Ebru Sezer

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.

The Effects of Estrogen and Raloxifene Treatment on Antioxidant Enzymes in Brain and Liver of Ovarectomized Female Rats

Recent studies documented that estrogen have antioxidant properties in‐vitro, there are conflicting results on the effect of estrogen in vivo. We aimed to investigate the effects of estradiol and Raloxifene on the antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities and MDA levels in brain and liver homogenates of ovariectomized female rats. Twelve weeks after ovariectomy, female Sprague–Dawley rats (n = 26) were divided into three groups: (1) Ovariectomized placebo group (n = 6) was given physiologic saline. (2) Estrogen group (n = 10) was given Ethynyl estradiol, 0.1 mg/kg sc. (3) Raloxifene group (n = 10) was given raloxifene, 1 mg/kg sc during 8 weeks. Ten rats were used as naive controls without any treatment (Sham operated group, n = 10). Ovariectomy lead to an increase in the CAT activities in liver tissue samples compared to the sham group ( p = 0.056, Mann–Whitney test). While estrogen treatment reversed to normal levels of CAT activities, raloxifene remained as ineffective. Superoxide dismutase activities and MDA levels in liver were remained unchanged in all groups. There was no significant change in the brain tissue SOD and CAT activities between the control, ovariectomy, estrogen treated, and raloxifen treated groups. We determined an increase in MDA levels in brain of ovariectomised rat ( p = 0.02). While raloxifene treatment reversed to normal levels of MDA ( p = 0.008), estrogen treatment failed. Our data showed that estrogen may play a role in regulation of CAT and SOD activities in liver due to its antioxidative effects. We can suggest that estrogen and raloxifene exert their antioxidative effects in brain rather than liver. Since Raloxifenes effect is more clear than estradiol, raloxifene may be suggested primarily for treatment and/or prevention of diseases which can be resulted from oxidative stress in postmenopausal women.

Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis.

Although doxorubicin (DOX) is a commonly used chemotherapeutic agent its clinical use is restricted due to its organ toxicities. The present investigation relates to reducing DOX induced side effects to the liver, kidney and ileum by usage of the antioxidant, anti-inflammatory agent, resveratrol (RES) and to investigate the role of nitric oxide synthase (NOS) in the process. Wistar rats were divided into four groups: control (saline i.p); DOX (20 mg/kg i.p), RES (20 mg/kg i.p) and DOX (20mg/kg i.p)+RES (20 mg/kg i.p). Immunohistochemical activity of both iNOS and eNOS were evaluated after DOX treatment and ultrastructural changes such as cellular damage and mitochondrial degeneration were evaluated. Degenerative ultrastructural changes were demonstrated especially in the DOX treated group. Variations in biochemical marker levels of oxidative stress on ischemia in tissues were not observed. Our data indicate that RES may prevent cellular damage in the early phase of DOX induced toxicity. RES could be used with its beneficial effects during early cellular damage in organ toxicity after DOX treatment in cancer patients.

The effects of estrogen and raloxifene treatment on the antioxidant enzymes and nitrite-nitrate levels in brain cortex of ovariectomized rats

Number of studies indicate that the female gonadal hormone estrogen protects women against several neurodegenerative diseases and cerebral ischemia via various mechanisms. The possible protective effects of estrogen are mediated mainly by three ways; the activation of steroid receptors and/or modulation of a neurotransmitter and/or direct antioxidative action. Therefore we aimed to investigate the effects of estradiol and raloxifene on levels of nitric oxide (NO) and antioxidant enzymes in brain cortex of ovariectomized female rats. Ten Sprague-Dawley rats were used as naive controls while 32 rats were ovariectomized at 120-140 days of age. Twelve weeks after ovariectomy: (1). Ovariectomized Placebo group (n=11), was given physiologic saline. (2). Estrogen group (n=10) was given Ethynyl estradiol, 0.1 mg/kg sc. (3). Raloxifene group (n=10) was given raloxifene, 1 mg/kg sc. At the end of the treatment period (8 weeks), rats were decapitated and cortex samples were dissected. Results showed that ovariectomy caused a decrease in total nitrite-nitrate levels. The NO levels of both the estrogen and the raloxifene group were higher than the placebo group. Catalase activities did not show any significant difference between the groups, while superoxide dismutase (SOD) activities were elevated via ovariectomy. Estradiol and Raloxifene treatment had no statistically significant effect on SOD activity.

Effect of atorvastatin therapy on oxidant-antioxidant status and atherosclerotic plaque formation.

Background: The aim of this study was to determine the oxidant–antioxidant status and lipid peroxidation products, as well as paraoxonase and atherosclerotic plaque formation, in a hypercholesterolemic atherosclerosis rabbit model to investigate the effects of atorvastatin in the atherosclerotic process. Methods: Forty male New Zealand rabbits were divided into four groups, ie, a control group receiving standard pellets, a group receiving atorvastatin therapy, a hypercholesterolemic group receiving an atherogenic diet, and a group receiving both an atherogenic diet and atorvastatin. Results: The atherogenic diet increased the levels of low-density lipoprotein (LDL) thiobarbituric acid reactive substances (1.84 vs 3.79 nmol/mg protein) and LDL-conjugated diene (147 vs 318 μmol/mg protein) after induction of oxidation by Cu2+, despite an increase of superoxide dismutase activity. Treatment with atorvastatin limited LDL oxidation significantly (LDL thiobarbituric acid reactive substances 2.19 nmol/mg protein, LDL-conjugated diene 222 μmol/mg protein). Paraoxonase, which prevents LDL oxidation and inactivates LDL-derived oxidized phospholipids, showed a pronounced decrease in the group receiving the atherogenic diet (110 U/L to 28 U/L), and atorvastatin treatment increased paraoxonase activity. Histological examination of arcus aorta tissues from the hypercholesterolemic group showed abundant plaque formation surrounding and obstructing the lumen, whereas treatment with atorvastatin prevented or limited plaque formation, keeping the plaque thin and localized. Conclusion: Atorvastatin has dramatic antiatherosclerotic effects, part of which seems to be due to the antioxidant features of the parent drug and/or its metabolites, favoring inhibition of LDL oxidation.

Alterations in l -arginine and inflammatory markers in type 2 diabetic patients with and without microalbuminuria

Low-grade inflammation is closely involved in the pathogenesis of type 2 diabetes and associated micro- and macrovascular complications. The nitric oxide (NO) precursor l-arginine, is relevant to diverse pathological conditions including type 2 diabetes and its complications. High sensitive-CRP (hs-CRP), neopterin and arginine levels were measured in 46 normoalbuminuric, 45 microalbuminuric type 2 diabetics and in 32 healthy controls in order to assess the relationship between markers of inflammation and l-arginine. Hs-CRP concentrations were higher in microalbuminuric diabetic patients compared to normoalbuminuric patients and controls. Diabetics had higher serum and urine neopterin levels than controls. Urine neopterin and l-arginine levels differed significantly among diabetic patients with and without microalbuminuria. There were significant positive correlations between hs-CRP and BMI in healthy controls and diabetics with and without microalbuminuria. In microalbuminuric diabetics, hs-CRP correlated with microalbuminuria (MAU). Significant predictors for the development of microalbuminuria were higher postprandial glucose levels, lower creatinine clearance and lower serum l-arginine levels. Assessment of early markers of inflammation and endothelial function, such as neopterin and NO precursor l-arginine, may help to predict incipient nephropathy more accurately in type 2 diabetic patients.

Infertility and the Presence of Insulin Resistance Are Associated With Increased Oxidative Stress in Young, Non-obese Turkish Women With Polycystic Ovary Syndrome

STUDY OBJECTIVE To investigate the relationship between both insulin resistance and fertility and the oxidant/antioxidant system in young, non-obese patients diagnosed with polycystic ovary syndrome (PCOS). DESIGN Case-control study. SETTING Department of Obstetrics and Gynecology, Ege University, Izmir, Turkey. PARTICIPANTS PCOS patients without insulin resistance (IR-) (n = 33), PCOS patients with insulin resistance (IR+) (n = 27), and healthy controls (n = 30). Patients with PCOS and regular sexual intercourse were further divided into infertile (n = 14) and fertile (n = 15) groups. MAIN OUTCOME MEASURES The malondialdehyde (MDA) and thiol levels as well as the catalase (CAT) and superoxide dismutase (SOD) enzyme activities. RESULTS Both IR+ and IR- PCOS patients had higher MDA levels and lower thiol levels when compared to the controls (each P < .001). However, only IR- patients had significantly higher SOD (3700.81 ± 410.13 vs 2614.19 ± 611.80 U/g Hb; P < .001) and CAT (7565.06 ± 628.27 vs 6819.61 ± 539.2 U/g Hb; P < .001) activities when compared to the controls. Infertile PCOS patients had significantly higher MDA levels (347.5 ± 22.8 vs 278.6 ± 42.6 nmol/g Hb, P < .001) and lower thiol levels (498.5 ± 56.2 vs 568.5 ± 38.6 μmol/l, P = .001) when compared to fertile patients. CONCLUSIONS The results of this study demonstrated an imbalance in the oxidative-antioxidative system of PCOS patients. This imbalance was worse in IR+ and infertile PCOS patients.

Neuroprotective effects of melatonin upon the offspring cerebellar cortex in the rat model of BCNU-induced cortical dysplasia

Cortical dysplasia is a malformation characterized by defects in proliferation, migration and maturation. This study was designed to evaluate the alterations in offspring rat cerebellum induced by maternal exposure to carmustine-[1,3-bis (2-chloroethyl)-1-nitrosoure] (BCNU) and to investigate the effects of exogenous melatonin upon cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses. Pregnant Wistar rats were assigned to five groups: intact-control, saline-control, melatonin-treated, BCNU-exposed and BCNU-exposed plus melatonin. Rats were exposed to BCNU on embryonic day 15 and melatonin was given until delivery. Immuno/histochemistry and electron microscopy were carried out on the offspring cerebellum, and levels of malondialdehyde and superoxide dismutase were determined. Histopathologically, typical findings were observed in the cerebella from the control groups, but the findings consistent with early embryonic development were noted in BCNU-exposed cortical dysplasia group. There was a marked increase in the number of TUNEL positive cells and nestin positive cells in BCNU-exposed group, but a decreased immunoreactivity to glial fibrillary acidic protein, synaptophysin and transforming growth factor beta1 was observed, indicating a delayed maturation, and melatonin significantly reversed these changes. Malondialdehyde level in BCNU-exposed group was higher than those in control groups and melatonin decreased malondialdehyde levels in BCNU group (P<0.01), while there were no significant differences in the superoxide dismutase levels between these groups. These data suggest that exposure of animals to BCNU during pregnancy leads to delayed maturation of offspring cerebellum and melatonin protects the cerebellum against the effects of BCNU.

The Effect of Melatonin on a Dorsal Skin Flap Model

ABSTRACT Background: Melatonin (Mel) has a very potent antioxidant activity, depending mainly on its capacity to act as an electron donor. Recently, the antioxidant property of Mel has been much emphasized. In this study, the dorsal skin flap model was used to investigate the effect of Mel in flap viability in rats. Material and Methods: Totally 28 Wistar Albino rats were divided into four groups: control group (C) (n = 7), local treatment group (L) (n = 7), systemic low-dose melatonin treatment group (LT) (n = 7), and systemic high-dose melatonin treatment group (HT) (n = 7). The necrosis rate of the skin flaps was observed seven days after the operation by a blinded observer. Oxidative stress was assessed by determining malondialdehyde (MDA) level, and effects of melatonin on antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were measured. Vascularity, epithelial thickness, and fibroblast proliferation of dorsal skin flaps were assessed histologically. Results: Amount of MDA were found significantly lower (p < .05), and the flap viability, CAT, SOD, vascularity, fibroblast proliferation, and epithelial thickness were found significantly higher (p < .05) in groups HT than in groups C, L, and LT statistically. Conclusion: Our results showed that the usage on different doses of melatonin could play an important role in the process of flap viability and further studies will focus on these areas of interest.

The report of the 1st Turkey in vitro diagnostic symposium results

Abstract “The 1st Turkish in vitro Diagnostic Symposium” was organized in İzmir between the dates 18–20 February 2016 with cooperation of Turkish Biochemistry Society Izmir Branch and Dokuz Eylul University Institute of Health Sciences. This article presents a collection of the subjects, recommendations and results included in the final report of the symposium. Symposium subjects were analysed under separate titles and evaluated together with results obtained from various reports on medical devices (MD) in the last decade. According to the final report, the subjects to be considered on preferential basis include “configuration of the websites of legal authorities, standardization and accreditation institutions in a way to access work on in vitro Diagnostic (IVD)”, “activation of university-industry cooperation”, “determination of national standards parallel to international standards” and “carrying out the statistics about IVD-MD in Turkey as immediate as possible”. Drawing attention to the fact that there is a requirement for competent man power for every-stage of IVD-MD lifecycle, it is recommended that postgraduate education programmes are founded to serve these fields. Consequently, this symposium enabled to determine the basic problems about the sector by bringing together the stakeholders related to IVD-MD field and to come up with an action plan in accordance with the recommendations.