Evaluation of circulating miR-122, miR-30c and miR-33a levels and their association with lipids, lipoproteins in postprandial lipemia.

AIMS: Postprandial lipemia is characterized by an increase in triglyceride-rich lipoproteins after fatty meals. MicroRNAs (miRs) play important roles in lipid and lipoprotein metabolism. The aim of this study was to determine relationship between levels of plasma miR expression and lipoprotein metabolism-related proteins in subjects with normal (NPR) and high postprandial response (HPR) in postprandial period. MATERIALS AND METHODS: The oral fat tolerance test was applied to 22 individuals with NPR and 22 with HPR. KEY FINDINGS: Increased expressions of miR-122 and miR-33a and miR-122/30c ratio and decreased miR-30c expression were observed in fasting and postprandial period of HPR compared with NPR. ROC curve analysis showed that miR-122/30c ratio is a good biomarker for postprandial lipemia (AUC: 0.97, p < 0.001). Levels of TG, MTTP, and Apo B-48 and chylomicron (CM) particle size were significantly higher in HPR than in NPR (p < 0.05). The miR-122/30c ratio at 2 h was positively correlated with CM particle size, and with TG, MTTP and Apo B-48 levels at 4th hour. miR-33a expression decreased in HPR and was negatively correlated with ABCA1 and Apo A-1 levels at 4th hour of the postprandial period in both groups. SIGNIFICANCE: Increased miR-122 and decreased miR-30c expression levels in HPR may play critical roles in elevated or prolonged postprandial lipemia. The miR122/30c ratio exhibited good association with MTTP, Apo B-48 and TG levels, and with CM particle size, and may be a reliable marker for evaluating postprandial lipemia. miR-33a may also play a key role in decreased HDL-C in postprandial lipemia.

Hazelnut consumption improves testicular antioxidant function and semen quality in young and old male rats.

The effects of hazelnut supplemented diet on the reproductive system of young and old male rats were investigated. Young male rats were grouped into young control group (YCG) and young hazelnut group (YHG). Old male rats were grouped into old control group (OCG), old hazelnut group (OHG), and old vitamin E group (OEG). While YCG and OCG were given rat feed, YHG and OHG were given rat feed supplemented with hazelnut (3 g/kg body weight). OEG was subjected to rat feed and administered vitamin E (50 mg/kg body weight). When YCG and OCG were compared, aging increased histopathological damage and decreased sperm quality. Hazelnut supplemented diet improved histopathological variables, sperm quality, seminal plasma and plasma oxidative stress, seminal plasma vitamin E, and plasma testosterone levels in both groups. The present work suggests that hazelnut supplemented diet significantly improves testicular antioxidant function and semen quality in old male rats.

Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy.

PURPOSE: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. METHODS: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. RESULTS: All parameters of neurocognitive development and serum calcium (9.6±0.9 mg/dL vs. 10.4±0.3 mg/dL, p<0.05) and magnesium (2.02±0.27 mg/dL vs. 2.2±0.14 mg/dL, p<0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition (1.33±0.22 vs. 1.18±0.22, p<0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels (p<0.05, r=0.381). CONCLUSION: Calcium supplementation may improve neurocognitive development in malnourished infants.

Relationship between postprandial lipemia and atherogenic factors in healthy subjects by considering gender differences.

BACKGROUND: Postprandial triglyceride concentrations are clinically significant and independent predictor of cardiovascular disease risk. The purpose of this study was to determine postprandial TG ranges in healthy subjects by considering gender differences. Secondly, assess the relationship between postprandial lipemia and atherogenic indicators. Finally, investigate the use of the postprandial 4h TG test instead of the area under the curve (AUC). METHODS: Postprandial lipemia was investigated using the standardized oral fat tolerance test (OFTT) in 96 healthy subjects (45 female/51 male). Study group was categorized into tertiles based on AUC calculated using TG concentrations at fasting and 2, 4 and 6h after OFTT. Lipid, lipoproteins, apolipoproteins, LDL subfractions and oxidized LDL (oxLDL) were evaluated in tertiles in both sex groups. RESULTS: The cut-off concentrations for postprandial 4-hour TG concentrations in female and male were 3.20 mmol/L and 4.59 mmol/L, respectively. We observed higher concentrations for atherogenic indicates like small dense-low density lipoprotein (sdLDL), oxLDL values in top tertiles for both groups (P < 0.05). Cohen's kappa coefficients for the agreement of AUC and 4h postprandial TG tests were 0.935, 0.970, 0.469 (P = 0.0001) in female, male and total study group, respectively. CONCLUSION: Due to predominant effects of gender differences on postprandial lipemia, postprandial TG cut-off values for female and male subjects should be determined separately. Postprandial lipemia may be associated with atherogenic tendency by changing lipids, lipoproteins, sdLDL and oxLDL concentrations, especially in males. Four-hour postprandial TG concentrations emerged as a useful and reliable marker for evaluation of postprandial lipemia.

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.

How does colistin-induced nephropathy develop and can it be treated?

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.

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.

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.

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. METHODS: Twenty-four Sprague-Dawley rats were divided into four groups. The control, GSPE, CsA and CsA+GSPE groups were given 1 mL olive oil, 100 mg/kg GSPE, 25 mg/kg CsA and 100 mg/kg GSPE+25 mg/kg CsA, respectively. On day 21, blood samples were taken for blood urea nitrogen (BUN), creatinine and CsA levels, and renal tissue was used for total oxidant system (TOS), total anti-oxidant system (TAS), oxidative stress index (OSI) and malondialdehyde (MDA) measurements. In addition to renal histopathology, apoptosis staining was performed on renal tissue. RESULTS: The BUN, creatinine, TOS, OSI, MDA, histopathological score, and apoptotic index exhibited increases in the CsA group. In the CsA+GSPE group, however, BUN, creatinine, OSI, MDA, renal histopathological score and apoptotic index (AI) decreased and TAS levels increased. In addition, there was no difference between the CsA and CsA+GSPE groups with regard to CsA levels. CONCLUSION: We demonstrated that GSPE prevents CsA nephropathy and that this effect is achieved by anti-apoptotic and anti-oxidant activity. We also achieved a significant recovery in kidney functions without affecting CsA plasma levels.

Hazelnut consumption decreases the susceptibility of LDL to oxidation, plasma oxidized LDL level and increases the ratio of large/small LDL in normolipidemic healthy subjects.

OBJECTIVE: Nut consumption has beneficial effects on protection for development of atherosclerotic process. METHODS: Single intervention study design was used to determine the effects of hazelnut-enriched diet (1 g/kg/day) during 4 weeks period on atherogenic tendency of low-density lipoprotein (LDL) by evaluating susceptibility of LDL to oxidation, alpha-tocopherol content of LDL, LDL subfractions, plasma oxidized (ox) LDL, lipid and lipoprotein levels in normolipidemic healthy subjects (n=21). Statistical analysis was performed using paired t test, ANOVA for repeated measurements test, Pearson's and Spearman correlation analyses. RESULTS: Lag time for oxidation (baseline 54.6+/- 12.3 min, 15th day 59.3+/- 13.4 min, 30th day 65.2+/- 17.8 min, p=0.001) and ,alpha--tocopherol content of LDL (baseline 4.82+/- 1.2 microg/mg LDL protein, 15th day 4.88+/- 1.4 microg/mg LDL protein, 30th day 5.35+/- 1.7 microg/mg LDL protein, p=0.02) were found to be increased while ox-LDL levels (baseline 57.2+/- 16.2 U/L, 15th day 51.2+/- 13.6 U/L, 30th day 48.2+/- 14.2 U/L, p=0.001) decreased during the study period. Total cholesterol, LDL-cholesterol, apolipoprotein (apo) B and apo B/apo AI ratio were found to be significantly lower while apo AI was higher (p<0.05). In respect to LDL subfraction, ratio of large/small LDL was significantly increased at the end of the study (baseline 3.79+/- 1.35, 15th day 3.41+/- 1.60, 30th day 4.28+/- 2.44, p= 0.046). CONCLUSION: Hazelnut-enriched diet may play important role in decrease in atherogenic tendency of LDL by lowering the susceptibility of LDL to oxidation and plasma ox-LDL levels, and increasing the ratio of large/small LDL beyond its beneficial effect on lipid and lipoprotein levels.