Mohsen Ani

The effect of chromium on parameters related to iron metabolism.

The effect of chromium on some parameters related to iron metabolism was investigated. Preliminary experiments showed that this metal ion was taken up by serum proteins and was dependent on the amount of chromium present in the medium. It was also shown that the uptake of iron was reduced significantly in the presence of chromium. In vivo study showed that the serum levels of iron and total iron binding capacity (TIBC) were reduced by 28 and 11%, respectively, following daily administration of chromium (1 mg/kg) for 45 d. Serum ferritin was reduced by 22% under this condition. Hematocrit and hemoglobin levels were also affected in chromium-treated animals and were both reduced by 17%. Spectrophotometric titration of each individual amino acid located in the iron binding site of transferrin revealed that tyrosin might be the most suitable ligand for the binding of chromium to transferrin. These results suggest that chromium may compete with iron in binding to apo-transferrin, and influence iron metabolism and its related biochemical parameters.

Comparative Binding Study of Aluminum and Chromium to Human Transferrin Effect of Iron

The characteristics of aluminum and chromium binding to apotransferrin (apo-tf) have been investigated and compared. Both metal ions were taken up by human transferrin forming complexes with the maximum absorbances at 405 nm for chromium-transferrin (cr-tf) and 240 nm for aluminum-transferrin (Al-tf). In the presence of citric acid, chromium binding to transferrin is five times more than aluminum. The binding of aluminum or chromium to apo-transferrin was reduced by 18 and 22% in the presence of 200 ng/mL of iron. The binding of both metals to apo-tf appears to be pH dependent. In acidic pHs, less chromium and more aluminum binding occurred.

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 ≥ thymol > linalool >p-cymol > limonen > geraniol > anethol; on oxidized LDL: thymol ≥ 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. (Mol Cell Biochem 267: 59–66, 2004)

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.

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.

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 ω6 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 β A1730G Polymorphism on ABCA1 Gene Expression Response to Postmenopausal Hormone Replacement Therapy

The estrogen receptor β (ERβ) 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 ERβ 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 ERβ 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 ERβ A1730G polymorphism in women taking estrogen-progesterone therapy.

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.

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.

Changes in serum, liver, and brain high and low molecular weight alkaline phosphatase following manganese toxicity in rats

The relationship between manganese (Mn) treatment and changes in the activities of serum, liver, and brain high and low molecular weight alkaline phosphatase (ALP) activity was investigated. Results obtained showed that every other day intrapritoneally injection of 175 µmol kg−1 Mn to male rats for two consecutive weeks produced decreased levels of liver and brain ALP activity, while a serum enzyme activity was significantly elevated. Chronic exposure to 68.7 µmol kg−1 Mn produced a significant fall in liver and brain levels of ALP activity and a rise in serum activity. Using gel filtration chromatography technique with sephacryl S300 showed that, in comparison to control, serum and liver homogenate from Mn-treated groups displayed a significant level of high molecular weight ALP, which might be considered as a potential biomarker for Mn toxicity.