Protective effects of copper against aluminum toxicity on acetylcholinesterase and catecholamine contents of different regions of rat's brain.

The probable protective effects of copper on the acetylcholinesterase activity and the catecholamine levels in cerebellum, cortex and mid-brain of rat, which was intoxicated by aluminum, were studied during short and long terms. In this respect, male Wistar rats weighing 200-250 g were received daily intraperitoneal doses of aluminum, copper and also combined doses of both metals for 15 days (Al 10 mg kg(-1) BW and Cu 1 mg kg(-1) BW), 30 days (Al 5 mg kg(-1) BW and Cu 0.5 mg kg(-1) BW) and 60 days (Al 1 mg kg(-1) BW and Cu 0.1 mg kg(-1) BW), respectively. The results obtained from the short period of exposure (15 days) showed that aluminum produced significant (P < 0.05) decreases in the acetylcholinesterase activity by 24.14, 23.30 and 25.81 %. Similarly, the catecholamine levels were reduced by 10.69, 12.25 and 12.64 % in cerebellum, cortex and mid-brain, respectively. Treatment with copper increases both acetylcholinesterase activity and catecholamine contents of cerebellum, cortex and mid-brain. Simultaneous injection of copper and aluminum increased both acetylcholinesterase activity and catecholamine contents in all three parts of rat brain when compared to aluminum-treated group. Same results were also observed following 30 and 60 days of exposures. In overall, it has been found that copper may have a protective-like ability to hinder aluminum toxicity in the brain.

Distribution of Plasma One-Carbon Metabolism Factors and Amino Acids Profile in Depression State Treated with Paroxetine: A Model Study.

OBJECTIVE: Stress may have an important role in the origin and progress of depression and can impair metabolic homeostasis. The one-carbon cycle (1-CC) metabolism and amino acid (AA) profile are some of the consequences related to stress. In this study, we investigated the Paroxetine treatment effect on the plasma metabolite alterations induced by forced swim stress-induced depression in mice. MATERIALS AND METHODS: In this experimental study that was carried out in 2021, thirty male NMRI mice (6-8 weeks age, 30 ± 5 g) were divided into five groups: control, sham, paroxetine treatment only (7 mg/kg BW/day), depression induction, and Paroxetine+depression. Mice were subjected to a forced swim test (FST) to induce depression and then were treated with Paroxetine, for 35 consecutive days. The swimming and immobility times were recorded during the interventions. Then, animals were sacrificed, plasma was prepared and the concentration of 1-CC factors and twenty AAs was measured by spectrophotometry and high-performance liquid chromatography system (HPLC) techniques. Data were analyzed by SPSS, using One-Way ANOVA and Pearson Correlation, and P<0.05 was considered significant. RESULTS: Plasma concentrations of phenylalanine, glutamate, aspartate, arginine, ornithine, citrulline, threonine, histidine, and alanine were significantly reduced in the depression group in comparison with the control group. The Homocysteine (Hcy) plasma level was increased in the Paroxetine group which can be associated with hyperhomocysteinemia. Moreover, vitamin B12, phenylalanine, glutamate, ornithine, citrulline, and glycine plasma levels were significantly reduced in the depression group after Paroxetine treatment. CONCLUSION: This study has demonstrated an impairment in the plasma metabolites' homeostasis in depression and normal conditions after Paroxetine treatment, although, further studies are required.

Associations between high density lipoprotein mean particle size and serum paraoxonase-1 activity.

BACKGROUND: High density lipoprotein (HDL) particles are heterogeneous in composition, structure, size, and may differ in conferring protection against cardiovascular disease. HDL associated enzyme, paraoxonase-1 (PON1), has an important role in attenuation of atherogenic low density lipoprotein (LDL) oxidation. The aim of this study was to investigate the associations between HDL particle size and PON1 activity in relation to serum HDL cholesterol (HDL-C) levels. MATERIALS AND METHODS: One hundred and forty healthy subjects contributed to this study. HDL was separated by sequential ultracentrifugation and its size was estimated by dynamic light scattering. Paraoxonase activity was measured spectrophotometrically using paraoxon as substrate. RESULTS: Results of this study showed that PON1 activity had negative correlations with HDL mean particle size (r = -0.22, P < 01), HDL2/HDL3 ratio, and serum HDL-C levels (r = -0.25, P < 0.01). HDL mean particle size and HDL2/HDL3 ratio had negative correlation with body mass index (BMI), waist hip ratio (WHR), and serum triglyceride (TG) levels, and positive correlation with serum HDL-C levels. Serum HDL-C levels had significant positive correlations with age, total cholesterol (TC), and apolipoprotein A-I (apo A-I) and significant negative correlation with BMI, WHR, and TG. CONCLUSION: Based on the results of this study, determination of HDL mean particle size beside the serum PON1 activity may help to better understand the CAD risks, pathogenesis, and prognosis, and may also help to design therapeutic protocols toward beneficial modifications of HDL characteristics.

Increased leukocyte ABCA1 gene expression in post-menopausal women on hormone replacement therapy.

OBJECTIVE: The ATP binding cassette A1 (ABCA1) is a key participant in the reverse cholesterol process whereby mediates cholesterol efflux directly to HDL particles. The aim of this study was to investigate whether long-term treatment with conventional hormone replacement therapy (HRT) in post-menopausal women could affect their leukocytes ABCA1 expression. Changes in various serum lipids and lipoprotein fractions were also investigated. MATERIAL AND METHODS: A total of 60 non-obese normolipidaemic post-menopausal women treated with oral oestrogen together with progestin therapy for 3 months were selected. Leukocytes ABCA1 gene expression and serum lipid and lipoprotein concentrations were measured at the start and end of the HRT. RESULTS: HRT led to significant increases in HDL cholesterol (P = 0.001) and apoA-I (P = 0.046) and significant decrease in apoB (P = 0.049) and LDL cholesterol (P = 0.022) when compared with the baseline levels. Analysis of leukocytes ABCA1 mRNA showed a significant increase in ABCA1 gene expression after HRT (P = 0.001). There was also a significant inverse association (r =  -0.28, P = 0.03) between ABCA1 gene expression and log TG/HDL cholesterol changes related to HRT. CONCLUSION: The beneficial cardiovascular effects of HRT could be explained, at least in part, by increasing the ABCA1 gene expression.

Effect of hormone replacement therapy on total serum anti-oxidant potential and oxidized LDL/ß2-glycoprotein I complexes in postmenopausal women.

Oxidative stress and consequent oxidized lipoprotein production is thought to play a central role in both the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (oxLDL)/ß2-glycoprotein I (ß2GPI) complexes are etiologically important in the development of atherosclerosis. The aim of the present study was to investigate whether long-term treatment with conventional hormone replacement therapy (HRT) in postmenopausal women could affect total serum antioxidant capacity (TAC) and serum levels of oxLDL/ß2GPI complexes. A total of 60 normolipidemic postmenopausal women treated with oral estrogen together with progestin therapy for 3 months were selected. TAC and serum levels of oxLDL/ß2GPI complexes were measured at the beginning and end of the HRT. HRT led to a significant increase in TAC (15%, P=0.02) and a minor but statistically nonsignificant decrease of oxLDL/ß2GPI complexes (3%, P=0.30) when compared with the baseline control levels. There was also no significant association between TAC and oxLDL/ß2GPI complexes changes related to HRT. This study indicates that, HRT in postmenopausal women leads to an increase in TAC without an equivalent change in serum levels of oxLDL/ß2GPI complexes. It is concluded that beneficial effects of HRT could be explained, at least in part, by improving antioxidant status, but may not be directly associated with a change in oxidized lipoprotein production.

Comparative effects of copper, iron, vanadium and titanium on low density lipoprotein oxidation in vitro.

INTRODUCTION: Oxidation of low density lipoprotein (LDL) has been strongly implicated in the phathogenesis of atherosclerosis. The use of oxidants in dietary food stuff may lead to the production of oxidized LDL and may increase both the development and the progression of atherosclerosis. The present work investigated the effects of some elements including: copper (Cu), iron (Fe), vanadium (V) and titanium (Ti) on in vitro LDL oxidation quantitatively. METHODS: The first LDL fraction was isolated from fresh plasma by single vertical discontinuous density gradient ultracentrifugation. The formation of conjugated dienes and thiobarbituric acid reactive substances and increase in electrophoretic mobility of LDL were monitored as markers of the oxidation of LDL. RESULTS: It was demonstrated that Cu, Fe, V and Ti exhibited strong oxidant activity in this respect (P<0.001). Oxidation of LDL in the presence of Cu was more and appeared to be in this order Cu>Fe>V>Ti. DISCUSSION: Cu, Fe, V and Ti are redox-active transition metals that may cause oxidative damage to lipids, proteins and DNA molecules. We suggest that these elements may also influence the oxidation of LDL in vivo, which could increase both the development and progression of atherosclerosis.

Long term effects of oral vitamin E supplement in type II diabetic patients.

This triple-blind, placebo-controlled clinical trial was conducted to determine the effect of the vitamin E on fasting blood sugar (FBS), serum insulin, and glycated hemoglobin (GHb) in type 11 diabetic patients (NIDDM). A total of 100 patients, with no complications, aged 20-60 years old were chosen from those consulting the Isfahan Social Security Service Diabetes Clinic and divided randomly into two treated and placebo groups, and matched for age, sex, level of education, and occupation. The treated and placebo groups were given vitamin E tablets (200 IU/day) and placebo respectively. Serum vitamin E, total cholesterol (TC), triglycerides (TG), FBS, insulin, and GHb were measured at the beginning and at the end of the study (a period of 27 weeks); FBS, GHb and insulin levels were also determined several times during the period. Blood lipids and FBS were measured using the ELAN 2000 autoanalyzer at the Isfahan Cardiovascular Research Center, while for measuring insulin the enzyme-linked immunosorbent assay (ELISA) method was used; GHb was determined calorimetrically (thiobarbituric acid), and for vitamin E measurements the Hansen and Warwick method was used, by which the vitamin E was determined fluorometrically. The findings of this study show no effect of vitamin E supplementation in the patients: GHb did not change appreciably, FBS was reduced nonsignificantly (-4.3% in the treated group vs. -14.0% in the placebo group, p < 0.05). In the case of insulin, no increase was seen; instead, a decrease was observed (slightly more than 17% in the two groups, p = 0.15). No changes were observed in the levels of blood lipids. It was concluded that a daily vitamin E supplement of 200 IU for a period of 27 weeks does not affect insulin, GHb, or FBS in type II diabetic patients. However, since this antioxidant vitamin is beneficial in other ways in these patients, it would seem justified to recommend its use. Certainly, more extensive research is necessary to draw definite conclusions.

Vanadyl sulfate ameliorates insulin resistance and restores plasma dehydroepiandrosterone-sulfate levels in fructose-fed, insulin-resistant rats.

OBJECTIVES: To elucidate whether vanadyl sulfate ameliorates the decreased dehydroepiandrosterone sulfate (DHEAS) in hyperinsulinemic rats, we evaluated plasma DHEAS, insulin and triglyceride (TG) levels in fructose-induced, insulin-resistant rats. DESIGN AND METHODS: Animals were divided into three groups: control (C), fructose fed (F-F), and vanadyl-treated fructose fed (F-T). Control animals were fed with standard chow; F-F and F-T groups fed with 66% fructose diet. F-F and C groups received tap water; F-T group received water supplemented with 0.2 mg/ml vanadyl sulfate. RESULTS: Fasting plasma glucose levels of three groups were comparable. Vanadyl treatment prevented the increase in plasma insulin and TG in the F-T group (P < 0.001) compared with the F-F group. Fructose feeding led to a decrease in plasma DHEAS in the F-F group (P < 0.001) compared with the C group. Vanadyl treatment prevented the decrease in plasma DHEAS in the F-T group (P < 0.001) compared with the F-F group. CONCLUSIONS: Our results indicated that the hyperinsulinemia in fructose-fed, insulin-resistant rats is associated with low levels of DHEAS. Vanadyl sulfate probably restores plasma DHEAS, due to the improved insulin action.

The associations between high-density lipoprotein mean particle size and its fatty acid composition.

AIM: High-density lipoprotein (HDL) particles are heterogeneous in their composition, structure and size and may differ in conferring protection against coronary artery disease. The aim of this study is to investigate the associations between HDL size and its fatty acid composition. PATIENTS & METHODS: HDL mean particle size from 140 healthy men was detected by dynamic light scattering methodology and fatty acid composition of HDL was determined by gas chromatography. RESULTS: HDL with smaller size had a higher proportion of saturated fatty acids and lower proportion of unsaturated fatty acids. HDL mean size indicated a negative correlation with palmitic acid (r = -0.17; p < 0.05) and a positive correlation with palmitoleic acid (r = 0.17; p < 0.05), oleic acid (r = 0.23; p < 0.01), arachidonic acid (r = 0.17; p < 0.05) and dihomogamalinoleic acid (r = -0.18; p < 0.05). CONCLUSION: Saturated fatty acids of HDL are inversely assocaited and unsaturated fatty acids are directly associated with HDL mean size.

Liver aspartate transaminase isoenzymes as biomarkers of chronic exposure to chromium(VI).

Exposure to hexavalent chromium compounds is associated with the risk of lung cancer, dermatitis, gastrointestinal ulcers, and other tissue damages. The aim of this study was to compare liver isoenzyme and total serum activities of aspartate aminotransferase (AST) as cytotoxic biomarkers of acute and chronic cytotoxicity of Cr(VI). We investigated the extent of cell damage caused by chromium(VI) in acute (2.5 mg kg(-1)) daily doses administered over five days and chronic (0.25 mg kg(-1) and 0.5 mg kg(-1)) daily doses administered over 15 to 60 days by measuring total AST in serum and low molecular weight AST (LMW-AST) and high molecular weight AST (HMW-AST) activities in thirty liver fractions. We also evaluated the kinetic properties and electrophoretic mobility of the LMW- and HMW-AST isoenzymes in liver subcellular fractions. Liver LMW-AST and total serum AST activities significantly decreased after 15 days of exposure (P<0.05). With continued treatment, AST activity increased by 15.67% (P<0.05). Interestingly, changes in serum AST activity were similar to changes in the liver LMW-AST isoenzyme. Our results confirmed that total serum AST activity may serve as a reliable tissue biomarker for long-term exposures to Cr(VI), but they also suggest that the LMW-AST isoenzyme could be even more sensitive.

Serum paraoxonase 1 activity is associated with fatty acid composition of high density lipoprotein.

INTRODUCTION: Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. METHODS: One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. RESULTS: Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω 6 fatty acids of HDL. CONCLUSION: The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

Effect of estrogen receptor ß A1730G polymorphism on ABCA1 gene expression response to postmenopausal hormone replacement therapy.

The estrogen receptor ß (ERß) mediates the action of estrogen on metabolism of lipids and lipoprotein. Therefore, its gene is a promising candidate gene for cardiovascular disease. The aim of the present study was to investigate whether the ERß A1730G polymorphism modifies the metabolic response to hormone replacement therapy (HRT) in postmenopausal women. The population included 60 normolipidemic postmenopausal women with equal numbers of each A1730G genotype followed during a 90-day experimental period. All subjects received oral estrogen together with a progestin therapy during the HRT. ABCA1 gene expression and serum lipid and lipoprotein concentrations were measured at the beginning and end of the HRT trial. At baseline, ABCA1 gene expression, lipid or lipoprotein concentrations were not significantly different among the ERß A1730G genotype groups. After HRT, however, subjects with GG genotype had a greater increase in ABCA1 gene expression (p = 0.002) and a trend toward greater increase in apoA-I (p = 0.058) than subjects carrying the A allele. An interaction effect between genotype and HRT effect was observed on ABCA1 gene expression. In conclusion, the positive changes of ABCA1 gene expression and apoA-I were affected by the ERß A1730G polymorphism in women taking estrogen-progesterone therapy.

Kinetic investigation of myeloperoxidase upon interaction with copper, cadmium, and lead ions.

BACKGROUND: Myeloperoxidase (MPO), which is abundantly expressed in neutrophils, catalyzes the formation of a number of reactive oxidant species. However, evidence has emerged that MPO-derived oxidants contribute to tissue damage and initiation and propagation of inflammatory diseases, particularly, cardiovascular diseases. Therefore, studying the regulatory mechanisms of the enzyme activity is of great importance. For clarifying some possible mechanism of the enzyme activity, kinetic investigations of MPO in the presence of Copper (Cu), Cadmium (Cd), and Lead (Pb) ions were carried out in vitro. METHODS: MPO was partially purified from human white blood cells using ion-exchange and gel-filtration chromatography techniques. Its activity was measured spectrophotometrically by using tetramethyl benzidine (TMB) as substrate. RESULTS: Purified enzyme had a specific activity of 21.7 U/mg protein with a purity index of about 0.71. Cu inhibited MPO activity progressively up to a concentration of 60 mM at which about 80% of inhibition achieved. The inhibition was non-competitive with respect to TMB. An inhibitory constant (Ki) of about 19 mM was calculated from the slope of repot. Cd and Pb did not show any significant inhibitory effect on the enzyme activity. CONCLUSION: The results of the present study may indicate that there are some places on the enzyme and enzyme-substrate complex for Cu ions. Binding of Cu ions to these places result in conformational changes of the enzyme and thus, enzyme inhibition. This inhibitory effect of Cu on the enzyme activity might be considered as a regulatory mechanism on MPO activity.

Effect of titanium on lipoprotein lipase activity in vivo and in vitro.

SUMMARY: Lipoprotein lipase (LPL) is a major lipolytic enzyme in the intravascular metabolism of postprandial triglyceride-rich lipoproteins. This enzyme is synthesized and secreted by tissues and transported to the capillary endothelial surface. Decreased activity of this enzyme is suggested to be involved in arterial sequestration of lipoproteins and thus in the progression of atherosclerosis. Titanium salts are widely used in industry, medicine, and pharmacy for tablet coating, pharmaceuticals and cosmetic products. In this study the effect of titanium on post-heparin LPL activity is reported in vivo and in vitro. METHODS: Groups of Male Wistar rats were administered (i.p) with an acute dose of 2.5 mg/kg titanium chloride for 10 days and a chronic dose of 0.75 mg/kg for 30 and/or 60 days. Blood samples were then collected for LPL assay. For in vitro study, plasma aliquots were incubated in the presence of up to 50 mM titanium and the enzyme activity was measured. RESULTS: Animals exposed to acute dose of titanium showed about 20% reduction in LPL activity, whereas 31% and 36% reductions were observed in animals chronically exposed for 30 and/or 60 days, respectively. Titanium in vitro also led to enzyme inhibition, so that a decrease of 28-53% was seen in the presence of 0.1-50 mM titanium. This inhibition by titanium was potentiated when citrate and/or bicarbonate was present. CONCLUSION: Although the mechanism of titanium effect on LPL activity in vivo and in vitro demands more investigations, the inhibitory effect of titanium ion in vivo should be considered seriously in subjects exposed to this metal ion. Changes in LPL activity may affect whole body lipid metabolism, a condition favorable for development and progression of atherosclerosis.

Effect of some volatile oils on the affinity of intact and oxidized low-density lipoproteins for adrenal cell surface receptors.

Extensive research has shown that a high plasma concentration and oxidation of low-density lipoproteins (LDL) has an important role in atherogenesis. The affinity of LDL to its classic receptor is reduced due to oxidation. Instead, it is taken up by scavenger molecules in macrophages, as a result of which foam cells are formed that have a major role in increasing the subendothelial fat layers of the blood vessels. In the present study the antioxidant effect of eight volatile compounds in plant essences, namely, anethol, eugenol, limonen, linalool, p-cymol, pulegon, thymol, and geraniol, and their effect on the affinities of intact and oxidized (with Cu(+2)) LDL for LDL receptor in sheep adrenal tissue cells in the presence of labeled LDL with fluorescein isothiocynate (FITC) were investigated. The results obtained show that eugenol and thymol have the highest antioxidant effect, on the uptake of LDL (intact and oxidized) by the adrenal cells. The order of the compounds studied with regard to their antioxidant effect on intact and oxidized LDL is as follows: On intact LDL: eugenol > or = thymol > linalool > p-cymol > limonen > geraniol > anethol; on oxidized LDL: thymol > or = eugenol > geraniol > p-cymol > linalool > pulegon. Our findings also show that the compounds, particularly thymol and eugenol, have an antioxidant property and can change the affinity of the LDL particles for the LDL receptor probably due to their lipophylic property. Further research may prove that these compounds can be used clinically, especially in atherosclerotic and hypercholesterolemic cases.