ABSTRACT
BACKGROUND: Brain natriuretic peptide and its derivative peptide NTproBNP are utilized to exclude cardiac diseases, and predicting risk of mortality in dialysis patients. Our aim was to evaluate both elimination of NTproBNP through dialysate and a possible relationship between plasma and/or dialysate NTproBNP level and membrane transport status of peritoneal dialysis patients. METHODS: 57 plasma (P) and dialysate (D) samples of 44 peritoneal dialysis (PD) patients were analyzed for NTproBNP. Modified peritoneal equilibration test (PET) results and other variables were obtained from the charts. RESULTS: Median (IQR) NTproBNP concentrations (pg/mL × 1,000) in P and D were 3.3 (1 - 13) and 0.5 (0.2 - 3.6), respectively. There was a linear correlation between P-NTproBNP and D-NTproBNP (r = 0.928, p = 0.0001; regression equation was y = 0.897*x -0.28). Mean P/D-NTproBNP ratio was 5.5 ± 0.5. Median P and D-NTproBNP levels by the membrane transport status were aligned as high (H) > high average (HA) > low average (LA), and the difference between H and LA was statistically significant (p < 0.001). Mean arterial pressure (MAP), residual Kt/V and dialysate/plasma ratio of crearinine (D/P Cr) were significant predictors of D-NTproBNP; whereas only MAP and residual Kt/V were significant predictors of P-NTproBNP in multiple regression analysis. Both P- and D-NTproBNP have significant and similar size of correlations with MAP, albumin, D/P Cr ratio, and Na. CONCLUSIONS: D-NTproBNP level is ~ 1/5 of P-NTproBNP, and the issue of relationship between membrane transport status and natriuretic peptide levels needs more work.
Subject(s)
Dialysis Solutions/chemistry , Kidney Failure, Chronic/therapy , Membranes, Artificial , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Peritoneal Dialysis/instrumentation , Adult , Arterial Pressure , Biological Transport , Creatinine/analysis , Female , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Natriuretic Peptide, Brain/analysis , Peptide Fragments/analysis , Peritoneum/metabolism , Serum Albumin/metabolism , Sodium/bloodABSTRACT
We aimed to study the effects of gingko biloba extract (EGb) on oxidative stress, astrocyte maturation and cognitive disfunction in offspring of hyperhomocysteinemic rats. Hyperhomocysteinemia was induced in the pregnant rats by administration of methionine (1 gr/kg body weight) dissolved in drinking water throughout pregnancy. One group of animals has received same amount of methionine plus 100 mg/kg/day EGb during pregnancy. On the postnatal day 1, half of the pups from all groups were sacrificed to study the lipid peroxidation (LPO) in different subfractions of brain. Other half of pups were tested in Morris water maze to assess differences in learning and memory performance at the 75 days of age. Maternal hyperhomocysteinemia significantly increased LPO levels especially in mitochondrial subfraction of fetal pup brains. EGb significantly prevented this LPO inrease. Methionine administration to animals reduced glial fibrillary acidic protein (GFAP) expression in pup brains significantly. EGb administration improved GFAP expression significantly. Offspring of hyperhomocysteinemic animals had poor long term spatial memory performance on Morris water maze and EGb administration had no effect on impaired spatial memory. In conclusion, maternally induced hyperhomocysteinemia significantly increased oxidative stress, decreased expression of GFAP and impaired learning performance.
Subject(s)
Glial Fibrillary Acidic Protein/metabolism , Hyperhomocysteinemia/physiopathology , Maze Learning/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Animals , Behavior, Animal/drug effects , Brain/drug effects , Brain/metabolism , Female , Ginkgo biloba/chemistry , Lipid Peroxidation , Male , Memory/drug effects , Methionine , Mitochondria/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/physiopathology , Rats , Rats, WistarABSTRACT
Maternal hyperhomocysteinemia is associated with a number of complications such as preeclampsia syndrome, thromboembolic events, repeated miscarriages, abruptio placentae, in utero fetal death, intrauterine fetal growth restriction and fetal neural tube defects. However, little is known about the mechanism of homocysteine on the degeneration of fetal brain. Thus, our study is aimed to investigate the effects of maternal hyperhomocysteinemia on oxidative stress and apoptosis in pup brain. Hyperhomocysteinemia was induced in female rats by way of administrating methionine dissolved in water at a dose of 1g/kg body weight throughout the pregnancy. After delivery, level of lipid peroxidation (LPO; as malondialdehyde+4-hydroxyalkenals) was determined in various fractions of pub brains. Furthermore, DNA fragmentation, levels of Bcl-2 protein and p53 mRNA expression were determined to evaluate apoptosis. Significant elevation was found in the levels of LPO in subcellular fractions of pup brains delivered from hyperhomocysteinemic mothers. DNA fragmentation, a hallmark of apoptosis was observed in the brain of pups of homocysteine group while significant reduction was seen in the levels of anti-apoptotic Bcl-2 levels. In addition, maternal hyperhomocysteinemia increased cerebral p53 mRNA expression above the control value. As a conclusion, we demonstrate and suggest that the pups of hyperhomocysteinemic mothers have an increased oxidative stress in brain tissues. The increased oxidative stress appears to cause apoptosis and cell death. These results may be significant to understand chronic pathology of the complications of hyperhomocysteinemia and congenital malformations of fetuses.
Subject(s)
Apoptosis/physiology , Brain/physiopathology , Hyperhomocysteinemia/chemically induced , Methionine/administration & dosage , Oxidative Stress/physiology , Animals , Animals, Newborn , Blotting, Western , Brain/metabolism , DNA Fragmentation , Female , Hyperhomocysteinemia/metabolism , Hyperhomocysteinemia/physiopathology , Lipid Peroxidation/physiology , Maternal-Fetal Exchange , Pregnancy , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
Chronic hyperhomocysteinemia is a risk factor in cardiovascular diseases and neurodegeneration. Among the putative mechanisms of homocysteine-induced neurotoxicity, an increased production of reactive oxygen species has been suggested. However, elevated homocysteine levels might disturb neurogenesis during brain development and lead to persistent congenital malformations in the fetus. In this study, we examined whether administration of melatonin inhibits maternal hyperhomocysteinemia-induced cognitive deficits in offspring. Hyperhomocysteinemia was induced in female rats by administration of methionine during pregnancy at a dose of 1 g/kg body weight dissolved in drinking water. Some animals received methionine plus 10 mg/kg/day melatonin subcutaneously throughout pregnancy. The levels of glial fibrillary acidic protein, S100B protein, and neural cell adhesion molecules were determined in the brain tissue from the pups. Learning and memory performances of the young-adult offspring were tested using the Morris water maze test. There were significant reductions in the expression of glial fibrillary acidic protein and S100 B protein in the brains of pups from hyperhomocysteinemic rat dams. Furthermore, maternal hyperhomocysteinemia altered the expression pattern of neural cell adhesion molecules in the fetal brain. In addition, maternal hyperhomocysteinemia significantly reduced learning abilities in offspring. Treatment with melatonin during pregnancy improved learning deficits and prevented the reduction of glial and neuronal markers induced by hyperhomocysteinemia. In conclusion, administration of melatonin throughout pregnancy reduces the effects of hyperhomocysteinemia on the development of fetal brain; therefore, it might be beneficial in preventing persistent congenital malformations.
Subject(s)
Behavior, Animal/drug effects , Cognition Disorders/metabolism , Cognition Disorders/prevention & control , Hyperhomocysteinemia/metabolism , Hyperhomocysteinemia/physiopathology , Melatonin/physiology , Animals , Animals, Newborn , Behavior, Animal/physiology , Cognition Disorders/physiopathology , Female , Hyperhomocysteinemia/complications , Male , Melatonin/administration & dosage , Pregnancy , Random Allocation , Rats , Rats, WistarABSTRACT
Moderate hyperhomocysteinemia is a risk factor for neurodegenerative diseases and complications during pregnancy. Increased homocysteine levels during pregnancy may elevate developmental risk on fetal brain structure and function. However, little is known about the mechanism of action of homocysteine on the degeneration of the fetal brain. Hence in this study, we examined the effects of maternal hyperhomocysteinemia on oxidative stress and apoptosis in brain tissues and investigated whether administration of melatonin to the mother would prevent homocysteine-induced oxidative cerebral damage in pups. Hyperhomocysteinemia was induced in female rats by administration of methionine at a dose of 1 g/kg body weight dissolved in drinking water during pregnancy. Some animals received methionine plus 10 mg/kg/day melatonin subcutaneously throughout pregnancy. After delivery, the level of lipid peroxidation (malondialdehyde + 4-hydroxyalkenals) was determined in different subfractions of pup brains. Furthermore, DNA fragmentation, levels of Bcl-2 protein and p53 mRNA expression were determined to evaluate apoptosis. Significant elevation was found in the levels of lipid peroxidation in subcellular fractions of the brain of pups of hyperhomocysteinemic dams. Increased DNA fragmentation and p53 mRNA expression was observed in the brain of pups of homocysteine-treated rats, while a significant reduction was seen in the levels of anti-apoptotic Bcl-2 levels. Melatonin administration prevented markers of oxidative stress and biochemical signs of apoptosis. In conclusion, therapeutic administration of melatonin protects against the induction of oxidative stress and neural tissue injury and might prevent congenital malformations of fetal brain caused by maternal hyperhomocysteinemia.
Subject(s)
Apoptosis/drug effects , Brain/drug effects , Brain/metabolism , Hyperhomocysteinemia/metabolism , Hyperhomocysteinemia/pathology , Melatonin/pharmacology , Oxidative Stress/drug effects , Animals , Brain/cytology , Brain/embryology , Cell Nucleus/metabolism , Female , Glutathione/metabolism , Hyperhomocysteinemia/drug therapy , Hyperhomocysteinemia/genetics , Lipid Peroxidation , Mitochondria/metabolism , Organ Size/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/genetics , Rats , Rats, Wistar , Tumor Suppressor Protein p53/geneticsABSTRACT
In this study, we suggest that chronic maternal hyperhomocysteinemia results in learning deficits in the offspring due to delayed brain maturation and altered expression pattern of neural cell adhesion molecule. Although the deleterious effects of hyperhomocysteinemia were extensively investigated in the adults, there is no clear evidence suggesting its action on the developing fetal rat brain and cognitive functions of the offspring. Therefore, in the present work we aimed to investigate effects of maternal hyperhomocysteinemia on the fetal brain development and on the behavior of the offspring. A group of pregnant rats received daily methionine (1 g/kg body weight) dissolved in drinking water to induce maternal hyperhomocysteinemia, starting in the beginning of gestational day 0. The levels of glial fibrillary acidic protein, S100B protein, and neural cell adhesion molecule were determined in the tissue samples from the pups. Learning and memory performances of the young-adult offsprings were tested using Morris water maze test. There were significant reductions in the expressions of glial fibrillary acidic protein and S100B protein in the brains of maternally hyperhomocysteinemic pups on postnatal day 1, suggesting that hyperhomocysteinemia delays brain maturation. In conclusion, maternal hyperhomocysteinemia changes the expression pattern of neural cell adhesion molecule and therefore leads to an impairment in the learning performance of the offspring.
Subject(s)
Hyperhomocysteinemia/chemically induced , Hyperhomocysteinemia/complications , Maze Learning/physiology , Memory/physiology , Methionine , Prenatal Exposure Delayed Effects , Animals , Animals, Newborn , Brain/metabolism , Brain/pathology , Female , Gene Expression Regulation, Developmental/physiology , Glial Fibrillary Acidic Protein/metabolism , Hyperhomocysteinemia/metabolism , Hyperhomocysteinemia/pathology , Male , Nerve Growth Factors/metabolism , Neural Cell Adhesion Molecule L1/metabolism , Pregnancy , Rats , Rats, Wistar , S100 Calcium Binding Protein beta Subunit , S100 Proteins/metabolism , Sialic Acids/metabolismABSTRACT
Oxidative stress has been proposed as a possible mechanism underlying many neurodegenerative diseases associated with hyperhomocysteinemia. In the present study, we investigated the possible link between oxidative stress, expression of neural cell adhesion molecules and spatial learning deficits induced by chronic hyperhomocysteinemia. Furthermore, the effectiveness of antioxidant melatonin against homocysteine neurotoxicity was also examined. Male Wistar rats were treated with either saline or methionine to induce hyperhomocysteinemia and half of methionine-treated rats administered daily melatonin in a dose of 10 mg/kg. We observed that chronic administration of melatonin significantly reduced the lipid peroxidation and restored the decreased glutathione levels induced by chronic hyperhomocysteinemia. Chronic hyperhomocysteinemia significantly impaired learning and memory performance in the passive avoidance test and Morris water maze task. We also found that these cognitive deficits were reversed by chronic treatment with antioxidant melatonin. Furthermore, melatonin administration was able to modulate the expression pattern of neural cell adhesion molecules in hippocampus. The results provide evidence that homocysteine induces long-lasting behavioral deficits, which are possibly caused by oxygen reactive species generation, and by changing in synaptic plasticity and also suggest that melatonin treatment has the ability to prevent nervous system against homocysteine toxicity.