Melatonin and vitamin E alleviate homocysteine-induced oxidative injury and apoptosis in endothelial cells.

A relationship exists between hyperhomocysteinemia and cardiovascular diseases, although the underlying mechanisms are still incompletely defined. One possibility involves a homocysteine (Hcy)-induced increased oxidative stress. Melatonin (Mel) and vitamin E (vitE) are important anti-oxidants. The main purpose of this study was (1) to compare the effect of treatments with Mel, vitE or both, on Hcy-induced apoptosis in human umbilical vein endothelial cells (HUVECs), and (2) to investigate the underlying mechanisms. Cell proliferation assay was carried out by Water Soluble Tetrazolium-1 (WST-1) assay kit. Apoptotic index was calculated by TUNEL Assay. Anti-oxidant parameters were studied by measurement of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. mRNA and protein expression levels of apoptotic and anti-apoptotic genes and proteins were studied by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting experiments respectively. The results showed that treatments with Mel, vitE or Mel + vitE suppressed Hcy-induced cell death, with a higher efficiency for the Mel and Mel + vitE treatments. Our results suggests that the mechanisms by which these anti-oxidants protected endothelial cells include the decrease in ROS and LPO levels, an increase in cell migration, the downregulation of pro-apoptotic proteins Cas 3, Cas 9, Cyt C and Bax and the upregulation of anti-apoptotic protein Bcl 2. Collectively, these results revealed the protective role of vitE and Mel against Hcy-induced cell apoptosis, which may add insight into therapeutic approaches to Hcy-induced damages.

The effects of hydrated C(60) fullerene on gene expression profile of TRPM2 and TRPM7 in hyperhomocysteinemic mice.

BACKGROUND: Hyperhomocysteinemia (HHcy) is associated with neurodegenerative diseases. Transient receptor potential melastatin (TRPM2) and TRPM7 channels may be activated by oxidative stress. Hydrated C(60) fullerene (C(60)HyFn) have recently gained considerable attention as promising candidates for neurodegenerative states. We aimed to examine the effects on TRPM2 and TRPM7 gene expression of C(60)HyFn due to marked antioxidant activity in HHcy mice. METHODS: C57BL/6 J. mice were divided into four groups: (1) Control group, (2) HHcy, (3) HHcy + C(60)HyFn-treated group and (4) C(60)HyFn-treated group. TRPM2 and TRPM7 gene expression in brains of mice were detected by real-time PCR, Western blotting and immunohistochemistry. Apoptosis in brain were assessed by TUNEL staining. RESULTS: mRNA expression levels of TRPM2 were significantly increased in HHcy group compared to the control group. C(60)HyFn administration significantly decreased serum levels of homocysteine and TRPM2 mRNA levels in HHcy + C(60)HyFn group. Whereas, HHcy-treatment and C(60)HyFn administration did not change the expression of TRPM7. CONCLUSION: Administration of C(60)HyFn in HHcy mice significantly reduces serum homocysteine level, neuronal apoptosis and expression level of TRPM2 gene. Increased expression level of TRPM2 induced by oxidative stress might be involved in the ethiopathogenesis of HHcy related neurologic diseases.

Effects of the neonicotinoid insecticide, clothianidin, on the reproductive organ system in adult male rats.

Clothianidin (CTD) is a novel, broad-spectrum insecticide. In the current study, it was aimed to study the effect of subchronic exposure to low doses of CTD (2, 8 and 24 mg/kg body weight/day) on the reproductive system in adult rats. CTD treatment did not significantly change serum testosterone level or sperm parameters (e.g. concentration, motility and morphology), but caused significant decreases in weights of epididymis, right cauda epididymis and seminal vesicles. CTD treatment did not cause sperm DNA fragmentation and did not change the apoptotic index in the seminiferous tubules and levels of α-tocopherol and glutathione, but increased the level of thiobarbituric acid-reactive substances and cholesterol levels significantly at all doses. CTD exposure caused significant elevations in palmitic, linoleic and arachidonic acids in testis in all CTD-exposed groups. There was a drop in 20:4/18:2 (arachidonic acid/linoleic acid) ratio and an increase in 18:1n-9/18:0 (oleic acid/stearic acid) ratios in all CTD groups, in comparison to the control group. In conclusion, CTD had little detectable detrimental effects on the reproductive system of male rats over the measured parameters.

Effects of clothianidin exposure on sperm quality, testicular apoptosis and fatty acid composition in developing male rats.

Clothianidin (CTD) is one of the latest members of the synthetic organic insecticides, the neonicotinoids. In the present study, it was aimed to investigate if daily oral administration of CTD at low doses for 90 days has any deleterious effects on reproductive functions of developing male rats. Animals were randomly divided into four groups of six rats each, assigned as control rats, or rats treated with 2 (CTD-2), 8 (CTD-8) or 32 (CTD-32) mg CTD/kg body weight by oral gavage. The significant decreases of the absolute weights of right cauda epididymis and seminal vesicles, and body weight were detected in the animals exposed to CTD administration at 32 mg/kgBW/day. Epididymal sperm concentration decreased significantly in CTD-32 group and the abnormal sperm rates increased in CTD-8 and CTD-32 groups when compared to control group. The testosterone level was significantly decreased in CTD-32 group when compared to control group. The administration of all CTD doses resulted in a significant decrease in the level of GSH. The number of TUNEL-positive cells significantly increased in the germinal epithelium of testis of rats exposed to CTD at 32 mg/kgBW/day. In groups CTD-8 and CTD-32, only docosapentaenoic, arachidonic, palmitic and palmitoleic acids were significantly elevated when compared to control. The ratios of 20:4/18:2 and 18:1n-9/18:0 were decreased when rats exposed to CTD. Sperm DNA fragmentation was observed in CTD-32 group, but not CTD-2 and CTD-8. It is concluded that low doses of CTD exposure during critical stages of sexual maturation had moderate detrimental effects on reproductive organ system and more severe effects are likely to be observed at higher dose levels. In addition, the reproductive system may be more sensitive to exposure of CTD even earlier in development (prenatal and early postnatal), and therefore it could be expected that more severe effects could also be observed at the NOAEL dose levels, if dosing had occurred in utero or early postnatal.

Insecticide imidacloprid induces morphological and DNA damage through oxidative toxicity on the reproductive organs of developing male rats.

We investigated whether treatment with imidacloprid would induce morphological changes, DNA fragmentation, antioxidant imbalance and apoptosis in the reproductive system of developing male rats. Twenty-four male rats were included in this 90-day study, starting at 7 days of age. The rats were divided into four groups. The first group was used as control. The second, third and fourth groups received oral 0.5-, 2- and 8-mg/kg imidacloprid, respectively. Serum, sperm and testis samples were collected from all groups at the end of the experimental period. The weights of the epididymis, vesicula seminalis, epididymal sperm concentration, body weight gain, testosterone and reduced glutathione values were lower in the imidacloprid-treated groups than that in the controls. All treated groups had increased lipid peroxidation, fatty acid concentrations and higher rates of abnormal sperm. Apoptosis and fragmentation of seminal DNA were higher in rats treated at the two higher doses of imidacloprid. These results show that this compound has a negative effect on sperm and testis of rats.

Gingko biloba extract inhibits oxidative stress and ameliorates impaired glial fibrillary acidic protein expression, but can not improve spatial learning in offspring from hyperhomocysteinemic rat dams.

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.

Melatonin prevents gestational hyperhomocysteinemia-associated alterations in neurobehavioral developments in rats.

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.

Effects of maternal hyperhomocysteinemia induced by high methionine diet on the learning and memory performance in offspring.

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.

Effect of melatonin and vitamin E on diabetes-induced learning and memory impairment in rats.

Previous studies indicate that diabetes mellitus might be accompanied by a certain erosion of brain function such as cognitive impairment. The aim of this study was to examine and compare the effects of melatonin and vitamin E on cognitive functions in diabetic rats. Diabetes was induced in male albino rats via intraperitoneal streptozotocin injection. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. The levels of lipid peroxidation and glutathione were detected in hippocampus and frontal cortex. The diabetic rats developed significant impairment in learning and memory behaviors as indicated by the deficits in water maze tests as compared to control rats. Furthermore, lipid peroxidation levels increased and glutathione concentration decreased in diabetic rats. Treatment with melatonin and vitamin E significantly ameliorated learning and memory performance. Furthermore, both antioxidants reversed lipid peroxidation and glutathione levels toward their control values. These results suggest that oxidative stress may contribute to learning and memory deficits in diabetes and further suggest that antioxidant melatonin and vitamin E can improve cognitive impairment in streptozotocin-induced diabetes.

Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis.

Chronic cardiovascular and neurodegenerative complications induced by hyperhomocysteinemia have been most relatively associated with endothelial cell injury. Elevated homocysteine (Hcy) generates reactive oxygen species (ROS) accompanying with oxidative stress which is hallmarks of the molecular mechanisms responsible for cardiovascular disease. Propolis is a natural product, obtained by honeybee from various oils, pollens, special resins and wax materials, conventionally used with the purpose of treatment by folks Propolis has various biological activities and powerful antioxidant capacity. The flavonoids and phenolic acids, most bioactive components of propolis, have superior antioxidant ability to defend cell from free radicals. This study was designed to examine the protective effects of Turkish propolis (from east of country) on Hcy induced ROS production and apoptosis in human vascular endothelial cells (HUVECs). According to results, co-treatment of HUVECs with propolis decreased Hcy-induced ROS overproduction and lipid peroxidation (LPO) levels. Furthermore, overproductions of Bax, caspase-9 and caspase-3 protein, elevation of cytochrome c release in Hcy-treated HUVECs were significantly reduced by propolis. It was concluded that propolis has cytoprotective ability against cytotoxic effects of high Hcy in HUVECs.

Turkish propolis supresses MCF-7 cell death induced by homocysteine.

Elevated plasma homocysteine (Hcy) level is a most important risk factor for various vascular diseases including coronary, cerebral and peripheral arterial and venous thrombosis. Propolis is produced by honeybee from various oils, pollens and wax materials. Therefore, it has various biological properties including antioxidant, antitumor and antimicrobial activities. This study investigated the effects of propolis and Hcy on apoptosis in cancer cells. According to our findings, Hcy induced apoptosis in human breast adenocarcinoma (MCF-7) cells by regulating numerous genes and proteins involved in the apoptotic signal transduction pathway. In contrast, treatment with propolis inhibited caspase- 3 and -9 induced by Hcy in MCF-7 cells. It can be concluded that Hcy may augment the activity of anticancer agents that induce excessive reactive oxygen species (ROS) generation and apoptosis in their target cells. In contrast to the previous studies herein we found that propolis in low doses protected cancer cells inhibiting cellular apoptosis mediated by intracellular ROS-dependent mitochondrial pathway.

Melatonin improves learning and memory performances impaired by hyperhomocysteinemia in rats.

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.

Effects of thinner exposure on the expression pattern of neural cell adhesion molecules, level of lipid peroxidation in the brain and cognitive function in rats.

Thinner containing 60-70% toluene is a neurotoxic mixture, which is widely used as an aromatic industrial solvent. This product has been shown to cause functional and structural changes in the central nervous system. Thinner generates reactive oxygen species and the toxic effects relating to these reactants. We have investigated the effect of exposure to high concentrations (3000 ppm) of thinner for 45 days (1 h/day) on cognitive function and the levels of neural cell adhesion molecules (NCAM) and lipid peroxidation products in the hippocampus, cortex and cerebellum of rats. Thinner exposure caused a significant increase in lipid peroxidation products (malondialdehyde and 4-hydroxyalkenals) in all brain regions. Levels of NCAM 140 and NCAM 180 kDa were significantly decreased in the hippocampus and cortex of the thinner-exposed group. Furthermore, thinner-exposed rats showed cognitive deficits in passive avoidance and Morris water maze tasks. These cognitive deficits may be due to both elevated oxidative stress and changes in synaptic plasticity. Almost all studied parameters were reversed in animals which were allowed to recover from thinner inhalation, suggesting that the effects of exposure to thinner, at least for 1 h/day for 45 days, are reversible.

Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats.

Hyperglycemia plays a critical role in the development and progression of diabetic neuropathy. One of the mechanisms by which hyperglycemia causes neural degeneration is via the increased oxidative stress that accompanies diabetes. Metabolic and oxidative insults often cause rapid changes in glial cells. Key indicators of this response are increased synthesis of glial fibrillary acidic protein (GFAP) and S100B, both astrocytic markers. In the present study, we examined glial reactivity in hippocampus, cortex, and cerebellum of streptozotocin (STZ)-induced diabetic rats by determining the expression of GFAP and S-100B and we evaluated the effect of melatonin on the glial response. Western blot measurement of contents in brain regions after 6 weeks of STZ-induced diabetes indicated significant increases in these constituents compared with those in nondiabetic controls. Administration of melatonin prevented the upregulation of GFAP in all brain regions of diabetic rats. Using GFAP immunohistochemistry, we observed an increase in GFAP immunostaining in the hippocampus of STZ-diabetic rats relative to levels in the control brains. Treatment with melatonin resulted in an obvious reduction of GFAP-immunoreactive astrocytes in hippocampus. Like GFAP, S100B levels also were increased in all three brain areas of diabetic rats, an effect also reduced by melatonin treatment. Finally, the levels of lipid peroxidation products were elevated as a consequence of diabetes, with this change also being prevented by melatonin. These results suggest that diabetes causes increased glial reactivity possibly due to elevated oxidative stress, and administration of melatonin represents an achievable adjunct therapy for preventing gliosis.

Increase of glial fibrillary acidic protein and S-100B in hippocampus and cortex of diabetic rats: effects of vitamin E.

Glial interactions with neurones play vital roles during the ontogeny of the nervous system and in the adult brain. Physical and metabolic insults cause rapid changes in the glial cells and this phenomenon is called reactive gliosis. One of the important events during astrocyte differentiation is the increased expression of glial markers, glial fibrillary acidic protein (GFAP) and S-100B protein. Diabetes mellitus is the most common serious metabolic disorder, which is characterised by functional and structural changes in the peripheral as well as in the central nervous system. In the present study, we aimed to investigate glial reactivity in hippocampus, cortex and cerebellum of streptozotocin-induced diabetic rats by determining the expression of GFAP and S-100B and also to examine the protective effects of vitamin E against gliosis. Western blotting showed increases in total and degraded GFAP content and S-100B protein expression in brain tissues of diabetic rats compared with those of controls. In addition, there was a significant increase in lipid peroxidation in these brain regions of diabetic rats. Both glial markers and lipid peroxidation levels were reversed by vitamin E administration. These findings indicate that streptozotocin-induced diabetes alters degradation and production of GFAP and S-100B, which are markers of reactive astrocytosis. Thus, determination of GFAP and S-100B may provide a relevant marker in the central nervous system for studying neurodegenerative changes in experimental diabetes mellitus. This study also suggests that the gliosis that occurs in diabetes mellitus is mediated, at least indirectly, by free radical formation and antioxidants may prevent reactive gliosis possibly by reducing damaging effects of reactive oxygen species in the central nervous system.

Daily rhythm of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats.

Melatonin is a component of the antioxidant defense system since it has radical scavenging and antioxidant activities. In the present study, we aimed to investigate the endogenous rhythm of antioxidant enzyme glutathione peroxidase (GSH-Px) activity, oxidized glutathione (GSSG) and lipid peroxidation levels in tissues of pinealectomized rats (PINX). Rats were sacrificed by decapitation at 4 h intervals. GSH-Px activity, GSSG and lipid peroxidation levels showed a daily rhythm both in controls and in PINX rats. GSH-Px and GSSG exhibited the peak levels after the peak time of melatonin which was determined previously by other groups. Lipid peroxidation levels increased progressively during the night and started to decline before the GSH-Px peak time. These findings suggest that endogenous melatonin is involved in the night time increase of GSH-Px activity and GSSG levels and modulates the daily rhythm pattern of GSH-Px. In conclusion, pinealectomy which eliminates the melatonin rhythm has a supressor effect on GSH-Px activity levels.

Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin-induced diabetes mellitus.

Neurological and structural changes are paralleled by cognitive deficits in diabetes mellitus. The present study was designed to evaluate the expression of neural cell adhesion molecules (NCAM) in the hippocampus, cortex and cerebellum and to examine cognitive functions in diabetic rats. Diabetes was induced in male albino rats via intraperitoneal streptozotocin injection. Learning and memory behaviors were investigated using a passive avoidance test and a spatial version of the Morris water maze test. NCAM expression was detected in the hippocampus, cortex and cerebellum by an immunoblotting method. The diabetic rats developed significant impairment in learning and memory behaviours as indicated by deficits in passive avoidance and water maze tests as compared to control rats. Expression of NCAM 180 and 120 kDa were found to be higher in hippocampus and cortex of diabetic rat brains compared to those of control, whereas expression of NCAM 140 kDa decreased in these brain regions. Our findings suggest that streptozotocin-induced diabetes impairs cognitive functions and causes an imbalance in expression of NCAM in those brain regions involved in learning and memory. Altered expression of NCAM in hippocampus may be an important cause of learning and memory deficits that occur in diabetes mellitus.

Effects of certain micronutrients and melatonin on plasma lipid, lipid peroxidation, and homocysteine levels in rats.

BACKGROUND: Numerous studies suggest an association between high intake of antioxidant vitamins and fish oil and reduced risk of coronary heart disease. Hyperhomocysteinemia has also been identified as an independent risk factor for arteriosclerosis. In this paper, we aimed to evaluate the effects of vitamin E, vitamin C, vitamin C 6 palmitate (VC6P), lipoic acid, fish oil, and melatonin supplementation on lipid peroxidation, plasma lipid, and homocysteine (Hcy) levels in rats. METHODS: Animals were divided into seven groups: one was used as control and each remaining group was supplemented with one substance for 6 weeks. All substances were dissolved in olive oil and injected intraperitoneally (i.p.) with the exception of vitamin C, which was dissolved in drinking water. Plasma Hcy, lipid peroxidation, and lipids were determined. RESULTS: Plasma malondialdehyde (MDA) levels decreased significantly in melatonin (p <0.01), lipoic acid (p <0.01), and vitamin E (p <0.05) groups. On the other hand, supplementation with vitamin C and VC6OP lowered MDA levels moderately but not significantly (p >0.05). Fish oil supplementation caused a slight but insignificant increase in plasma MDA levels (p >0.05). Plasma lipid levels in animals treated with melatonin, vitamin E, vitamin C, lipoic acid, and fish oil were significantly lower than those of controls; however, treatment of rats with VC6P has no significant effect on plasma lipid level. Melatonin and fish oil administration significantly lowered plasma Hcy levels, whereas VC6P elevated its level. There was no significant effect of vitamin E, vitamin C, and lipoic acid on levels of plasma Hcy. CONCLUSIONS: Our data suggest that supplementation with antioxidants appears to be hypolipidemic. In addition to these beneficial effects, administration of melatonin and fish oil deserves careful consideration as a measure to lower plasma Hcy levels and reduce risk of cardiovascular diseases.

Insulin increases homocysteine levels in a dose-dependent manner in diabetic rats.

BACKGROUND: Even moderate increases in levels of homocysteine cause cardiovascular degeneration. Various genetic and nutritional factors affect plasma homocysteine concentrations, and hyperhomocysteinemia damages vascular endothelial cells; hence their functions are disrupted. In diabetes mellitus, homocysteine metabolism is altered and as a result, more severe diabetic complications are expected when hyperhomocysteinemia occurs. METHODS: In the present study we experimentally induced diabetes in rats and examined effects of low or high dose of insulin administration on homocysteine metabolism. RESULTS: We determined that homocysteine levels were reduced in STZ-induced diabetic rats. This reduction was normalized by insulin in a dose-dependent manner. On the other hand, increased levels of lipid parameters (cholesterol, triglycerides, HDL) were reduced by insulin. CONCLUSIONS: Hcy level in experimentally induced insulin-dependent diabetes mellitus is decreased and injection of insulin normalizes Hcy levels in a dose-dependent manner. We speculate that insulin increases activities of enzymes of transsulfuration and remethylation reactions and hence speeds up conversion of Hcy to methionine and cysteine.

Antioxidant vitamin levels in term and preterm infants and their relation to maternal vitamin status.

BACKGROUND: Lipid peroxidation plays a vital role in the pathogenesis of many neonatal complications. Preterm babies are especially predisposed to lung diseases and retinopathy, probably due to a deficiency in their antioxidant systems. Vitamins E, A, and C are part of the natural antioxidant defense systems. We aimed to determine the levels of vitamins E, A, and C in maternal and cord blood plasma of term and preterm infants and to investigate the relationships between these levels. METHODS: In the present study we determined vitamin E, A, and C levels in the umbilical cord blood of term (n = 30) and preterm (n = 22) infants and their mothers by HPLC. Blood samples were taken during delivery. RESULTS: Levels of lipid soluble antioxidant vitamin E and A in cord blood were lower than maternal values (p <0.01, p <0.05, respectively). Conversely, the level of water-soluble vitamin C was higher in cord blood than in maternal level (p <0.05). Significantly higher levels of vitamins E, A, and C were found in term babies as compared with those born preterm (p <0.05). CONCLUSIONS: There was a positive correlation between maternal and cord blood levels of vitamins E and A (r = 0.775, r = 0.725, respectively). In conclusion, preterm babies have fewer lipid-soluble antioxidant vitamins in their serum compared to term infants. Therefore, it is possible to postulate that preterm infants are more susceptible to oxidative stress.