Diosgenin Attenuates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats: Underlying Mechanisms.

OBJECTIVE: Prolonged diabetes mellitus causes impairments of cognition and attentional dysfunctions. Diosgenin belongs to a group of steroidal saponins with reported anti-diabetic and numerous protective properties. This research aimed to assess the effect of diosgenin on beneficially ameliorating learning and memory decline in a rat model of type 1 diabetes caused by streptozotocin (STZ) and to explore its modes of action including involvement in oxidative stress and inflammation. METHODS: Rats were assigned to one of four experimental groups, comprising control, control under treatment with diosgenin, diabetic, and diabetic under treatment with diosgenin. Diosgenin was given daily p.o. (40 mg/kg) for 5 weeks. RESULTS: The administration of diosgenin to the diabetic group reduced the deficits of functional performance in behavioral tests, consisting of Y-maze, passive avoidance, radial arm maze, and novel object discrimination tasks (recognitive). Furthermore, diosgenin treatment attenuated hippocampal acetylcholinesterase activity and malon-dialdehyde, along with improvement of antioxidants such as superoxide dismutase and glutathione. Meanwhile, the hippocampal levels of inflammatory indicators, namely interleukin 6, nuclear factor-κB, toll-like receptor 4, tumor necrosis factor α, and astrocyte-specific biomarker glial fibrillary acidic protein, were lower and, on the other hand, tissue levels of nuclear factor (erythroid-derived 2)-related factor 2 were elevated upon diosgenin administration. Besides, the mushroom-like spines of the pyramidal neurons of the hippocampal CA1 area decreased in the diabetic group, and this was alleviated following diosgenin medication. CONCLUSIONS: Taken together, diosgenin is capable of ameliorating cognitive deficits in STZ-diabetic animals, partly due to its amelioration of oxidative stress, inflammation, astrogliosis, and possibly improvement of cholinergic function in addition to its neuroprotective potential.

Effects of Silver Nanoparticle on the Developing Liver of Rat Pups after Maternal Exposure.

The extensive application of silver nanoparticles (AgNPs) has been increased due to their antimicrobial properties, however numerous concerns has been arisen about their toxicity potential. Since nanoparticles can cross through the placenta and accumulate in the embryonic organs especially liver, in this study, developmental hepatotoxicity of AgNPs was investigated. Pregnant rats were divided into two groups, vehicle control group and treated group. Treated group received AgNPs (25 mg/Kg) through intra-gastric gavage in a period of gestational days 1-19. Pups were sacrificed after the birth and their livers collected. Histopathology, ICP- mass spectrometry, Spectrophotometric assay, and ELISA were employed to evaluate AgNPs toxicity in the liver of pups. Glutathione peroxidase (GPX) activity and glutathione (GSH) level were significantly decreased and malondialdehyde (MDA) and caspase 9 levels were significantly increased, although there was no significant change in caspase 8 content in the liver of offspring. Fatty degeneration and congested dilated sinusoids were also observed in histo-pathological examination. These results suggest that maternal oral exposure to AgNPs may induce oxidative stress and apoptosis in the liver of their offspring. Further investigations are required to clarify molecular events behind this happening.

Increased membrane lipid peroxidation and decreased Na+/K+-ATPase activity in erythrocytes of patients with stable coronary artery disease.

OBJECTIVES: We aimed to determine erythrocyte membrane lipid peroxidation levels and Na/K-ATPase activity in patients with and without coronary artery disease (CAD) documented by coronary angiography. DESIGN AND METHODS: A total of 144 patients who had undergone coronary angiography were divided into a CAD group (n=82) and a non-CAD group (control group, n=62) according to the results of coronary angiography. Lipid peroxide levels in plasma and the erythrocyte membrane were measured using a fluorimetric method. Total antioxidant status and Na/K-ATPase activity in plasma were determined using spectrophotometric methods. RESULTS: Lipid peroxidation levels were significantly higher in the erythrocyte membrane of CAD patients compared with controls, whereas Na/K-ATPase activity was significantly lower in the erythrocyte membrane of CAD patients compared with controls. The coronary artery scores were correlated positively with membrane lipid peroxidation (r=0.324, P<0.001) and negatively with Na/K-ATPase activity (r=-0.302, P<0.001). CONCLUSION: This study shows that the levels of membrane lipid peroxidation and Na/K-ATPase activity are correlated with the severity of CAD.

Endothelium-dependent Effect of Sesame Seed Feeding on Vascular Reactivity of Streptozotocin-diabetic Rats: Underlying Mechanisms.

Cardiovascular disorders continue to constitute major causes of morbidity and mortality in diabetic patients. In this study, the effect of chronic administration of sesame (Sesamum indicum L) seed feeding was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received sesame seed-mixed food at weight ratios of 3% and 6% for 7 weeks, one week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in sesame-treated diabetic rats (at a ratio of 6%) relative to untreated diabetics and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was also significantly higher in sesame-treated diabetic rats (at a ratio of 6%) as compared to diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME) significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity and sesame treatment significantly reversed the increased MDA content and restored activity of SOD. We thus conclude that chronic treatment of diabetic rats with sesame seed could in a dose-manner prevent some abnormal changes in vascular reactivity through nitric oxide and via attenuation of oxidative stress in aortic tissue and endothelium integrity is necessary for this beneficial effect.

Chronic administration of daidzein, a soybean isoflavone, improves endothelial dysfunction and attenuates oxidative stress in streptozotocin-induced diabetic rats.

The effect of chronic daidzein, a soybean isoflavone, on aortic reactivity of streptozotocin-diabetic rats was studied. Male diabetic rats received daidzein for 7 weeks a week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to PE was significantly lower in daidzein-treated diabetic rats relative to untreated diabetic rats, and endothelium removal abolished this difference. Endothelium-dependent relaxation to ACh was significantly higher in daidzein-treated diabetic rats as compared with diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester and/or indomethacin attenuated it. Two-month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity, and daidzein treatment significantly reversed the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with daidzein could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and prostaglandin-related pathways, and via attenuation of oxidative stress in aortic tissue and endothelium integrity seems essential for this effect.

Impacts of fresh lime juice and peel on atherosclerosis progression in an animal model.

BACKGROUND: The main protective role of antioxidants in the progression of atherosclerosis has been shown in some studies. Therefore, this project evaluated the effects of Citrus aurantifolia (Christm) juice and peel on antioxidant activity and atherosclerosis progression in rabbits receiving a hypercholesterolemic diet. METHODS: Forty white New Zealand male rabbits were randomly allocated to four groups. All groups were on hypercholesterolemic diet for two months. While the first group was considered as the hypercholesterolemic control, groups 2 and 3 (intervention groups) received 5 ml/day lime juice and 1 g/day dried lime peel powder, respectively. Group 4 was fed a normal diet (normal control). Before and after the study, weight was measured and a fasting blood specimen was taken from the rabbits. Serum lipids analyses and antioxidant activity evaluations were then performed. The rabbits' aorta and coronary arteries were separated and the presence of fatty streaks was studied. RESULTS: Comparing to the hypercholesterolemic control group (-25.2 ± 7.0), only the plasma total antioxidant capacity change was significantly more in rabbits supplemented with lime juice (16.3 ± 14.7) and peel (8.6 ± 7.1) (P = 0.008). The presence of fatty streaks in coronary arteries and aorta of the intervention groups [juice (0.2 ± 0.01); peel (0.0 ± 0.00)] was significantly decreased compared to the hypercholesterolemic control group (1.2 ± 0.4) (P < 0.001). CONCLUSION: Based on our findings, Citrus aurantifolia peel and juice increase plasma antioxidant capacity in rabbits, and can thus prevent or decelerate the process of atherogenesis. However, lime peel is more effective than lime juice.

Is Friedewald formula a good estimation for low density lipoprotein level in Iranian population?

OBJECTIVE: Serum low density lipoprotein (LDL) level is an important biomarker for coronary artery disease (CAD). As direct LDL measurement is expensive and not cost effective, especially in a large population, it is estimated by Friedewald formula. Therefore, we decided to compare the direct LDL measurement method with LDL measured by Friedewald formula in a large general population for the first time in Iran. Furthermore, we examined the association of total cholesterol (TCh), triglyceride (TG), and high density lipoprotein (HDL) with LDL. SUBJECTS AND METHODS: This study was conducted on the subjects, aged 11-97 years, in the third phase of Isfahan Healthy Heart Program (IHHP) from three cities: Isfahan, Najafabad, and Arak. A fasting blood sample was taken from all subjects and referred to Isfahan Cardiovascular Research Center (ICRC) laboratory (central laboratory of IHHP) to assess TCh, TG, HDL, and LDL directly. Also, the LDL level was calculated by Friedewald formula, in addition. RESULTS: The mean level of LDL by direct method was lower than that calculated by Friedewald formula. The mean difference between the two methods was significant, which was 6.6 ± 15.5 mg/dl difference (t = -42.925, P < 0.0001). There was strong correlation between direct and calculated LDL levels (adjusted R(2) = 80.4%). Using regression model, a new formula was found for the estimation of LDL. CONCLUSION: It is concluded that the Friedewald formula overestimates the LDL level compared to the direct method in general Iranian population. It is suggested that LDL measurement be carried out directly, especially in high-risk people. If a formula is necessary for LDL estimation, it is better to obtain an especial formula for each population.

Validity and reproducibility of a food frequency questionnaire for assessment of fruit and vegetable intake in Iranian adults(*).

BACKGROUND: This study's aim was to design and validate a semi-quantitative food frequency questionnaire (FFQ) for assessment of fruits and vegetables (FV) consumption in adults of Isfahan by comparing the FFQ with dietary reference method and blood plasma levels of beta-carotene, vitamin C, and retinol. METHODS: This validation study was performed on 123 healthy adults of Isfahan. FV intake was assessed using a 110-item FFQ. Data collection was performed during two different time periods to control for seasonal effects, fall/winter (cold season) and spring/summer (warm season). In each phase a FFQ and 1 day recall, and 2 days of food records as the dietary reference method were completed and plasma vitamin C, beta-carotene and retinol were measured. Data was analyzed by Pearson or Spearman and intraclass correlations. RESULTS: Serum Lipids, sex, age, body mass index (BMI) and educational level adjusted Pearson correlation coefficient of FV with plasma vitamin C, beta-carotene and retinol were 0.55, 0.47 and 0.28 in the cold season (p < 0.05) and 0.52, 0.45 and 0.35 in the warm season (p < 0.001), respectively. Energy and fat intake, sex, age, BMI and educational level adjusted Pearson correlation coefficient for FV with dietary reference method in the cold and warm seasons were 0.62 and 0.60, respectively (p < 0.001). Intraclass correlation for reproducibility of FFQ in FV was 0.65 (p<0.001). CONCLUSIONS: The designed FFQ had a good criterion validity and reproducibility for assessment of FV intake. Thus, it can serve as a valid tool in epidemiological studies to assess fruit and vegetable intake.

Antioxidant effects of Citrus aurantifolia (Christm) juice and peel extract on LDL oxidation.

BACKGROUND: We studied the antioxidant effects of fresh juice and peel extract of Citrus aurantifolia (Christm). METHODS: Low density lipoprotein (LDL) was separated from one hypercholesterolemic human serum by modified Bronzert and Brewer procedure. Oxidation of LDL was measured at 234 nm against 0, 5, 10, 20, 25, 30 and 40 µl of fresh lime juice and 0, 5, 10, 15 and 20 µl of peel polyphenolic extract solution in DMSO. RESULTS: 5 µl of lime juice didn't change LDL oxidation. 10 µl of juice inhibited LDL oxidation, and with increasing the juice concentration, LDL was oxidized faster. The higher concentrations of peel extract prevented LDL oxidation better than the lower ones. CONCLUSIONS: Both juice and peel demonstrated antioxidant properties, but the excessive consumption of lime juice seems not to be beneficial. Regarding the intensity and type of flavonoids, lime juice and peel may show different effects.

Effect of hydrogenated, liquid and ghee oils on serum lipids profile.

BACKGROUND: Trans fatty acids are known as the most harmful type of dietary fats, so this study was done to compare the effects of hydrogenated, liquid and ghee oils on serum lipids profile of healthy adults. METHODS: This study was a randomized clinical trial conducted on 129 healthy participants aged from 20 to 60 years old who were beneficiaries of Imam-e-Zaman charitable organization. Subjects were randomly divided into 3 groups and each group was treated with a diet containing cooking and frying liquid, ghee, or hydrogenated for 40 days. Fasting serum lipids, including total cholesterol (TC), triglyceride (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), apoprotein A (Apo A), and apoprotein B (Apo B) were measured before and after the study. RESULTS: TC, TG and Apo B had a significant reduction in the liquid oil group compared to the hydrogenated oil group. In the ghee group TG declined and Apo A increased significantly (P < 0.01). Liquid oil group had a significant reduction in HDL-C, compared to the ghee oil group (P < 0.05). CONCLUSION: It was concluded that consuming liquid oil along with frying oil caused to reduce all serum lipid levels. However, ghee oil only reduced TG and increased HDL-C levels.

Obesity and cardiometabolic risk factors in a representative population of Iranian adolescents and adults in comparison to a Western population: the Isfahan Healthy Heart Programme.

OBJECTIVE: The aim of the present study was to develop reference data for the Iranian population for anthropometric values and cardiometabolic data in comparison with those in Americans, as representative of a Western population. DESIGN: The present cross-sectional survey, conducted as part of the baseline survey of a community-based interventional study (the Isfahan Healthy Heart Programme), used a two-stage clustering design and was conducted in 12 600 randomly selected adults (> or =19 years of age) and 2000 adolescents (aged 11-18 years) living in three cities in the central part of Iran. For comparison with a Western population, comparable data for Americans were derived from the data sets of the Second and Third National Health and Nutrition Examination Surveys (NHANES II and NHANES III). RESULTS: Iranian women had significantly higher mean BMI, waist circumference (WC), hip circumference (HC) and waist:hip ratio (WHR) than Iranian men and American women; but the mean BMI of Iranian men was lower than that of American men. The mean serum TAG level of Iranian men was significantly higher than that of Iranian women, whereas the mean serum total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were significantly higher in Iranian women than in men. The Iranian population had lower mean TC, LDL-C and TAG levels than the Americans, but such difference was not documented for HDL-C. Iranian adolescents had significantly lower mean BMI and higher mean TAG than did American adolescents. CONCLUSIONS: Our findings provide serious evidence for health professionals and policy makers about the very high prevalence of generalized and abdominal obesity in Iran. Controlling this emerging health problem, notably in women, should become a national priority in Iran and necessitates comprehensive public health programmes.

Effect of opium addiction on new and traditional cardiovascular risk factors: do duration of addiction and route of administration matter?

BACKGROUND: There is a belief among some society that opium has a number of beneficial effects on cardiovascular disease. The aim of the present investigation as a cross-sectional study was to assess this hypothesis. Several biochemical factors (Fasting blood sugar, Cholesterol, Triglyceride, LDL-Cholesterol, HDL-Cholesterol, HbA1C, CRP, Fibrinogen, Factor VII, SGOT, SGPT, Lpa, apo A and apo B were evaluated in opium-addicted men (case) against non opium-addicted men(control). Three hundred and sixty opium-addicted men were divided into three groups according to the route of administration (Orally, Vafour and Sikh-Sang) and each group was divided into four subgroups according to the duration of addiction (5 months, 1 year, 2 years and 5 years). Blood morphine concentration was measured by ELISA method. RESULTS: The results show that morphine concentration was significantly higher in orally administration. In all routes, there was a direct correlation between blood morphine concentration and period of addiction. Regardless to the period and route of administration, the level of HbA1C, CRP, factor VII, Fibrinogen, apo B, Lpa, SGOT, and SGPT were significantly higher in the case subjects as compared with controls and HDL-Cholesterol and apo a were significantly lower in the case subjects. CONCLUSION: This study demonstrated the deleterious effects of opium on some traditional and new cardiovascular disease risk factors. These deleterious effects are related to the period of addiction and their levels are significantly increased after 2 years of addiction. Route of administration impresses cardiovascular risk factors and "Sikh-Sang" showed the worst effect.

Immunosuppressive activity of a molecule isolated from Artemisia annua on DTH responses compared with cyclosporin A.

Artemisia belongs to the family of Compositea; there are different Artemisias in Iran, of which Artemisia annua L. is grown in the north of Iran. In this study, Artemisinin was extracted and purified from the whole plants. The purification of Artemisinin was performed using column chromatography in different polarities of solvents and the results were evaluated by Thin Layer Chromatography (TLC). (1)H-NMR (NMR-500) spectroscopy was used to characterize the purified Artemisinin. The immunosuppressive activity of Artemisinin was investigated on Balb/c mice by DTH response in comparison to cyclosporin A (CsA). The data indicated that Artemisinin could suppress the delayed type hypersensitivity (DTH) against sheep blood capsule in Balb/c mice. Also its inhibitory effect on calmodulin (CaM) structure was determined by fluorescence spectroscopy. The data indicated an inhibitory effect of that on the activity of calmodulin by increasing the fluorescence emission of calmodulin. Both in vivo (DTH response) and in vitro (spectrofluorometry) studies indicated the activity of Artemisinin as an immunosuppressive agent and that the fluorescence emission of calmodulin is more than cyclosporin A.

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design, methods and initial experience.

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.