Effects of Estrogen Replacement Therapy on Lipid Peroxidation and Antioxidant Enzyme Activities of Ovariectomized and Ovariectomized-Diabetic Rats

Menopause and diabetes are conditions producing free radicals independently from each other. Estrogen replacement therapy which widely used in postmenopausal period has beneficial effects because of its antioxidant property. The study groups were as follows: ovariectomy (n=8), ovariectomy+17-östradiol (n=8), ovariectomy+diabetes (n=10) and ovariectomy+diabetes+17-östradiol (n=8). Diabetes was induced by streptozotocin (45 mg/kg i.p.) and the treatment with 17-östradiol (0.1 mg/kg/day) was started a week after ovariectomy. After–week long experimental period aortic and uterine tissues were collected from the animals and the malondialdehyde concentration, glutathione peroxidase and catalase activities were quantified. The treatment did not effect blood glucose concentrations, but increased plasma estradiol concentrations. Increased malondialdehyde concentrations were reduced by the treatment in aorta from diabetics and nondiabetics, but the treatment increased malondialdehyde concentrations in nondiabetic uterine while were reducing in diabetic uterine. The treatment also reduced the increased activities of catalase and glutathione peroxidase in aorta from diabetics and nondiabetics, on the other hand the treatment increased the activities of those enzymes in uterine from diabetics and nondiabetics. Our results suggested that estrogen acts as an antioxidant or prooxidant depending on the tissues

Effects of flaxseed intake on vascular contractile function in diabetic rats

In diabetes, one of the most important causes of morbidity and mortality is vasculopathy. Though flaxseed (FXS) is known for improving cardiovascular health, only limited studies are available on FXS concerning diabetic vascular reactivity. Hence, in this study, we studied vascular reactivity changes after FXS treatment on streptozotocin (STZ)-induced diabetic rat aortae. Female Wistar rats were divided into following four groups: control (C), FXS treated (CT), diabetic (D), and FXS treated diabetic (DT) groups. FXS (0,714 g/kg/day; orally) was started after one week of STZ injection and was given for 12 weeks, phenylephrine (Phe)-induced contractions were obtained on isolated aortic rings in the presence of indomethacin, L-NAME and superoxide dismutase (SOD), individually. Phe-responses were increased significantly in D group and completely improved after FXS intake, whereas FXS increased vascular reactivity to Phe in C group. Indomethacin incubation significantly attenuated Phe-induced contractions in all groups of aorta, particularly in D group. L-NAME incubation significantly increased Phe responses in all groups except D group. SOD incubation decreased the contractions efficiently in D group. The decreament was much lower in DT compared to D group, but reverse effects were observed in CT group. Our findings suggest FXS may provide beneficial effects on diabetes-induced vascular reactivity changes through NO and prostaglandin dependent pathways, but in healty condition FXS may have adverse effect probably via pro-oxidant activity

Effects of flaxseed intake on vascular contractile function in diabetic rats

398-405In diabetes, one of the most important causes of morbidity and mortality is vasculopathy. Though flaxseed (FXS) is known for improving cardiovascular health, only limited studies are available on FXS concerning diabetic vascular reactivity. Hence, in this study, we studied vascular reactivity changes after FXS treatment on streptozotocin (STZ)-induced diabetic rat aortae. Female Wistar rats were divided into following four groups: control (C), FXS treated (CT), diabetic (D), and FXS treated diabetic (DT) groups. FXS (0,714 g/kg/day; orally) was started after one week of STZ injection and was given for 12 weeks, phenylephrine (Phe)-induced contractions were obtained on isolated aortic rings in the presence of indomethacin, L-NAME and superoxide dismutase (SOD), individually. Phe-responses were increased significantly in D group and completely improved after FXS intake, whereas FXS increased vascular reactivity to Phe in C group. Indomethacin incubation significantly attenuated Phe-induced contractions in all groups of aorta, particularly in D group. L-NAME incubation significantly increased Phe responses in all groups except D group. SOD incubation decreased the contractions efficiently in D group. The decreament was much lower in DT compared to D group, but reverse effects were observed in CT group. Our findings suggest FXS may provide beneficial effects on diabetes-induced vascular reactivity changes through NO and prostaglandin dependent pathways, but in healty condition FXS may have adverse effect probably via pro-oxidant activity

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

WOS: 000444557200004PubMed ID: 30054861We 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 x 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 alpha 1-adrenergic receptor signaling is activated in both age groups of diabetic rats, diabetes activates K+-depolarization and calcium mobilization via Ca-V 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 (K-Ca), or 4-aminopyridine (4-AP), an inhibitor of voltage-sensitive K+ channels (K-V). 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 K-v and K-Ca 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.Research Foundation of Gazi University [01/2010-126]; Research Foundation of Ankara University [10B336002]; COST Action [BM1203]; Slovak Academy of Sciences [APVV-51-017905]This article has been written by Prof. Karasu who is the leader of ADIC study group. We thank Ahmet Cumaolu and Elif Aydn for their technical help during measurement of some biomarkers. This work originally includes a part of the PhD thesis of Dr. Arzu Sakul and was partly supported by the Research Foundations of Gazi and Ankara Universities (GU-Project No. 01/2010-126, AU-Project No. 10B336002), COST Action BM1203 and the Slovak Academy of Sciences (VEGA grant APVV-51-017905)

NON CHOLESTEROL LOWERING DOSE OF ATORVASTATIN AMELIORATES DIABETIC VENTRICULAR MYOCYTE DYSFUNCTION IN MICE

The aim of this study was to investigate whether atorvastatin ameliorates diabetes-induced cardiomyocyte dysfunction, independently of cholesterol-lowering effect. Streptozotocin-induced diabetic mice were treated with atorvastatin (10 mg/kg, daily, orally) for two weeks. Ventricular cardiomyocytes were isolated and contractile properties including peak shortening (PS), time to PS (TPS), time to 90 % relengthening (TR90) and maximal velocity of shortening/relengthening (+/- dL/dt) were analysed using video-based edge detection. Diabetes caused mechanical dysfunction with dampened stress tolerance of myocytes at high stress frequencies, all of which were significantly alleviated by atorvastatin without affecting hyperglycemia and dyslipidemia. In addition, changes in oxidative stress parameters (CAT activity, GSH and MDA levels) were also normalized by atorvastatin. These data indicate that atorvastatin, independently of its lipid-lowering capacity, reduces myocardial oxidative stress resulting in improved myocyte mechanical function in an experimental model of diabetes. Our results supports the concep