Fulya Balaban Yucesan

Hazelnut-enriched diet improves cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects

BACKGROUND Tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. However, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. METHODS The antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. Twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. These were control diet I (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18%-20% of the total daily energy intake), and control diet period II (4 weeks). The cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (FMD) technique, low-density lipoprotein (LDL) oxidation products and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (sVCAM-1) as well as lipids and lipoprotein levels were monitored. RESULTS Consumption of a hazelnut-enriched diet significantly improved FMD (56.6%), total cholesterol (-7.8%), triacylglycerol (-7.3%), LDL-cholesterol (-6.17%), and high-density lipoprotein cholesterol (6.07%) compared with the control diet I. Oxidized-LDL, hs-CRP, and sVCAM-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets I and II. Modest correlations between sVCAM-1 and FMD and between sVCAM-1 and hs-CRP were observed (r = -0.49, P < .025; r = 0.66, P < .001, respectively). CONCLUSION Hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing LDL oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. These beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. Therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit.

Effect of Turkish propolis extracts on proteome of prostate cancer cell line

BackgroundPropolis is a natural, resinous hive product that has several pharmacological activities. Its composition varies depending on the vegetation, climate, season and environmental conditions of the area from where it was collected. Surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) is a proteomic approach which has been used in cancer proteomics studies. Prostate cancer is one of the most commonly diagnosed cancers in men. It has shown that nutritional supplements rich in polyphenolic compounds such as propolis play a significant role in prostate cancer chemoprevention. The aim of this study is to evaluate if protein expression profile in PC-3 prostate cancer cell lines could be differentiated when incubated with dimethyl sulfoxide and water extracts of Turkish propolis.ResultsThe antioxidant potentials of dimethyl sulfoxide and water extracts of propolis were found in correlation with the amount of total phenolic compounds of them. Dimethyl sulfoxide and water extracts of propolis of 20 μg/mL reduced the cell viability to 24.5% and 17.7%, respectively. Statistically significant discriminatory peaks between control PC-3 cells and dimethyl sulfoxide extract of propolis-treated PC-3 cells were found to be the proteomic features at m/z 5143, 8703, 12661, 20184 and 32794, detected by CM10 ProteinChip, and the peak at m/z 3772, detected by Q10 ProteinChip. Between control PC-3 cells and water extract of propolis-treated PC-3 cells, statistically significant discriminatory peaks were found to be the proteomic features at m/z 15846, 16052 and 24658, detected by CM10 ProteinChip and the peaks at m/z 10348, 10899 and 11603, detected by Q10 ProteinChip.ConclusionsIt was concluded that dimethyl sulfoxide and water extracts of Turkish propolis may have anti-proliferative activity through differentiating protein expression profile in PC-3 prostate cancer cell lines along with their antioxidant capacity.

Anti‐apoptotic and anti‐oxidant effects of grape seed proanthocyanidin extract in preventing cyclosporine A‐induced nephropathy

Aim:  Although the pathogenesis of cyclosporine (CsA) nephropathy is not completely understood, it is attributed to oxidative damage and apoptosis. Grape seed proanthocyanidin extract (GSPE) is a molecule with anti‐oxidant and anti‐apoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing CsA nephropathy.

How Does Colistin-Induced Nephropathy Develop and Can It Be Treated?

ABSTRACT Colistin is an old antibiotic used in the treatment of Gram-negative infections. It was once suspended because of its nephrotoxic effect but has since been reintroduced due to multidrug-resistant bacterial infections. The pathogenesis of colistin-associated nephropathy has not been clarified, and there is currently no effective therapeutic or prophylactic agent available. The aim of this study was to investigate the roles of caspase-associated apoptosis and caspase 1, calpain 1, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) expression in the pathogenesis of colistin-associated nephrotoxicity and the effect of grape seed proanthocyanidin extract (GSPE) in preventing it. Twenty-four rats were divided into three groups: control, colistin, and colistin plus GSPE (colistin+GSPE). Colistin-associated nephropathy was induced by the administration of 300,000 IU/kg of body weight/day colistin intraperitoneally for 7 days. The experiment was discontinued on the seventh day. Blood was collected for measurements of blood urea nitrogen (BUN) and creatinine levels. Histopathological examination of kidney tissue and caspase 1 and 3, iNOS, eNOS, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and calpain 1 staining was also performed. Significant increases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed for the colistin group compared to the control group. Significant decreases in BUN levels; creatinine levels; renal histopathological scores; and TUNEL, caspase 1 and 3, calpain 1, iNOS, and eNOS staining were observed in the colistin+GSPE group compared to the colistin group. Our study shows, for the first time in the literature, that caspase-mediated apoptosis, iNOS, caspase 1, and calpain 1 are involved in the pathogenesis of colistin-associated nephropathy. GSPE had a renoprotective effect, as shown by the lowered levels of these mediators.

Protective Effect of the Grape Seed Proanthocyanidin Extract in a Rat Model of Contrast-Induced Nephropathy

Aim: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. Materials and Methods: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. Conclusion: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.

The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy.

Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

GSPE is superior to NAC in the prevention of contrast-induced nephropathy: Might this superiority be related to caspase 1 and calpain 1?

AIMS Our study was intended to evaluate the role of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), caspases 1 and 3 and calpain 1 in the pathogenesis of contrast-induced nephropathy (CIN) and to compare the protective effects of N acetyl cysteine (NAC) and grape seed proanthocyanidin extract (GSPE) against the development of CIN. MAIN METHODS 32 rats were divided into four groups; control, contrast media (CM), CM+NAC and CM+GSPE. CIN was induced by administration of 7 ml/kg diatrizoate. The experiment was discontinued on the ninth day. Blood was collected for blood urea nitrogen (BUN) and creatinine measurement. Rat kidney tissues were removed for histopathological evaluation and the investigation of caspases 1 and 3, iNOS, eNOS, TUNEL and calpain 1. KEY FINDINGS A significant increase in BUN, creatinine, renal histopathological injury, TUNEL, caspases 1, 3, calpain 1, iNOS and eNOS was observed in the CM group compared to the control group. There was amelioration in all these parameters in the CM+GSPE group, while there was no significant amelioration in BUN, creatinine and renal histopathological injury in the CM+NAC group. In addition, calpain 1 staining and creatinine were significantly lower in the CM+GSPE group compared to the CM+NAC group. SIGNIFICANCE Our study showed, for the first time in the literature, that GSPE has a greater renoprotective effect compared with NAC and that this effective protection may be related to decrease in calpain 1 levels.

The effect of grape seed proanthocyanidin extract in preventing amikacin-induced nephropathy

Background/Aims: Nephrotoxicity induced by aminoglycosides (AGs) limits their clinical use. As yet, no molecules have been approved to prevent AG nephropathy. We aim to investigate the effectiveness of grape seed proanthocyanidin extract (GSPE) in the prevention of amikacin (AK)-induced nephrotoxicity. Methods: A total of 24 rats were allocated into control, GSPE, AK, and AK + GSPE groups. While 1 mL saline was administered for 6 days in control and AK groups, 100 mg/kg GSPE was administered in GSPE and AK + GSPE groups. On day 7, intraperitoneal (i.p.) saline was administered in control and GSPE groups, while 1.2 g/kg i.p. AK was administered in AK and AK + GSPE groups. The experiment was terminated on day 9. Blood samples were taken for the measurement of renal functions. Renal tissues of the rats were removed for the analysis of malondialdehyde (MDA), total oxidant system (TOS), total antioxidant system, oxidative stress index (OSI), and for histopathological examination. Results: MDA level was found to be lower in GSPE group compared with other study groups. There was significantly more renal histopathological damage and higher blood urea nitrogen, creatinine, TOS, OSI, and MDA levels in the AK group compared with the control and AK + GSPE groups. The same parameters showed significant improvement in AK + GSPE group compared with AK group. Conclusion: Our findings demonstrate for the first time that GSPE reduces oxidative damage in AK nephropathy and provides biochemical and renal histopathological improvements.

Effects of glutamine on wound healing.

Studies reporting the need for replacing amino acids such as glutamine (Gln), hydroxymethyl butyrate (HMB) and arginine (Arg) to accelerate wound healing are available in the literature. The primary objective of this study was to present the effects of Gln on tissue hydroxyproline (OHP) levels in wound healing. This study was conducted on 30 female Sprague Dawley rats with a mean weight of 230 ± 20 g. Secondary wounds were formed by excising 2 × 1 cm skin subcutaneous tissue on the back of the rats. The rats were divided into three equal groups. Group C (Control): the group received 1 ml/day isotonic solution by gastric gavage after secondary wound was formed. Group A (Abound): the group received 0·3 g/kg/day/ml Gln, 0·052 g/kg/day/ml HMB and 0·3 g/kg/day/ml Arg by gastric gavage after secondary wound was formed. Group R (Resource): the group received 0·3 g/kg/day/ml Gln by gastric gavage after secondary wound was formed. The OHP levels of the tissues obtained from the upper half region on the 8th day and the lower half region on the 21st day from the same rats in the groups were examined. Statistical analysis was performed using the statistics program SPSS version 17.0. No statistically significant differences were reported with regard to the OHP measurements on the 8th and 21st days (8th day: F = 0·068, P = 0·935 > 0·05; 21st day: F = 0·018, P = 0·983 > 0·05). The increase in mean OHP levels on the 8th and 21st days within each group was found to be statistically significant (F = 1146·34, P = 0·000 < 0·001). We conclude that in adults who eat healthy food, who do not have any factor that can affect wound healing negatively and who do not have large tissue loss at critical level, Gln, Arg and HMB support would not be required to accelerate secondary wound healing.

Increased plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are related to good collateral development in patients with isolated left coronary artery disease

Development of coronary collaterals (CCs) is a time-dependent adaptive response to an ischemic process arising from the gradient between obstructed arteries and myocardial ischemia. It is a complex inter-relationship among various factors [1]. A complex interaction exists between new blood vessel formation and inflammation. However, little data are available on the relation between inflammation and the development of CCs [2,3]. Inflammation has emerged as central to the initiation and progression of atherosclerosis. The mechanism(s) underlining collateral artery growth closely resemble those of atherosclerosis. Lipoprotein-associated phospholipase A2(Lp-PLA2) is actively secreted by monocyte-derived macrophages in atherosclerotic plaque. Lp-PLA2 is a unique inflammatory biomarker, as it is highly vascular specific, has low biologic variability, and is directly related to the propensity of plaque rupture and the degree of inflammation present in the walls of coronary arteries [4]. The inflammatory process is also associatedwith an increased oxidant environment. In a recent study, it was indicated that oxidative stress may also play an important role in the development of CCs [5]. Ischemia modified albumin (IMA), the earliest ischemic marker, in atherosclerosis has been extensively studied, but, there is no data on the possible involvement of Lp-PLA2 and IMA in the development of coronary collaterals. In this prospective preliminary study, it was aimed to investigate the possible role and involvement of plasma Lp-PLA2, IMA and oxidant stress status in patients with isolated left coronary artery disease (CAD). This prospective study was conducted between January 2007 and September 2009 in our university hospital setting. Clinical indications were considered in all patients undergoing coronary angiography by using the standard femoral approach by the Judkins technique. Because the multi-vessel coronary disease has a significant influence on the development of collaterals, we mainly evaluated the single-vessel disease group, with ≥90% narrowing or total occlusion of the left anterior descending (LAD) and nonsignificant (b30%) narrowing of the non-LAD (5). The study was approved by the local Ethics Committee. Coronary collateral development was graded according to the Cohen– Rentrop method [6]. Classification of the patients according to the Rentrops score yielded 24 of patients with poor developed CCs, (Rentrops score of 0 to 1), and 21 had good developed CCs (Rentrops score of 2 to 3). The Gensini score was computed for each patient from the coronary arteriogram by assigning a severity score to each coronary stenosis [7]. The levels of serum total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDLC) were determined by enzymaticmethods using a ROCHE autoanalyzer (Modular System,GmbH,Mannheim,Germany). hs-CRPwas assessed by the latex enhanced immunonephelometric method (DADE BEHRING, GmbH, Marburg, Germany). Lp-PLA2 concentration (mass) was measured by a turbidimetric immunoassay method (PLAC® test, diaDexus). Lp-PLA2 activity was measured in an autoanalyzer (Roche, Cobas-6000). The inter-assay coefficient of variation (CV) was 6.2%. Serum total antioxidative capacity (TAC), total oxidant status (TOS) and Oxidative Stress Index (OSI) were assayed as described previously [8]. Inter-assay CVswere 2.5% and 3.1% respectively. The IMA level was assayed by using Bar-Or et al.s method [9]. The results were reported as absorbance units (AbsUs). Inter-assay CV was 4.2%. Of the inflammation markers, Lp-PLA2 was found to be significantly higher in patients with good CCs thanwith poor CCs (pb0.020) while hs-CRP was lower in patients with good CCs thanwith poor CCs. The results of the present prospective study demonstrated that Lp-PLA2 has an independent association with good coronary collateral development andwithGensini score in patientswith isolated left coroner artery involvement. This is the first report investigating the plasma Lp-PLA2 level in coronary collateral development. Lp-PLA2 plays a pivotal role for inflammatory progress of the atherosclerotic process [10]. Lp-PLA2 is a unique inflammatory biomarker, as it is highly vascular specific, and has low biologic variability compared to the hs-CRP (4). Little data are available on the relation between inflammation and the development of CCs [11]. In those studies, authors showed an inverse relationship between CRP and coronary collateral development. Similar distribution of the CRP level between poor and good CC groups was observed in the