DHA-enriched fish oil reduces insulin resistance in overweight and obese adults.

Adipose tissue inflammation is major factor in the development of insulin resistance (IR). Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are anti-inflammatory bioactive lipids, thus may protect against type 2 diabetes (T2D) development. Previous research has demonstrated a sex-dependent association between LCn-3PUFA and T2D, and evidence suggests LCn-3PUFA may improve IR in a sex-dependent manner. This double-blind, randomized, parallel-arm placebo-controlled study aimed to determine whether DHA-enriched fish oil (FO) supplementation improves IR. Sex-dependent effects were assessed by testing for an interaction between sex and treatment in the multiple regression models. Men and women with abdominal obesity (waist circumference: males, ≥102 cm; females, ≥88 cm) and without diabetes were recruited from the community. Participants (age: 50.9 ± 12.7 years, female: 63.7%, BMI: 32.4 ± 6.6 kg/m2) were randomly allocated to either 2 g FO (860 mg DHA + 120 mg EPA) (intervention, n = 38) or 2 g corn oil (CO) /day (control, n = 35) for 12 weeks in a double-blind randomised controlled trial. A fasting blood sample was collected at 0 and 12 weeks for assessment of IR, glucose and blood lipid profile. Sixty-eight participants completed the intervention. Compared with CO (n = 32), FO (n = 36) significantly reduced fasting insulin by -1.62 µIU/L (95%CI: -2.99, -0.26,) (p = 0.021) and HOMA-IR by -0.40 units (95%CI: -0.78, -0.02, p = 0.038). Higher insulin and HOMA-IR at baseline were associated with greater reductions in the FO group (p < 0.001). There was no interaction between sex and treatment for the change in insulin (p-interactionsex*treatment = 0.816) or HOMA-IR (p-interactionsex*treatment = 0.825). DHA-enriched FO reduces IR in adults with abdominal obesity, however, sex-dependent differences were not evident in this study.

Induction of Metallothionein in Rat Liver by Zinc Exposure: A Dose and Time Dependent Study.

Metallothioneins (MTs) are low molecular weight ubiquitous metalloproteins with high cysteine (thiol) content. The intracellular concentration of zinc (Zn) is tightly regulated and MT plays a crucial role in it. The present study investigates the relationship between the Zn status (as a function of Zn concentration and time) in the rat liver and the occurrence of hepatic MT. For dose dependent study, four experimental groups, one control and three receiving different levels of metal supplementation, were chosen [Group 1 control and Group 2, Group 3, Group 4 receiving subcutaneous dose of 10, 50 and 100 mg of Zn/kg body weight (in the form of ZnSO4·7H2O), respectively]. For the time dependent expression of MT, again four experimental groups, i.e. Group 5 control and Group 6, Group 7, Group 8 receiving 50 mg of Zn/kg body weight (in the form of ZnSO4·7H2O) subcutaneously and sacrificed at different time intervals after last injection i.e. 6, 18, 48 h, respectively were chosen. Isolation of MT was done by using combination of gel filtration and ion exchange chromatography while characterization of MT fraction was carried in the wavelength range 200-400 nm. Expression of MT was studied by using Western blot analysis. The results revealed that the MT expression increases with increasing the dose of Zn administered and maximum at 18 h after last Zn injection. Accumulation of MT with increase dose would help in maintaining the intracellular Zn concentration by its sequestration which further reduces the possibility of undesirable binding of Zn to other proteins significantly and maintains Zn homeostasis. The maximum expression of MT at 18 h is indicative of its half life.

Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein profiles.

BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein profiles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n=26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P=0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL (P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was significantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA.

Protective role of Aloe vera against X-ray induced testicular dysfunction.

The present investigation was carried out to evaluate the possible radioprotective potential of an Aloe vera extract against whole-body X-ray irradiation-induced testicular alterations in mice. Male balb/c mice were divided into four groups: control, A. vera, X-ray and A. vera pre-treated + X-ray irradiated. Histopathological examination revealed significant structural alterations in testes after X-ray exposure, which was also associated with the presence of apoptotic cells as assessed by TUNEL assay. X-ray irradiation resulted in elevation in the levels of reactive oxygen species, lipid peroxidation, a reduction in glutathione concentration and enhanced activities of antioxidant enzymes such as glutathione reductase, glutathione peroxidase, catalase, superoxide dismutase and glutathione-S-transferase. Sperm count/motility and testosterone levels were significantly decreased in the irradiated group. Irradiated animals pre-treated with A. vera extract revealed an improvement in antioxidant status, inhibition of lipid peroxides, apoptotic cell formation and enhanced testicular parameters when compared to the X-ray-exposed group. These findings suggest that A. vera extract could ameliorate X-ray-induced damage due to its free radical scavenging properties and its potential to boost cellular antioxidant defence machinery.

Effects of dietary saturated and n-6 polyunsaturated fatty acids on the incorporation of long-chain n-3 polyunsaturated fatty acids into blood lipids.

BACKGROUND/OBJECTIVES: Omega-3 polyunsaturated fatty acids (n-3PUFA) are better absorbed when they are combined with high-fat meals. However, the role of different dietary fats in modulating the incorporation of n-3PUFA in blood lipids in humans has not been previously explored. Omega-6 polyunsaturated fatty acids (n-6PUFA) are known to compete with n-3PUFA in the metabolic pathways and for the incorporation into phospholipids, whereas saturated fats (SFA) may enhance n-3PUFA incorporation into tissues. SUBJECTS/METHODS: In a randomized parallel-design trial, we aimed to investigate the long-term effects of n-3PUFA supplementation in subjects consuming a diet enriched with either SFA or n-6PUFA on fatty acid incorporation into plasma and erythrocytes and on blood lipid profiles (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides). RESULTS: Dietary supplementation with n-3PUFA co-administered with SFA for 6 weeks resulted in a significant rise in total cholesterol (0.46±0.60 mmol/L; P=0.020) and LDL-C (0.48±0.48 mmol/L; P=0.011) in comparison with combination with n-6PUFA. The diet enriched with SFA also induced a greater increase in eicosapentaenoic acid (2.07±0.79 vs 1.15±0.53; P=0.004), a smaller decrease in docosapentaenoic acid (-0.12±0.23 vs -0.30±0.20; P=0.034) and a similar increase in docosahexaenoic acid (3.85±1.14 vs 3.10±1.07; P=0.128) percentage in plasma compared with the diet enriched with n-6PUFA. A similar effect was seen in erythrocytes. N-3PUFA supplementation resulted in similar changes in HDL-C and triglyceride levels. CONCLUSIONS: The results suggest that dietary substitution of SFA with n-6PUFA, despite maintaining low levels of circulating cholesterol, hinders n-3PUFA incorporation into plasma and tissue lipids.

Circulating CD36+ microparticles are not altered by docosahexaenoic or eicosapentaenoic acid supplementation.

BACKGROUND AND AIMS: Circulating microparticles (MP) are the source of a plasma derived form of the scavenger receptor CD36, termed soluble (s)CD36, the levels of which correlate with markers of atherosclerosis and risk of cardiovascular disease. Long chain n-3 polyunsaturated fatty acids have cardioprotective effects that we have previously reported to be gender specific. The aim of this study was to determine if dietary docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) supplementation affect circulating CD36 + MP levels, and if this occurs differentially in healthy men and women. METHODS AND RESULTS: Participants (43M, 51F) aged 39.6 ± 1.7 years received 4 weeks of daily supplementation with DHA rich (200 mg EPA; 1000 mg DHA), EPA rich (1000 mg EPA; 200 mg DHA), or placebo (sunola) oil in a double-blinded, randomised, placebo controlled trial. Plasma CD36 + MP were enumerated by flow cytometry and differences between genders and treatments were evaluated by Student's or paired t-test and one way ANOVA. Males and females had similar levels of CD36 + MP at baseline (mean = 1018 ± 325 vs 980 ± 318; p = 0.577) and these were not significantly changed after DHA (M, p = 0.571; F, p = 0.444) or EPA (M, p = 0.361; F, p = 0.901) supplementation. Likewise, the overall percent change in these levels were not different between supplemented cohorts compared to placebo when all participants were combined (% change in CD36 + MP: DHA = 5.7 ± 37.5, EPA = -3.4 ± 35.4, placebo = -11.5 ± 32.9; p = 0.158) or stratified by gender (M, DHA = -2.6 ± 30.6, EPA = -15.1 ± 20.1, placebo = -21.4 ± 28.7, p = 0.187; F, DHA = 11.7 ± 41.5, EPA = 6.8 ± 42.9, placebo = -2.8 ± 34.7, p = 0.552). CONCLUSION: The cardioprotective effects of DHA and EPA do not act through a CD36 + MP mechanism.

Saturated fat consumption may not be the main cause of increased blood lipid levels.

Consumption of foods rich in saturated fatty acids (SFA) has often been associated with elevated blood lipid levels and consequently with risk for chronic diseases, including coronary heart disease. However, epidemiological and interventional studies on this topic are contradictory. While some studies have established a positive link, other studies have failed to show a significant association between saturated fat consumption and blood lipid levels, and others have even found an inverse association. Moreover, studies using animal models have demonstrated that dietary saturated fats raise blood lipid (cholesterol and triglycerides) levels only when the diet is deficient in omega-3 polyunsaturated fatty acids (n-3PUFA). The n-3PUFA are known for their potential in the management of hyperlipidaemia for the prevention of coronary heart disease, as well as for their anti-arrhythmic, anti-aggregatory and anti-inflammatory potential. We believe that with an adequate consumption of n-3PUFA dietary saturated fat may not result in elevated blood lipid levels. Therefore, we critically evaluated the literature regarding saturated fat and blood lipid level, with an emphasis on the role of n-3PUFA on this relationship. Evidence from animal studies and few clinical trials lead to the hypothesis that there are beneficial or neutral effects of saturated fatty acids when combined with recommended levels of n-3PUFA in the diet. However, an intervention focusing on the background fat when the volunteers' diet is supplemented with n-3PUFA is yet to be done. Proving the authenticity of this hypothesis would mean a substantial change in public health messages regarding saturated fats and their health effects; and also a change in the strategies related to prevention of chronic cardiac and artery diseases.

A comparative validation of a child food frequency questionnaire using red blood cell membrane fatty acids.

BACKGROUND/OBJECTIVES: There are limited validated tools available for the assessment of dietary intake in pediatric populations. This report describes a comparative validation study of selected fatty acid intakes in children assessed by food frequency questionnaire (FFQ), compared with erythrocyte membrane fatty acids. SUBJECTS/METHODS: Overall, 46 overweight and 47 healthy-weight children aged 5-12 years (mean±SD, 9.1±1.3years, body mass index 20.5±4.0) were recruited; dietary fatty acid intakes assessed by parent report using a 135-item semi-quantitative FFQ, were compared with selected child erythrocyte membrane fatty acids assessed from fasting samples using gas chromatography. Spearman's rank correlation coefficients were calculated between fatty acid intake estimates (% of energy) and erythrocyte membrane concentrations (%mol/mol). RESULTS: Significant correlations were found between dietary and erythrocyte eicosapentanoic acid (EPA) concentration (r=0.24, P<0.05) with a statistical trend for total omega three (∑n-3) fatty acids (r=0.22, P=0.06) and linoleic acid (r=0.32, P=0.07) in the healthy-weight children only. CONCLUSION: Parental report of selected child fatty acid intakes using an FFQ can be used to provide an estimate of child intake of EPA, but further work is required to quantify this relationship for other fatty acids and in other populations.

Gender-specific inhibition of platelet aggregation following omega-3 fatty acid supplementation.

BACKGROUND AND AIMS: Increased platelet aggregation is a major risk factor for heart attacks, stroke and thrombosis. Long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA; eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) reduce platelet aggregation; however studies in the published literature involving EPA and/or DHA supplementation have yielded equivocal results. Recent in vitro studies have demonstrated that inhibition of platelet aggregation by LCn-3PUFA is gender specific. We examined the acute effects of dietary supplementation with EPA or DHA rich oils on platelet aggregation in healthy male and females. METHODS AND RESULTS: A blinded placebo controlled trial involving 15 male and 15 female subjects. Platelet aggregation was measured at 0, 2, 5 and 24 h post-supplementation with a single dose of either a placebo or EPA or DHA rich oil capsules. The relationship between LCn-3PUFA and platelet activity at each time point was examined according to gender vs. treatment. EPA was significantly the most effective in reducing platelet aggregation in males at 2, 5 and 24 h post-supplementation (-11%, -10.6%, -20.5% respectively) whereas DHA was not effective relative to placebo. In contrast, in females, DHA significantly reduced platelet aggregation at 24 h (-13.7%) while EPA was not effective. An inverse relationship between testosterone levels and platelet aggregation following EPA supplementation was observed. CONCLUSION: Interactions between sex hormones and omega-3 fatty acids exist to differentially reduce platelet aggregation. For healthy individuals, males may benefit more from EPA supplementation while females are more responsive to DHA.

Omega-3 index, obesity and insulin resistance in children.

OBJECTIVES: Recent studies in adults have suggested that the plasma level of omega-3 fatty acids may be associated with weight status and abdominal adiposity, limited studies exist in paediatric populations. The present study examined the relationship between the omega-3 index, weight status and insulin resistance in children. METHODS: School-age children between 5-12 years, classified as non-obese or obese on the basis of body mass index (BMI) z-scores, were examined. Fat intake was assessed using a parent reported 135-item semi-quantitative food frequency questionnaire. Erythrocyte fatty acid composition was determined using gas chromatography. The Omega-3 index (O3I) was calculated by adding eicosapentaenoic and docosahexaenoic acid % (weight/weight) values. RESULTS: Obese children had altered erythrocyte fatty acid composition unrelated to reported dietary intake. A greater proportion of obese (BMI z-score > 2.25) children (33%) had an omega-3 index of < 4.0 (high risk) compared with non-obese children (BMI z-score < 2.25) (17%). Simultaneously, the number of children with a higher omega-3 index (6.0-8.0 lower risk) was lower in the obese (13%) versus non-obese children (25%, respectively). A moderate, but statistically significant correlation was found between O3I and fasting insulin level (r = -0.3, P = 0.03) and with homeostatic model assessment (HOMA) scores (r = -0.3, P = 0.04). CONCLUSION; The observed association between the omega-3 index, weight status and insulin resistance in children highlights the importance of omega-3 fatty acids in the prevention of obesity-related chronic diseases in later life. The results presented merits confirmation in a larger sample of obese children.

Influence of extraneous supplementation of zinc on trace elemental profile leading to prevention of dimethylhydrazine-induced colon carcinogenesis.

Trace elemental analyses of cancerous tissue is a less explored field of inquiry in cancer research. If the deficiency or excess of a particular trace element can be linked to the cancer, studies can be initiated to see its controlled administration to check the growth of cancer. The present study explored the prophylactic potential of zinc in experimental colon carcinogenesis and also its interaction with other trace metals, which gets altered during the development of colon cancer. Rats were segregated into four groups viz., normal control, dimethylhydrazine (DMH) treated, zinc treated, DMH+zinc treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/Kg body weight) dissolved in 1 mM EDTA-normal saline (pH 6.5), for 8 and 16 weeks, respectively. Zinc was supplemented at a dose level of 227 mg/L in drinking water, for 8 and 16 weeks. The elemental analyses of colonic samples were carried out using Energy Dispersive X-Ray Fluorescence technique (EDXRF). Zinc administration to DMH treated rats significantly decreased the tumor incidence, tumor multiplicity with simultaneous decrement in tumor size. EDXRF studies revealed that the concentrations of the elements zinc, chromium, manganese and copper were decreased, whereas the concentration levels of iron were found to be increased in the colon tissues following 8 and 16 weeks of DMH treatment. However, zinc supplementation to DMH-treated rats significantly improved the altered levels of elements when compared to DMH-treated animals indicating the chemopreventive role of zinc. In conclusion, DMH induced colon carcinogenesis is accompanied by altered trace element profile and zinc has a positive beneficial effect against chemically-induced colonic carcinogenesis.

An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals.

High sensitivity C-reactive protein (hs-CRP) is a marker of low-grade sustained inflammation. Omega-3 (n-3) fatty acids have anti-inflammatory properties and are associated with reduced cardiovascular disease (CVD) risk. The aim of this study was to investigate whether plasma n-3 fatty acid concentration is related to hs-CRP concentration. A total of 124 free-living adults, were divided into tertiles of plasma hs-CRP (<1.0, 1.0-3.0 and >3.0 mg/l). Body composition and anthropometric measurements were recorded. Hs-CRP was analysed using immunoassays and fatty acids were measured by gas chromatography. Plasma hs-CRP concentration was negatively correlated with total n-3 fatty acids (P=0.05), eicosapentaenoic acid (EPA; P=0.002) and docosapentaenoic acid (DPA; P=0.01). The highest hs-CRP tertile (>3.0 mg/l) had significantly lower concentrations of total n-3 fatty acids, EPA and DPA, when compared with the other tertiles (P<0.05). This study provides evidence that in healthy individuals, plasma n-3 fatty acid concentration is inversely related to hs-CRP concentration, a surrogate marker of CVD risk.

Reduced mania and depression in juvenile bipolar disorder associated with long-chain omega-3 polyunsaturated fatty acid supplementation.

Long-chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) supplementation may improve symptoms of depression in children and bipolar disorder (BD) in adults. No studies have examined the effectiveness of LCn-3PUFA supplementation in the treatment of mania and depression in juvenile BD (JBD) when given as an adjunct to standard pharmacological treatment. Eighteen children and adolescents with JBD received supplements containing 360 mg per day eicosapentaenoic acid (EPA) and 1560 mg per day docosahexaenoic acid (DHA) for 6 weeks in an open-label study. Intake and fasting red blood cell (RBC) LCn-3PUFA, mania, depression and global function were assessed before and after supplementation. RBC EPA and DHA were significantly higher following supplementation. Clinician ratings of mania and depression were significantly lower and global functioning significantly higher after supplementation. Parent ratings of internalizing and externalizing behaviours were also significantly lower following supplementation. A larger randomized controlled trial appears warranted in this participant population.

Consumption of an n-3 polyunsaturated fatty acid-enriched dip modulates plasma lipid profile in subjects with diabetes type II.

OBJECTIVE: Recent developments in micro-emulsification technology have allowed the fortification of foods with long-chain n-3 polyunsaturated fatty acid (PUFA) without the undesirable fish odour/taste and with reasonable shelf life. The effects of supplementing the diets of people with diabetes type II with a hummus-based dip enriched with long-chain n-3PUFA on plasma fatty acid composition and lipid levels were examined. DESIGN: A pre- and post-intervention study. SETTING: This study was conducted at the University of Newcastle, Australia. SUBJECTS: Participants were recruited via advertisements on the University of Newcastle notice boards and in the local newspapers. Following initial response to study advertisements, information statements were mailed out to 29 potential participants. Thirteen participants were eligible and consented to participate in the trial. There were no dropouts as all the 13 participants completed 6-week intervention trial. METHODS: Free-living male and female subjects with diabetes type II (n=13) consumed the n-3PUFA-enriched dip for a period of 6 weeks. Fasting blood samples were collected pre- and post-intervention for analyses of fatty acids and plasma lipids. RESULTS: Following 6 weeks of consuming the enriched dip, all the long-chain n-3PUFA (20:5n-3, 22:5n-3 and 22:6n-3) were significantly (P<0.05) elevated in the plasma lipids. This represented an increase in 20:5n-3 content by 117%, an increase in 22:5n-3 content by 15% and an increase in 22:6n-3 content by 80% over the baseline values before dip consumption. A significant reduction (P<0.05) in the plasma triglyceride levels from 1.93 (1.08-2.09) mmol/l at baseline to 1.27 (0.93-2.22) mmol/l after 6 weeks was also apparent following the consumption of the n-3PUFA-enriched dip. Plasma cholesterol was unchanged; however, low-density lipoprotein (LDL)-cholesterol (2.46+/-0.21 versus 2.72+/-0.22 mmol/l, P<0.034) and high-density lipoprotein (HDL)-cholesterol (1.16+/-0.09 versus 1.22+/-0.09 mmol/l, P<0.042) were significantly increased following the dietary intervention. CONCLUSIONS: These results demonstrate that n-3PUFA are readily bioavailable from the fortified dip matrix and alter the plasma lipid profile.

Hepatoprotective role of zinc in lead-treated, protein-deficient rats.

The current study was designed to evaluate the hepatoprotective role of zinc after lead (Pb) treatment of protein-deficient (PD) rats. The animals were subjected to seven different treatment groups: G-1 (normal control, 18% protein), G-2 (protein-deficient, 8% protein), G-3 (Pb-treated, 100 mg/kg body weight of lead acetate), G-4 (Zn-treated, zinc sulfate at a dose level of 227 mg/L drinking water), G-5 (PD + Pb-treated), G-6 (PD + Zn-treated), and G-7 (PD + Pb + Zn-treated). Serum albumin levels and total serum protein contents were estimated to assess the severity of protein deficiency at the end of 8 weeks in all the treatment groups. Also, the study explored the role of zinc on antioxidative defense system enzymes in liver of protein-deficient rats subjected to lead toxicity treatment. Further, the study was extended to elucidate the levels of zinc and lead in liver tissue after different treatments of rats using positron-induced X-ray emission technique (PIXE). The current study indicated a significant change in the levels of various antioxidative enzymes and serum albumin as well as total protein contents of protein-deficient rats subjected to lead treatment. A significant increase in the levels of malondialdehyde (MDA), catalase, and glutathione peroxidase (GPx) was seen after 8 weeks of lead treatment of protein-deficient rats. On the contrary, levels of albumin, total protein content, superoxide dismutase (SOD), GSH, were found to be decreased. Interestingly, zinc supplementation has tended to normalize the altered levels of these enzymes to a significant extent. The levels of zinc in liver tissue was found to be decreased significantly in protein-deficient as well as lead-treated rats. However, hepatic zinc concentration was increased to a significant extent in protein-deficient rats supplemented with zinc when compared with protein-deficient rats. Further, the presence of lead was also observed in livers of lead-treated animals. In conclusion, the study revealed the antioxidative role of zinc in hepatotoxic conditions induced by subjecting the rats to protein-deficient diet and lead treatment.

Time dependent study to evaluate the efficacy of zinc on hepatic marker enzymes and elemental profile in serum and liver of protein deficient rats.

This study was designed to determine the time dependent protective effects of zinc sulfate on the serum and liver marker enzymes along with elemental profile in protein deficient Sprague Dawley (S.D.) female rats. Zinc sulfate in the dose of 227 mg/l in drinking water was administered to normal control as well as protein deficient rats for a total duration of 8 weeks. The effects of different treatments were studied on enzymes like alkaline phosphatase (ALP), aspartate aminotransferases (AST) and alanine aminotransferases (ALT) in rat serum at different time intervals of 1, 2, 4 and 8 weeks and in the rat liver at the end of study. The status of different essential elements in liver was also studied. The serum ALP activity got significantly depressed when estimated at the intervals of 4 and 8 weeks. Activity of serum ALT was significantly increased after 4 weeks interval in protein deficient rats and the increasing trend continued upto 8 weeks of protein deficiency. On the other hand, activity of AST showed a significant increase just after 2 weeks and activity continued to be increased up to 8 weeks. Moreover activities of all the hepato marker enzymes showed a significant increase in liver of protein deficient rats. Interestingly, supplementation of Zn to protein deficient rats helped in regulating the altered activities of ALP, AST and ALT both in serum and liver. However, zinc treatment alone to normal rats did not indicate any significant change in the activities of all the enzymes in liver as well serum except at the interval of 2 weeks where a marginal increase in the activity of AST was seen. It has also been observed that concentrations of zinc, copper, iron and selenium were found to be decreased significantly in protein deficient animals. However, the levels of these elements came back to within normal limits when zinc was administered to protein deficient rats.

Role of zinc in regulating the levels of hepatic elements following nickel toxicity in rats.

This study was designed to determine the protective effects of zinc on the hepatotoxicity induced by nickel in rats. Female Sprague-Dawley (SD) rats received either nickel sulfate alone in the dose of 800 mg/L nickel in drinking water, zinc sulfate alone in the dose of 227 mg/L zinc in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. The effects of different treatments were studied on activities of rat liver marker enzymes like alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferases (AST) and on the status of essential elements in rat liver. The study revealed a significant increase in the activities of enzymes ALP and ALT in rats subjected to nickel treatment. Interestingly, zinc supplementation to rats treated with nickel brought back the raised activities of these enzymes to within normal limits. Further, the levels of elements in liver that include zinc, copper, selenium, and potassium were found to be significantly suppressed following nickel treatment, whereas the levels of iron and sulfur were elevated. However, zinc treatment alone did not cause any appreciable change in the concentration of these elements. To the contrary, when zinc was given to nickel-treated rats, the concentrations of zinc, copper, potassium, and phosphorus were not significantly different from that of normal controls, whereas the levels of iron, selenium, and sulfur were improved in comparison to nickel-treated rats but were not within the normal limits. The present study concludes that zinc has the ability to maintain the levels of hepatic elements and has bearing in regulating the liver functions by maintaining the activities of marker enzymes in conditions of nickel toxicity.

Effect of zinc on biological half-lives of 65Zn in whole body and liver and on distribution of 65Zn in different organs of rats following nickel toxicity.

This study was designed to determine the effect of zinc on the biological half-lives of 65Zn in whole body and liver and on distribution of 65Zn in different organs of rats following nickel toxicity. Sprague-Dawley (SD) rats received either nickel in the form NiSO4.6H2O at a dose of 800 mg/L in drinking water, zinc in the form of ZnSO4.7H2O at a dose of 227 mg/L in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. All of the rats were injected with a tracer dose of 0.37 MBq 65Zn at the end of the treatment period. The effects of different treatments were studied on biological half-lives of 65Zn in whole body and liver and on the distribution of 65Zn in different organs of rats. In the present study, we have noted that nickel treatment to normal rats caused a significant decrease in the slow component (Tb2) in liver, which improved following zinc supplementation. Nickel administration to normal-diet-fed animals caused significant lowering in the percentage uptake of 65Zn values in the brain, liver, and intestine. However, the administration of zinc to nickel-treated rats improved the status of 65Zn in different organs. The Tb2 in the liver and the percentage uptake of 65Zn values elevated following zinc supplementation to nickel-treated rats.

Protective role of zinc in nickel induced hepatotoxicity in rats.

This study was planned to determine the protective role of zinc, if any, in attenuating the toxicity induced by nickel sulfate in rat liver. Female Sprague Dawley (SD) rats received either nickel alone in the dose of 800 mg/l in drinking water, zinc alone in the dose of 227 mg/l in drinking water, and nickel plus zinc or drinking water alone for a total duration of eight weeks. The effects of different treatments were studied on various parameters in rat liver which include antioxidant enzymes, levels of nickel and zinc and histoarchitecture at the light microscopic level. Further, the activities of hepatic marker enzymes AST and ALT were also studied in rat serum. Nickel treatment to the normal control animals, resulted in a significant increase in lipid peroxidation and enzyme activities of catalase and glutathione-S-transferase. On the contrary, nickel treatment to normal rats caused a significant inhibition in the levels of reduced glutathione. Superoxide dismutase activity was found to be decreased which however was not significant. Interestingly, when Zn was supplemented to nickel treated rats, the activities of catalase, and glutathione-S-transferase and the levels of GSH and lipid peroxidation came back to within normal limits. Activities of serum AST and ALT were increased significantly following nickel treatment to normal rats. Simultaneous zinc administration to nickel treated rats tended to restore the altered levels of AST and ALT. Normal control and zinc treated animals revealed normal histology of liver. On the other hand, nickel treated animals showed alterations in normal hepatic histoarchitecture which comprise of vacuolization of the hepatocytes and dilatation of sinusoids as well as increase in the number of bi-nucleated cells. Administration of zinc to nickel treated rats resulted in marked improvement in the structure of hepatocytes, thus emphasizing the protective potential of zinc in restoring the altered hepatic histoarchitecture. The nickel administration to normal rats indicated increased concentrations of nickel and decreased concentrations of zinc. However, zinc effectively brought the altered levels of nickel and zinc to within normal range. The study concludes that zinc has the potential in alleviating the toxic effects of nickel in rat liver because of its property to induce metallothionein (S-rich protein) as a free radical scavenger, or its indirect action in reducing the levels of oxygen reactive species.

Dietary n-3 fatty acids alter the contractile response to thromboxane A(2) agonists of porcine coronary arteries.

Dietary supplementation with marine fish oils rich in n-3 fatty acids reduces circulating thromboxane A(2) (TxA(2)). However, the effects on thomboxane A(2) receptor mediated vascular reactivity are uncertain. The aim of this study was to test the hypothesis that dietary modification of TxA(2) levels alters vascular responsiveness to TxA(2) analogues. Juvenile female white pigs were fed a diet enriched in either 5% (w/w) fish oil or beef tallow for 6 weeks. Serum and myocardial tissue levels of eicosapentaenoic and docosahexaenoic acid reached a plateau during this period. Vascular responses were measured in isolated coronary arterial rings with intact endothelium by isometric tension measurement. Arteries from pigs fed fish oil produced a greater maximum vasoconstrictor tension to the TxA(2) analogue U46619 than did rings from pigs fed beef tallow (120 +/- 6% compared to 92 +/- 8%, values represented as a percentage relative to the maximum vasoconstrictor effect obtained to KCl, regression analysis, analysis of variance, P