Elevated hippocampal mGlut2 receptors in rats with metabolic syndrome-induced-memory impairment, possible protection by vitamin D.

BACKGROUND: Metabolic syndrome patients are commonly prone to major health problems as cardiovascular diseases, diabetes mellitus, chronic kidney disease, cancer and neuropsychological complications including dementia. OBJECTIVES: This research investigates mechanisms linking metabolic syndrome to cognitive impairment and possible impact of vitamin D supplementation. METHODS: Forty male Wistar rats were divided into 4 groups. Control, metabolic syndrome (20% fructose solution in drinking water for 12 weeks, vitamin D supplemented (500 IU/kg/day)) and metabolic syndrome supplemented with vitamin D. Animals were assessed for spatial memory, hippocampal expression of SNAP 25, VAMP and mGlut2 receptor and hippocampus histological examination. Animals with metabolic syndrome showed prolonged acquisition and retention latencies in morris water maze, decreased hippocampal expression of SNAP 25 and VAMP and increased mGlut2 expression. Histologically CA1, CA3 regions and dentate nucleus revealed increase in degenerated neurons and glia cells with decreased pyramidal cell layer thickness. Vitamin D supplementation mitigated alterations induced by metabolic syndrome. CONCLUSIONS: Metabolic syndrome decreased hippocampal synaptic proteins and altered glutamatergic transmission and increased hippocampal neuronal degeneration. Vitamin D supplementation offered neuroprotective effects.

Uncoupling proteins: are they involved in vitamin D3 protective effect against high-fat diet-induced cardiac apoptosis in rats?

This study aimed to assess the impact of high-fat diet (HFD) and vitamin D3 supplementation on cardiac apoptosis, inflammation, oxidative stress, and cardiac uncoupling proteins (UCPs) 2&3 expression. Forty rats were fed either (45%) or (10%) fat diet with or without vitamin D3 (500 U/kg/day) for 6 months, then cardiac tissue expression of Bax, Bcl2, Fas, Fas-L (markers for apoptotic pathways), TNF-α, MDA7, GPX1 (inflammatory and oxidative markers) and UCP 2&3 were assessed. Results revealed the enhancement of intrinsic and extrinsic cardiomyocyte apoptosis cascades and increased inflammatory and oxidative burdens on the heart in HFD rats. Downregulation of UCP2 and upregulation of UCP3 gene expression at 6 months. After vitamin D3 supplementation with HFD, cardiac apoptotic, inflammatory and oxidative markers were mitigated and expression of UCP3 was downregulated and UCP2 was upregulated. This work highlights the novel cardioprotective effect of vitamin D3 in the experimental model of HFD feeding through the downregulation of UCP3.

Efficacy of oral agar in management of indirect hyperbilirubinemia in full-term neonates.

AIM: This prospective randomized case control study aimed to investigate effect of oral agar administration in reducing total serum bilirubin (TSB) levels in full-term neonates with jaundice in comparison with control. MATERIALS AND METHODS: One hundred sixty full-term neonates were enrolled with TSB 10-19 mg/dl at first week of age from Assiut University Children's Hospital. Neonates were divided according to TSB into outpatient group (n = 100) (TSB 10-15 mg/dl) and admitted group (n = 60) (TSB > 15-19 mg/dl). Outpatients group were subdivided into agar group received oral agar and control group received placebo. Admitted group were subdivided into agar group received oral agar plus phototherapy combination and control group received phototherapy alone. Neonates in the agar supplementation received oral agar 600 mg/kg/day dissolved in 10 ml distilled water twice daily till TSB decreased to 7 mg/dl. Daily weight, stool frequency and side effects of treatment were observed for each group. TSB was determined pretreatment then serially every 48 h until TSB level reaching ≤7 mg/dl. RESULTS: Agar fed was effective in lowering TSB in neonates with TSB 10-15 mg/dl. TSB percentage changes were not significantly lower in agar-fed newborn with TSB >15-19 mg/dl compared with control groups after 24 h and 7 days. Age fed shortened the time required to decrease TSB and increased stooling frequency. CONCLUSIONS: Oral agar supplemented feeding at 600 mg/kg/day is safe for full-term neonates and useful in decreasing TSB and phototherapy duration. The efficacy of phototherapy in decreasing TSB level in neonatal hyperbilirubinemia can be augmented with oral agar usage.

Parathormone--25(OH)-vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: Skeletal involvement in patients with type 1 diabetes mellitus (T1DM) has complex pathogenesis and despite numerous researches on this problem, many questions remain unanswered. OBJECTIVE: This study aimed to assess bone status by measurement parathormone (PTH), 25-hydroxy vitamin D [25(OH)D] serum levels in children and adolescents with T1DM and its relation to insulin-like growth factor-1 (IGF-1), disease duration, puberty stage, and metabolic control. PATIENTS AND METHODS: This study included 36 children and adolescents with T1DM and 15 apparently healthy controls. Serum levels of 25(OH)D, PTH, IGF-1 measured using enzyme-linked immunosorbent assay (ELISA), while glycosylated hemoglobin (HbA1c), calcium (Ca), inorganic phosphorus (PO(4) ) using autoanalyzer. Bone quality assessed using dual energy X-ray absorptiometry (DEXA). RESULTS: Diabetic patients showed significant increase in PO(4) and PTH levels, while significant decrease in Ca, IGF-1, and 25(OH)D serum levels. As much as 52.8% of patients showed reduced 25(OH)D, and 30.65% showed elevated PTH serum levels. In diabetic patients, abnormal bone status (osteopenia-osteoporosis) found mostly in total body (94.40%) then lumber-spine (88.90%), ribs (88.90%), pelvis (86.10%), thoracic-spine (80.60%), arms (80.60%) and legs (77.80%), while head bones showed no abnormalities. Long diabetic duration had negative; meanwhile PTH, onset age, and puberty age had positive impact on bone status. CONCLUSIONS: Children and adolescent with T1DM have abnormal bone status mostly in axial skeleton which may be contributed to impairment of formation of 25(OH)D and IGF-1. Physical activity, calcium and vitamin D supplement seem important in T1DM. Elevated serum PTH level in diabetic patients is not uncommon and its positive correlation with bone status needs further investigations.

Protective effect of green tea on lead-induced oxidative damage in rat's blood and brain tissue homogenates.

Recent studies have shown that lead (Pb) could disrupt tissue prooxidant/antioxidant balance which lead to physiological dysfunction. Natural antioxidants are particularly useful in such situation. Current study was designed to investigate efficacy of green tea extract (GTE), on oxidative status in brain tissue and blood caused by chronic oral Pb administration in rats. Four groups of adult male rats (each 15 rats) were utilized: control group; GTE-group (oral 1.5% w/v GTE for 6 weeks); Pb-group (oral 0.4% lead acetate for 6 weeks), and Pb+GTE-group (1.5% GTE and 0.4% lead acetate for 6 weeks). Levels of prooxidant/antioxidant parameters [lipid peroxides (LPO), nitric oxides (NO), total antioxidant capacity (TAC), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD)] in plasma, erythrocytes, and brain tissue homogenate were measured using colorimetric methods. Pb concentrations in whole blood and brain tissue homogenate were measured by atomic absorption. In Pb-group, levels of LPO were higher while NO and GSH were lower in plasma, erythrocytes, and brain tissue than controls. TAC in plasma, SOD in erythrocytes, and GST in brain tissue homogenate were lower in Pb-group versus control. GTE co-administrated with Pb-reduced Pb contents, increased antioxidant status than Pb-group. In erythrocytes, Pb correlated positively with LPO and negatively with NO, GSH, SOD, and Hb. In brain tissue homogenate, Pb correlated positively with LPO and negatively with GSH. This study suggests that lead induce toxicity by interfering balance between prooxidant/antioxidant. Treatment of rats with GTE combined with Pb enhances antioxidant/ detoxification system which reduced oxidative stress. These observations suggest that GTE is a potential complementary agent in treatment of chronic lead intoxication.

Protective effect of green tea on lead-induced oxidative damage in rat’s blood and brain tissue homogenates

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Recent studies have shown that lead (Pb) could disrupt tissue prooxidant/antioxidant balance which lead to physiological dysfunction. Natural antioxidants are particularly useful in such situation. Current study was designed to investigate efficacy of green tea extract (GTE), on oxidative status in brain tissue and blood caused by chronic oral Pb administration in rats. Four groups of adult male rats (each 15 rats) were utilized: control group; GTE-group (oral 1.5% w/v GTE for 6 weeks); Pb-group (oral 0.4% lead acetate for 6 weeks), and Pb+GTE-group (1.5% GTE and 0.4% lead acetate for 6 weeks). Levels of prooxidant/antioxidant parameters [lipid peroxides (LPO), nitric oxides (NO), total antioxidant capacity (TAC), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD)] in plasma, erythrocytes, and brain tissue homogenate were measured using colorimetric methods. Pb concentrations in whole blood and brain tissue homogenate were measured by atomic absorption. In Pb-group, levels of LPO were higher while NO and GSH were lower in plasma, erythrocytes, and brain tissue than controls. TAC in plasma, SOD in erythrocytes, and GST in brain tissue homogenate were lower in Pb-group versus control. GTE co-administrated with Pb-reduced Pb contents, increased antioxidant status than Pb-group. In erythrocytes, Pb correlated positively with LPO and negatively with NO, GSH, SOD, and Hb. In brain tissue homogenate, Pb correlated positively with LPO and negatively with GSH. This study suggests that lead induce toxicity by interfering balance between prooxidant/antioxidant. Treatment of rats with GTE combined with Pb enhances antioxidant/ detoxification system which reduced oxidative stress. These observations suggest that GTE is a potential complementary agent in treatment of chronic lead intoxication (AU)

Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study.

BACKGROUND: In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies mainly in adult demonstrating renal involvement in beta-thalassemia. This prospective study was aimed to investigate renal involvement in pediatric patients with transfusion dependent beta-thalassemia major (TD-betaTM), using both conventional and early markers of glomerular and tubular dysfunctions, and to correlate findings to oxidative stress and iron chelation therapy. METHODS: Sixty-nine TD-betaTM patients (aged 1-16 years) and 15 healthy controls (aged 3-14 years) were enrolled in this study. Based on receiving chelation therapy (deferoxamine, DFO), patients were divided into two groups: group [I] with chelation (n=34) and group [II] without chelation (n=35). Levels of creatinine (Cr), calcium (Ca), inorganic phosphorus (PO4), uric acid (UA) and albumin were measured by spectrophotometer. Serum (S) levels of cystatin-C (SCysC) and total antioxidant capacity (STAC) and urinary (U) levels of beta2-microglobulin (Ubeta2MG) were measured by immunosorbent assay (ELISA). Urinary N-acetyl-beta-D-glucosaminidase (UNAG) activity and malondialdehyde (UMDA) were measured by chemical methods. Estimated glomerular filtration rate (eGFR) was determined from serum creatinine. RESULTS: In patient with and without chelation, glomerular [elevated SCysC, SCr, Ualbumin/Cr and diminished eGFR]; and tubular dysfunctions [elevated SUA, SPO4, UNAG/Cr, Ubeta2MG/Cr] and oxidative stress marker disturbances [diminished STAC and elevated UMDA/Cr] were reported than controls. In patients with chelation, SCysC was significantly higher while, STAC was significantly lower than those without chelation. In all patients, SCysC showed significant positive correlation with SCr and negative correlation with eGFR; STAC showed significant positive correlation with eGFR and negative correlation with SCysC, SCr, UNAG/Cr; UMDA/Cr showed significant positive correlation with Ualbumin/Cr, Ubeta2MG/Cr, UNAG/Cr. CONCLUSIONS: Our data confirm high frequency of glomerular and tubular dysfunctions in TD-betaTM pediatric patients which could be attributed to oxidative stress and DFO therapy.

Iron chelation therapy in Upper Egyptian transfusion-dependent pediatric homozygous beta-thalassemia major: impact on serum L-carnitine/free fatty acids, osteoprotegerin/the soluble receptor activator of nuclear factor-kappabeta ligand systems, and bone mineral density.

Bone disease in beta-thalassemia major (betaTM) remains poorly understood. Receptor activator of nuclear factor-kappabeta ligand (RANKL) regulates osteoclast formation and function. RANKL activity is balanced by interaction with its receptor (RANK) and binding to osteoprotegerin (OPG). L-Carnitine (LC) enhances osteoblastic activity by furnishing fuel. This study hypothesized that abnormal bone metabolism in betaTM involves imbalanced RANKL/OPG and LC/free fatty acids (FFAs) metabolism. Sixty-nine transfusion-dependent betaTM patients and 15 healthy controls were enrolled. One group of patients (n=34) received desferrioxamine (DFO) and the other (n=35) did not. Serum OPG, soluble RANKL (sRANKL), FFAs, LC [total LC (TC), free LC (FC), and esterified LC (EC)], calcium, and inorganic phosphate were measured by specific immuno and colorimetric assays; bone mineral density was examined by dual x-ray absorptiometry. Patients showed lower levels of OPG, TC, FC, EC and higher levels of sRANKL, sRANKL/OPG ratio, and FFAs than controls. Patients on DFO showed lower levels of OPG, TC, FC and higher levels of sRANKL, sRANKL/OPG ratio, and FFAs than those without chelation. In patients, sRANKL correlated negatively with TC and OPG and FC correlated positively with OPG and negatively with sRANKL, sRANKL/OPG ratio, and FFAs. In conclusion, altered bone metabolism owing to imbalanced osteoclastic bone resorption versus constructive osteoblastic activities in betaTM pediatric patients could be due to abnormal sRANKL-OPG and LC-FFAs systems that were worsened by DFO.

Dyslipidemia, oxidative stress and cardiac dysfunction in children with chronic renal failure: effects of L-carnitine supplementation.

BACKGROUND: Secondary carnitine deficiency may develop in chronic renal failure (CRF) patients undergoing long-term hemodialysis (HD), with a resulting higher incidence of cardiovascular diseases, dyslipidemia and oxidative stress. We studied the efficacy of 12 months of L-carnitine supplementation on the amelioration of dyslipidemia, oxidative stress and cardiac dysfunction in 24 CRF children undergoing long-term HD compared with 24 age- and sex-matched controls. METHODS: Plasma samples were analyzed spectrophotometerically before and after dialysis sessions and after 2-month supplementation with oral L-carnitine (50 mg/kg/day) for free carnitine (FC), the lipid profile, and oxidative stress markers. Echocardiography the day following dialysis measured cardiac diameters, wall thicknesses, left ventricular mass index (MI), end diastole and systole volume indices and functions. RESULTS: The pre-dialysis FC concentration was substantially lower than controls and decreased significantly at the end of the dialysis session. Pre- and post-dialysis plasma levels of free fatty acids (FFAs), trigyleride (TG), total cholesterol (TC) and oxidative stress markers significantly increased while high-density lipoprotein cholesterol (HDL-C) and phospholipids significantly decreased compared to controls. Echocardiography detected a significant increase in cardiac diameters and thickness, and systolic and diastolic cardiac dysfunction. After L-carnitine supplementation, plasma levels of FC increased to normal levels. FFAs, TC and HDL-C returned to control levels while TG, phospholipids, and the oxidative stress markers decreased but remained significantly higher than controls. There was a significant decrease in cardiac diameters and an increase in left ventricular diastolic function (E/A ratio), but no correlation between FC levels and echocardiographic parameters. Pre-dialysis, post-dialysis and after treatment, plasma FC level showed a significant positive correlation with HDL-C and phospholipids and a significant negative correlation with each of oxidative stress markers, FFAs, TG and TC. On the other hand, FFAs showed a significant positive correlation with TG, TC, DC, NO and a significant negative correlation with HDL-C and phospholipids. CONCLUSION: This study demonstrates that CRF children under regular HD suffer from a decrease in the level of plasma FC, dyslipidemia, oxidative stress, and an increase in cardiac diameters and thickness with impairment of cardiac functions. Oral L-carnitine supplementation at a dose of 50 mg/kg for 2 months can increase plasma FC level, improve dyslipidemia, decrease oxidative stress with reduction of cardiac diameters and increase in diastolic function.