in YCT, OCT, and YDT rats in the presence of 4-AP or TEA. In ODT rats, 4-AP did not change ACh relaxation but TEA inhibited. These findings suggest that the contribution of Kv and KCa to ACh relaxation is likely upregulated by SMe1EC2 when the relaxations were inhibited by aging or diabetes. We conclude that SMe1EC2 might be a promising agent for aging and diabetes related vascular disorders.Item Age- and sex-dependent alteration of functions and epigenetic modifications of vessel and endothelium related biomarkers(2018) Akçali, Can; Tıp FakültesiAging is a main risk factor for development of cardiovascular diseases associated with the impairment of endothelial function in both sexes. In the present study, age-related changes in vascular responsiveness, epigenetic modifications of vessel wall, and blood biomarkers related to endothelial functions were examined in an age- and sex-dependent manner. Acetylcholine (ACh)-induced relaxations of the aorta were decreased in 3-, 6-, and 12-month-old rats compared to those in 1-month-old female rats. In males, maximum relaxations related to ACh were higher in 1- and 6-month-old rats than in 3- and 12-month-old rats. Plasma levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA) decreased with age in female rats, and total antioxidant capacity (TAC) and hydrogen sulfide (H 2S) levels displayed biphasic alterations. In male rats, plasma levels of NO, TAC, and ADMA decreased with age, and H2S levels increased. Aging also caused a sex-dependent alteration in epigenetic modification of vessels. Expressions of H3K27me2, H3K27me3, H3K36me2, and H3K36me3 were much higher in vessels of 12-month-old female rats compared to those in younger age groups. These results indicate that vascular functions, epigenetic modifications of vessels, and plasma levels of endothelium-related biomarkers are affected by age and sex. These findings could be important for the assessment of vascular status over the course of the life span.Item Evaluation of the lifespan extension effects of several Turkish medicinal plants in Caenorhabditis elegans(2018) Ergen, Nuri; Biyoteknoloji EnstitüsüResearch on longevity is important to both prolong lifespan and support healthy aging. Natural products are widely being utilized and used as new resources for drug molecules. Caenorhabditis elegans is an advantageous organism for longevity research and age-related diseases. In this study, we tested a number of plant extracts for their effects on C. elegans longevity. In lifespan assays, agesynchronized wild-type C. elegans specimens were treated with different concentrations of plant extracts. Plant extracts were prepared as either infusions or decoctions, similar to their traditional utilization. Hedera helix L. (Araliaceae) extended lifespan in worms in a concentration-dependent manner. The mean survival rates in the H. helix-treated groups were significantly higher, by 23.7% when applied at 1000 µg/mL, 16% when applied at 500 µg/mL, and 16% when applied at 250 µg/mL, compared to the control group. HPLC analysis identified chlorogenic acid as the major component of H. helix. Salvia verticillata L. (Lamiaceae) and Myrtus communis L. (Myrtaceae) treatments resulted in median lifespan extension. Maximum lifespan was extended in worms by Rubus sanctus Schreb. (Rosaceae) treatment. This study provided the first evidence demonstrating the possible lifespan-extending effects of a group of Turkish medicinal plants in an in vivo model, C. elegans.