Biomedical subjects

M L Garg

Publications and source records attributed to M L Garg.

At least 19 recordsLinked to original sources

PubMed2006

Zinc protects rat liver histo-architecture from detrimental effects of nickel.

This study was designed to examine the protective potential of zinc on the histoarchitecture distortion induced by nickel in rats. Male Sprauge Dawley (S.D) rats received either nickel alone in the form NiSO(4) x 6H(2)O at a dose of 800 mg/l in drinking water, zinc alone in the form of ZnSO(4) x 7H(2)O at a dose of 227 mg/l in drinking water, or nickel plus zinc or drinking water alone for a total duration of eight weeks. The effects of different treatments were studied on rat liver histoarchitecture by using both light and transmission electron microscopes. Normal control and zinc treated animals revealed normal histology of liver, however, nickel treated animals resulted in drastic alterations of normal hepatic histoarchitecture, after 8 weeks of treatment. 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 close to the histoarchitecture of normal animals.

Animals↗

PubMed2006

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.

Administration, Oral↗

PubMed2005

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.

Alanine Transaminase↗

PubMed2005

Protective effects of zinc on oxidative stress enzymes in liver of protein-deficient rats.

Persons afflicted with protein malnutrition are generally deficient in a variety of essential micronutrients like zinc, copper, iron, and selenium, which in turn affects number of metabolic processes in the body. To evaluate the protective effects of zinc on the enzymes involved in oxidative stress induced in liver of protein-deficient rats, the current study was designed. Zinc sulfate at a dose level of 227 mg/L zinc in drinking water was administered to female Sprague-Dawley normal control as well as protein-deficient rats for a total duration of 8 weeks. The effects of zinc treatment in conditions of protein deficiency were studied on rat liver antioxidant enzymes, which included catalase, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), glutathione reduced (GSH), and glutathione-S-transferase (GST). Protein deficiency in normal rats resulted in a significant increase in hepatic activities of catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase and the levels of lipid peroxidation. A significant inhibition in the levels of reduced glutathione and the enzyme activity of superoxide dismutase has been observed after protein deficiency in normal rats. Interestingly, Zn treatment to protein-deficient animals lowered already raised activity catalase, glutathione peroxidase, and glutathione-S-transferase and levels of lipid peroxidation to significant levels when compared to protein-deficient animals. Also, Zn treatment to the protein-deficient animals resulted in a significant elevation in the levels of GSH and SOD activity as compared to their respective controls, thereby indicating its effectiveness in regulating their levels in adverse conditions. 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 administrated to protein-deficient rats. This study concludes that zinc has the potential to regulate the activities of oxidative stress enzymes as well as essential hepatic elements.

Animals↗

PubMed2004

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.

Animals↗

PubMed2004

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.

Alanine Transaminase↗

PubMed2004

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.

Animals↗

PubMed2004

Biokinetics of 65Zn in liver and whole body and its bio-distribution in nickel treated protein deficient rats.

This study was designed to determine the effect of nickel treatment on biological half-lives of 65Zn in whole body and liver as well as on distribution of 65Zn in different organs of protein deficient rats. Nickel sulfate at a dose level of 800mg/l in drinking water was administrated to normal control as well as to protein deficient rats for 8 weeks. A significant increase was found in fast and slow components of biological half lives of 65Zn in whole body and only fast component in liver of protein deficient rats. Interestingly, slow component in whole body and fast component in liver of nickel treated protein deficient rats were not different from normal controls though they were significantly elevated in protein deficient rats. On the other hand, slow component of 65Zn was also not altered in nickel treated protein deficient rats, which however, was significantly decreased in nickel treated rats. Protein deficiency led to a marked elevation in per cent uptake of 65Zn in brain and caused significant depression in liver, kidney and intestine. However, uptake of 65Zn in brain showed a significant depression in nickel treated rats, whereas the uptake was elevated in brain in nickel treated protein deficient rats. In conclusion, protein deficient conditions seem to be playing a dominant role in context with the distribution of 65Zn in different organs when nickel is administered to protein deficient rats. However nickel alone is seen to cause adverse effect on the distribution of 65Zn.

Animals↗

PubMed2003

Biomarkers of lipid peroxidation, airway inflammation and asthma.

Oxidative stress, specifically lipid peroxidation, is believed to contribute to the pathophysiology of asthma. This review highlights the pathways through which reactive oxygen species (ROS) may lead to lipid peroxidation. The potential of both the innate and acquired immune systems to activate inflammatory cells and release ROS that may overwhelm the host antioxidant defences and cause lipid peroxidation, accompanied by detrimental pathophysiological effects, are discussed. Despite the evidence demonstrating the importance of lipid peroxidation, systematic characterisation of oxidative stress and antioxidant defences has not been undertaken, largely due to the lack of appropriate biomarkers. This review discusses the emergence of isoprostanes (specifically 8-iso-prostaglandin F2alpha) as reliable, in vivo markers of lipid peroxidation, which provides an appropriate tool for studying oxidative stress. Furthermore, the development of techniques to study induced sputum and breath condensate, derived directly from the airway surface, enables the site of oxidative damage to be closely assessed. Evidence suggests that dietary changes that have occurred over recent years have increased susceptibility to lipid peroxidation, due to reduced antioxidant defences. To date, the limited number of long-term (>1 week) supplementation trials have been promising. However, the development of techniques to study isoprostanes in airway-lining fluid pave the way for further studies investigating the potential for antioxidant supplements to be used as routine therapy in asthma.

Asthma↗

PubMed2001

Oxidative stress in cystic fibrosis: dietary and metabolic factors.

OBJECTIVE: To examine oxidative stress in CF by measuring 8-iso-PGF2alpha and antioxidant defenses, in relation to dietary intake, immune function and clinical status. METHODS: We measured total plasma concentrations of 8-iso-PGF2alpha and dietary antioxidants (vitamin E, vitamin C, beta-carotene), erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase), lung function and dietary intake in 21 CF subjects and 21 healthy age- and gender-matched controls. RESULTS: Total plasma 8-iso-PGF2alpha concentration (median [quartile 1-quartile 3]) was significantly higher in CF subjects compared to controls (214 pg/mL (155-331) vs. 135 pg/mL (101-168), p = 0.001). Neutrophil, monocyte and total white cell counts were elevated in the CF group and these correlated with 8-iso-PGF2alpha concentration. Despite similar dietary intake, lower plasma antioxidant concentrations were observed in the CF group (vitamin E, p < 0.001, vitamin C, p = 0.004, beta-carotene, p = 0.001). 8-iso-PGF2alpha correlated negatively with plasma vitamin E, C and beta-carotene concentrations. CONCLUSION: Oxidative stress is increased in CF patients, despite normal dietary antioxidant intake. The immune response appears to be a key factor causing oxidative stress. Antioxidant intervention aimed at reducing oxidative stress in CF needs to be assessed.

Adolescent↗

PubMed2000

Lipid peroxidation as determined by plasma isoprostanes is related to disease severity in mild asthma.

Oxidlative stress is believed to play an important role in the pathophysiology of asthma. Recently discovered F2-isoprostanes, of which 8-iso-PGF2alpha is the most well-known isomer, have emerged as the most reliable marker of in vivo oxidative stress. The aim of this study was to examine 8-iso-PGF2alpha as a biomarker of oxidative stress in mild asthma in relation to endogenous and dietary antioxidant protection. Total (free and esterified) plasma 8-iso-PGF2alpha, plasma dietary antioxidants (vitamins E and C, Beta-carotene, Zn, and Se), and erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase) were measured in 15 mild asthmatics and 15 age-and sex-matched controls. Total plasma 8-iso-PGF2alpha levels [median (quartile 1 - quartile 3)] were significantly increased in the asthmatics [213 pg/mL (122-455) vs. 139 pg/mL (109-174), P= 0.042]. The 8-iso PGF2alpha levels were found to be associated with clinical asthma severity (P = 0.044) and inhaled corticosteroid use (P = 0.027) in asthmatics. No differences were observed in the plasma dietary antioxidant vitamins. The asthmatics had significantly lower plasma levels of Zn (P = 0.027) and Se (P = 0.006). Plasma Se correlated negatively with 8-iso-PGF2alpha (r = -0.725, P= 0.002). No differences between the groups were observed for glutathione peroxidase or superoxide dismutase, however, superoxide dismutase activity was negatively associated with asthma severity (P = 0.042). In conclusion, oxidative stress is increased in mildly asthmatics, as reflected by increased plasma levels of 8-iso-PGF2alpha and a deficiency in plasma Zn and Se. The isoprostane 8-iso-PGF2alpha may provide a useful tool in intervention studies aimed at improving clinical status in asthma.

Adolescent↗

PubMed2000

Suppression of inositol phosphate release by cardiac myocytes isolated from fish oil-fed pigs.

Fatty acid composition of cardiac myocytes and release of inositol phosphates in pigs fed a fish oil supplemented diet was examined. Two groups of female pigs were fed diets supplemented with either 50 g/kg diet beef tallow (as control) or 50 g/kg diet fish oil (MaxEPA) rich in n-3 fatty acids. After 6 weeks of supplementation, the pigs were anesthetized and hearts were removed. Cardiac myocytes were isolated, lipid extracted and separated into non-polar and polar lipids by thin-layer chromatography. Fatty acid composition of individual neutral and polar lipid classes were examined by gas chromatography. To study the effect of membrane phospholipid modification on the phospholipase C (PLC) mediated release of inositol phosphates, cardiac myocytes were labelled with 4 microCi/mL myo-[2-(3)H]inositol for 48 h. After stimulation with epinephrine and phenylephrine, the water soluble [3H]inositol products were extracted, separated from [3H]inositol and [3H]glycerophosphoinositol by chromatography on Dowex AG 1-X8 and quantitated by scintillation counting. Cardiac myocytes isolated from fish oil-fed pigs had higher levels of n-3 polyunsaturated fatty acid in the non-esterified fatty acid and phospholipid fraction. Similarly, these cardiac myocytes had increased level of n-3 fatty and decreased n-6 fatty acids in all the phospholipid fractions, PE, PC, P1 and PS (p < 0.05). After stimulation, the levels of [3H]inositol trisphosphate (IP3) and [3H]inositol tetrakisphosphate (IP4) in cardiac myocytes isolated from fish oil-fed pigs were significantly reduced (p < 0.05) compared to myocytes isolated from beef tallow fed-pigs. This study for the first time has utilised adult cardiac myocytes to demonstrate the effect of n-3 PUFA supplementation on cardiac myocyte phospholipid fatty acid composition and release of second messengers.

Animals↗

PubMed2000

The eicosapentaenoic to docosahexaenoic acid ratio of diets affects the pathogenesis of arthritis in Lew/SSN rats.

Dietary-induced changes in tissue levels of polyunsaturated fatty acids modify inflammatory reactions through changes in the synthesis of lipid and peptide mediators of inflammation. Four semipurified 20% fat diets, based on beef tallow (BT), safflower oil (SFO), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were provided. The DHA and EPA ratios of the (n-3) fatty acid-based diets were 1.1 and 3.4, respectively. The effect of prefeeding diets differing in EPA to DHA ratios prior to the induction of streptococcal cell wall (SCW) arthritis in female Lew/SSN rats was examined. Weanling rats were fed diets for 5 wk before arthritis induction and 5 wk post-arthritis induction. Footpad thickness, hock circumference, plasma and macrophage fatty acids and histological assessment were compared. There were no differences in food intake and final body weights among the groups. Footpad inflammation, reported as percentage change (adjusted for growth) was greatest for rats fed the BT-based diet, intermediate in those fed the SFO-based diet and least for the rats fed the EPA- and DHA-based diets (P < 0.05). Macrophage phospholipids revealed cellular incorporation of EPA and DHA from the fish-oil based diets which modified lipid and peptide mediators of inflammation. Histological sections of rat hocks ranked by severity of arthritis-related changes suggested that the SFO- and EPA-based diets were more successful in ameliorating the destructive arthritic phase in hock joints than the BT- and DHA-based diets (P = 0.09) in this model of arthritis. The course of SCW-induced arthritis can be altered by diet-induced changes in macrophage fatty acid composition. The EPA-based diet is more effective in suppression of inflammation than the DHA-based diet.

Analysis of Variance↗

PubMed1999

Elevated plasma levels of F2 alpha isoprostane in cystic fibrosis.

Cystic fibrosis (CF) is associated with chronic lung infection, inflammation, and elevated indices of oxidative stress. Recently, isoprostanes were shown to be a reliable in vivo marker of oxidant injury with 8-iso-PGF2 alpha, shown to cause airflow obstruction and plasma exudation in guinea pig lung. The present study was designed to examine the relationship between 8-iso-PGF2 alpha levels, plasma antioxidants, and clinical status in CF. We hypothesized that plasma 8-iso-PGF2 alpha levels would be higher in subjects with CF compared to healthy controls. Plasma 8-iso-PGF2 alpha levels were prospectively measured in 22 subjects with CF and nine healthy controls using an 8-isoprostane enzyme immunoassay kit along with plasma vitamins A, E, and beta-carotene. Plasma 8-iso-PGF2 alpha levels were shown to be significantly elevated in the CF subjects compared to controls (319.6 +/- 52.6 vs. 145.0 +/- 21.0 pg/mL, P = 0.005). Plasma levels of antioxidants were significantly lower for the CF subjects compared to the controls (vitamin A, P < 0.003; vitamin E, P < 0.001; and beta-carotene, P < 0.01). This study confirms significantly elevated lipid peroxidation in CF using 8-iso-PGF2 alpha levels.

Adolescent↗

PubMed1999

Specific modifications of phosphatidylinositol and nonesterified fatty acid fractions in cultured porcine cardiomyocytes supplemented with n-3 polyunsaturated fatty acids.

Mechanisms for the antiarrhythmic effect of n-3 polyunsaturated fatty acids (PUFA) are currently being investigated using isolated cardiac myocytes. It is still not known whether the incorporation of n-3 PUFA into membrane phospholipids is a prerequisite for its protective action or if n-3 PUFA exert antiarrhythmic effects in their nonesterified form as demonstrated by recent studies. Adult porcine cardiomyocytes were grown in media supplemented with arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). After 24 h, analysis of total lipids showed that the myocytes were enriched with the respective fatty acids compared to control cells. Large proportions of all three fatty acids supplemented (69% AA, 72% DHA, and 66% EPA) remained unesterified. Fatty acid analyses of total phospholipids (PL) revealed that the incorporation of EPA and DHA, though small, was significantly different (P<0.05) from that of the control cells. The PL fraction was further separated into phosphatidylinositol (PI), phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine to study the pattern of incorporation of the fatty acids in these fractions. It became apparent that EPA and DHA were selectively incorporated into the PI fraction. This study demonstrates that in adult porcine cardiomyocytes, the n-3 PUFA supplementation selectively modulates two important lipid fractions, nonesterified fatty acid and PI, which were implicated in the mechanisms of prevention of cardiac arrhythmias.

Animals↗

PubMed1999

Cardiac (n-3) non-esterified fatty acids are selectively increased in fish oil-fed pigs following myocardial ischemia.

The effect of fish oil supplementation on the nonesterified fatty acid (NEFA) concentration and composition in the normoxic and hypoxic myocardium of pigs was examined. Two groups of female pigs (n = 7) were fed a diet supplemented with either 5 g beef tallow/kg (as control) or 5 g fish oil/kg (MaxEPA) rich in (n-3) fatty acids. After 6 wk of supplementation, the pigs were anesthetized, hearts exposed by thoracotomy followed by occlusion of the left anterior descending artery. Normoxic and hypoxic regions of the heart were examined for NEFA concentration and composition by using a combination of thin layer and gas chromatography. Nonesterified (n-6) and (n-3) fatty acid concentration and composition differed significantly between the two groups in both the normoxic and hypoxic areas of the heart. Eicosapentaenoic and docosahexaenoic acid concentration in the NEFA fraction of the normoxic myocardium were higher in the fish oil group than in the beef tallow group (P < 0.001). In the fish oil-fed pigs, the (n-3) NEFA concentration was significantly higher in the hypoxic compared to the normoxic region of the heart. The fish oil-fed group had lower levels of arachidonic acid in the NEFA fraction compared to the beef tallow-fed group, whereas the hypoxic myocardium had higher levels of arachidonic acid, regardless of the dietary fat supplementation. Despite large differences in the proportions of saturated fatty acids in the experimental diets, there was little or no difference in the saturated fatty acid content of cardiac phospholipid and NEFA fractions. Following myocardial ischemia, (n-3) fatty acids in the NEFA fractions were selectively increased in the fish oil-fed pigs, implicating the possible role of nonesterified (n-3) polyunsaturated fatty acids in the prevention of arrhythmias.

Animals↗

PubMed1997

Prevention of cardiac arrhythmia by dietary (n-3) polyunsaturated fatty acids and their mechanism of action.

The role of marine fish oil (n-3) polyunsaturated fatty acids in the prevention of fatal ventricular arrhythmia has been established in experimental animals. Prevention of arrhythmias arising at the onset of ischemia and reperfusion is important because if untreated, they result in sudden cardiac death. Animals supplemented with fish oils in their diet developed little or no ventricular fibrillation after ischemia was induced. Similar effects have also been observed in cultured neonatal cardiomyocytes. Several mechanisms have been proposed and studied to explain the antiarrhythmic effects of fish oil polyunsaturated fatty acids, but to date, no definite mechanism has been validated. The sequence of action of these mechanisms and whether more than one mechanism is involved is also not clear. Some of the mechanisms suggested to explain the antiarrhythmic action of fish oils include the incorporation and modification of cell membrane structure by (n-3) polyunsaturated fatty acids, their direct effect on calcium channels and cardiomyocytes and their role in eicosanoid metabolism. Other mechanisms that are currently being investigated include the role of (n-3) polyunsaturated fatty acids in cell signalling mediated through phosphoinositides and their effect on various enzymes and receptors. This article reviews these mechanisms and the antiarrhythmic studies using (n-3) polyunsaturated fatty acids.

Animals↗

PubMed1997

Increased saturated triacylglycerol levels in plasma membranes of human neutrophils stimulated by lipopolysaccharide.

Neutrophils isolated from patients with bacterial infections or stimulated in vitro with lipopolysaccharide (LPS) produce a high resolution, lipid-dominated spectrum on 1H-NMR spectroscopy (May et al, 1993. J. Infect. Dis. 168: 386-392). We have investigated the origin of this lipid signal using NMR and chemical analyses of both whole neutrophils and purified plasma membranes. Plasma membranes from neutrophils that had been stimulated with 50 microg/ml LPS exhibited the high resolution 1H-NMR signal, and contained double the triacylglycerol (TAG) content of plasma membranes isolated from resting cells. Chemical analysis of the whole cells indicated that the TAG also increased at the cellular level (1.7-fold) after stimulation with LPS. Diradylglycerol increased 2- to 3-fold in both whole cells and plasma membranes after stimulation, but was only a minor component compared with TAG. The plasma membrane protein/phospholipid ratio increased 2.6-fold, whereas cholesterol (free and esterified) was unchanged. The membranes from LPS-stimulated neutrophils exhibited increased fluidity, as judged by increased merocyanine 540 binding, consistent with a 2-fold reduction in cholesterol/phospholipid ratio. LPS induced a shift in fatty acid content of whole cell polar lipids towards more oleic acid and less palmitic acid, whereas the neutral lipid fraction contained increased amounts of palmitic and stearic acids. The TAG fraction of plasma membrane lipids contained increased amounts of palmitic acid when prepared from cells stimulated with LPS. We conclude that the 1H-NMR signal in LPS-stimulated neutrophils arises from increased amounts of plasma membrane TAG with an elevated content of palmitic acid.

Cell Membrane↗