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Biomedical subjects

U N Das

Publications and source records attributed to U N Das.

At least 55 records · Page 3Linked to original sources
PubMed2000

Oxidant stress, antioxidants and nitric oxide in traffic police of Hyderabad, India.

Exposure to environmental pollutants is known to be harmful to health, in general, and to lungs in particular. In this respect, traffic police are at particular risk due to the nature of their job, since they are exposed to emissions from the vehicles. Here, we show that in the traffic police of Hyderabad city, India, the plasma levels of lipid peroxides are high, whereas the concentrations of the nitric oxide are low. In addition, the levels of various antioxidants in the RBC lysate such as catalase, superoxide dismutase and glutathione peroxidase were found to be low with no significant alteration in plasma ceruloplasmin levels. These results suggest that exposure to air pollutants, a major portion of which is due to emissions from the vehicles, can increase oxidant stress, decrease the levels of antioxidants and nitric oxide. This imbalance in the oxidant/antioxidant system may lead to lung damage and is likely to cause respiratory problems in individuals exposed to air pollution.

Journal Article↗
PubMed2000

Free radicals, cytokines and nitric oxide in cardiac failure and myocardial infarction.

Myocardial infarction is the most common cause of congestive cardiac failure. Free radicals, cytokines, nitric oxide (NO) and antioxidants play a major role both in atherosclerosis and myocardial damage and preservation. In the early stages of atherosclerosis, neutrophils and monocytes infiltrate the intima and generate free radicals which damage the endothelial cells. As a result, production of NO and prostacyclin by the endothelial cells declines, which have cardioprotective actions. This also has relevance to the beneficial action of aspirin since, it can modulate both prostanoid and L-arginine-NO systems and NF-kB translocation. In both acute myocardial infarction and chronic congestive cardiac failure, the plasma levels of various inflammatory mediators such as interleukins and tumour necrosis factor-alpha (TNFalpha) are elevated. TNFalpha, produced by the inflammatory cells and the myocardium, can suppress myocardial contractility and induce the production of free radicals, which in turn can further damage the myocardium. Transforming growth factor beta (TGFbeta), polyunsaturated fatty acids and the glucose-insulin-potassium regimen can antagonize the harmful actions of TNFalpha and protect the myocardium. This explains why efforts made to reduce the levels of pro-inflammatory cytokines have beneficial action and preserve the myocardium.

Animals↗
PubMed2000

Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus.

Several studies have shown that the activities of delta-6-desaturase and delta-5-desaturase are depressed in experimental diabetes and in humans with insulin- and non-insulin-dependent diabetes mellitus (type I and type II diabetes mellitus respectively). Furthermore, treatment with insulin is known to correct the defects in desaturases in rats and humans with diabetes, especially in type I. In a recent study, we demonstrated that L-arginine and nitric oxide can prevent alloxan-induced beta cell damage, and the severity of diabetes, and restore the antioxidant status to near normal levels. But, no information is available as to the relationship between L-arginine-nitric oxide system and the metabolism of essential fatty acids in diabetes mellitus. In the present study, it was noted that the plasma levels of saturated fatty acids: stearic and palmitic were increased where as unsaturated fatty acids such as oleic, linoleic, gamma-linolenic and eicosapentaenoic acids (OA, LA, GLA and EPA respectively) were decreased in alloxan-induced diabetic rats. In the liver phospholipid (PL) fraction, GLA, DGLA (dihomo-GLA) and alpha-linolenic acid (ALA) were decreased in the alloxan-treated group; in the muscle PL fraction, LA, GLA and DGLA were low, whereas an increase in the saturated fatty acid content was noted. L-arginine (the precursor of nitric oxide) and sodium nitroprusside (a nitric oxide donor) treatment of alloxan-induced diabetic rats enhanced the levels of LA, GLA and DGLA. Further, nitric oxide synthase inhibitor, L-NMMA, prevented this beneficial action of L-arginine-nitric oxide system on essential fatty acid metabolism. The abnormalities in the essential fatty acid metabolism observed also reverted to normalcy following control of diabetes with insulin. These results indicate that nitric oxide can enhance the activities of delta-6- and delta-5 desaturases, which are depressed in diabetes, and suggests that there is a close interaction between L-arginine-nitric oxide system and the metabolism of essential fatty acids.

8,11,14-Eicosatrienoic Acid↗
PubMed2000

Effect of polyunsaturated fatty acids on dexamethasone-induced gastric mucosal damage.

BACKGROUND: Increased dietary intake of polyunsaturated fatty acids (PUFAs) is known to be associated with a decrease in the incidence of peptic ulcer disease possibly due to increase in the synthesis of prostaglandins. But, it is also likely that conversion of PUFAs to PGs may not always be required for gastric mucosal protection. Present study was designed to study the role of PUFAs in pathobiology of steroid induce gastric damage in rats. METHODS: Wistar rats were treated with 5 mg/kg bodyweight of dexamethasone to induce gastric mucosal ulcers. Effects of PUFAs was studied by supplementation of Fish oil (rich in n-3 EPA and DHA) and AA rich oil. Famotidine was used as a positive control. Generation of lipid peroxides, nitric oxide and the activity of anti-oxidant enzymes were also studied. RESULTS: Dexamethasone induced ulceration was associated with changes in the phospholipid fatty acid profile, levels of lipid peroxidation products, nitric oxide and activity of anti-oxidant enzymes. The fatty acid profile showed an increase in LA and a decrease in other PUFAs like GLA, AA, EPA and DHA. When PUFAs were supplemented in the form of Fish oil and AA rich oil or when the animals were treated with H2-blocker, famotidine, there was a decrease in the incidence of ulceration in the animals associated with near normalization of changes in the phospholipid fatty acid profile. The levels of lipid peroxides, nitric oxide, and anti-oxidant activity also reverted to control values. CONCLUSIONS: Dexamethasone induced gastric ulceration was prevented by PUFAs. This is supported by the results of our earlier study where in it was noted that in patients with DU plasma lipid peroxides, nitric oxide and phospholipid fatty acid pattern and red cell antioxidant activity were altered similar to those seen in dexamethasone treated group of the present study. These abnormalities, similar to the PUFA treated groups of the present study, reverted to normalcy following treatment of the patients with lansoprazole, a proton pump inhibitor. Further, PUFAs are known to inhibit the growth of Helicobacter pylori in vitro. Hence, it is concluded that PUFAs, free radicals, nitric oxide and anti-oxidants play a significant role in the pathobiology of peptic ulcer.

Animals↗
PubMed2000

Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.

Acetylcholine↗
PubMed1999

GLUT-4, tumor necrosis factor, essential fatty acids and daf-genes and their role in insulin resistance and non-insulin dependent diabetes mellitus.

It is now believed that the GLUT-4 receptor, tumor necrosis factor-alpha (TNF-alpha), essential fatty acids (EFAs) and their metabolites and daf-genes have an important role in the development of obesity and non-insulin dependent diabetes mellitus (NIDDM). The protein encoded by daf-2 is 35% identical to the human insulin receptor, daf-7 codes a transforming growth factor-beta (TGF-beta) type signal and daf-16 can enhance superoxide dismutase (SOD) expression. EFAs and their metabolites can alter the cell membrane fluidity and enhance the expression of GLUT-4 and insulin receptors. EFAs can suppress TNF-alpha production and secretion, a mechanism that may have relevance to the role of these fatty acids in the pathogenesis of insulin resistance, obesity and NIDDM. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Based on this evidence, it is proposed that GLUT-4, TNF-alpha, EFAs, daf-genes, melatonin and leptin interact with each other in ways which may have relevance to the development or abrogation of insulin resistance, obesity, NIDDM, complications due to NIDDM, longevity and ageing.

Caenorhabditis elegans Proteins↗
PubMed1999

Effect of cis-unsaturated fatty acids on the activity of protein kinases and protein phosphorylation in macrophage tumor (AK-5) cells in vitro.

Cis-unsaturated fatty acids (c-UFAs) have been shown to be capable of decreasing the survival of macrophage tumor (AK-5) cells in vitro. This cytotoxic action of c-UFAs was found to be associated with an increase in free radical generation and lipid peroxidation process and a simultaneous decrease in cellular anti-oxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, glutathione and vitamin E. In the present study, it was observed that c-UFAs such as gamma linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can activate phospholipase C (PLC) and enhance diacylglycerol formation; all the fatty acids except alpha linolenic acid (ALA) increased the binding of phorbol dibutyrate acetate (PDBu) suggesting translocation of protein kinase C (PKC) and at the same time these fatty acids (especially GLA, AA, EPA and DHA) also enhanced PKC activity. AA, EPA and DHA decreased the activity of protein kinase A (PKA) both in the cytosol and particulate fractions whereas ALA and GLA enhanced the PKA activity in the particulate fractions; all the fatty acids except ALA reduced cyclic AMP levels and an enhanced phosphorylation of about 13 proteins of the nuclear fraction and about eight proteins of the plasma membrane fraction was noted in c-UFA treated AK-5 cells in vitro. These results suggest that c-UFAs can alter the activities of second messenger systems such as diacylglycerol and protein kinases and can phosphorylate both plasma membrane and nuclear proteins which are likely to be components of NADPH oxidase. Based on these results, it is suggested that fatty acids may mediate their cytotoxic action in part by modulating the expression of PKC. Activated PKC may then intensify the pro-oxidant state by augmenting NADPH oxidase, so inducing superoxide anion generation which may ultimately lead to cytolysis.

Animals↗
PubMed1999

Essential fatty acids, lipid peroxidation and apoptosis.

Essential fatty acids (EFAs) and their metabolites, especially gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid and decosahexaenoic acid are known to induce apoptotic death of tumour cells. But the exact mechanism by which these fatty acids are able to induce apoptosis is not clear. Recent studies suggest that these fatty acids are able to induce apoptosis in cells over expressing cytochrome P450 following depletion of cellular glutathione and inhibition of carnitine palmitoyl transferase I (CPTI) activity. On the other hand, BCL-2 prevented apoptosis induced by these long-chain fatty acids, where as n-3 fatty acids suppressed ras expression leading to suppression of development of overt neoplasia. Phosphorylation of BCL-2 inhibits its ability to interfere with apoptosis and enhances lipid peroxidation leading to the occurrence of apoptosis. Tumour cells treated with long-chain fatty acids show increase in lipid peroxidation process, depletion of antioxidants and phosphorylation of proteins. Based on these results, it is suggested that long-chain fatty acids induce apoptosis by enhancing lipid peroxidation, suppressing BCL-2 expression possibly by phosphorylation and augmentation of P450 activity. Thus, these long-chain fatty acids may, infact act at the level of gene/oncogene expression in producing their cytotoxic action on tumour cells.

Animals↗
PubMed1999

Lipid peroxides, nitric oxide and essential fatty acids in patients with Plasmodium falciparum malaria.

Long chain polyunsaturated fatty acids derived from essential fatty acids have been shown to be toxic to Plasmodium falciparum both in vitro and in vivo. Here, we present evidence to suggest that in patients with Plasmodium falciparum malaria the levels of lipid peroxides (a marker of free radical generation) nitric oxide (a potent free radical with immunomodulatory actions), and concentrations of linoleic acid (LA) and alpha-linolenic acid (ALA) are low, whereas those of eicosapentaenoic acid (EPA) are high. The ability of the fatty acids to kill P. falciparum is dependent on their capacity to stimulate free radical generation in neutrophils and macrophages. EPA is more potent than LA in killing the parasite. In view of this, the results of the present study suggest that in patients with P. falciparum malaria the decreased levels of lipid peroxides and nitric oxide may contribute to the persistence of the infection, whereas elevated levels of EPA may be a feeble attempt to overcome this defect.

Animals↗
PubMed1999

GLUT-4, tumour necrosis factor, essential fatty acids and daf-genes and their role in glucose homeostasis, insulin resistance, non-insulin dependent diabetes mellitus, and longevity.

GLUT-4 receptor, tumor necrosis factor-alpha (TNF-alpha), essential fatty acids (EFAs) and their metabolites and daf-genes seem to play an important and essential role in the maintenance of glucose homeostasis, and in the pathobiology of obesity and non-insulin dependent diabetes mellitus (NIDDM). Daf-genes encode for proteins which are 35% identical to the human insulin receptor, a transforming growth factor-beta (TGF-beta) type signal and can also enhance the expression of superoxide dismutase (SOD). On the other hand, EFAs and their metabolites can increase the cell membrane fluidity and thus, enhance the expression of GLUT-4 and insulin receptors. In addition, EFAs can suppress TNF-alpha production and secretion and thus, are capable of reversing insulin resistance. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Hence, it is likely that there is a close interaction between GLUT-4, TNF-alpha, EFAs, daf-genes, melatonin and leptin that may have relevance to the development of insulin resistance, obesity, NIDDM, complications due to NIDDM, longevity and ageing.

Diabetes Mellitus, Type 2↗
PubMed1999

Essential fatty acids in health and disease.

Essential fatty acids (EFAs) form an important component of cell membranes, are eicosanoid precursors and are therefore required for both the structure and function of every cell in the body. EFAs can modulate the activity of protein kinase C, T and B cell response, free radical generation and lipid peroxidation, lymphokine secretion and cell proliferation. EFAs also have anti-mutagenic, anti-bacterial, anti-fungal and anti-viral properties. EFAs and their metabolites lower serum cholesterol, triglycerides and blood pressure. EFAs appear to be of benefit in atopic eczema, premenstrual syndrome, psoriasis, auto-immune disorders especially rheumatoid arthritis and systemic lupus erythematosus, prevention of target organ damage in diabetes mellitus, peptic ulcer disease, ulcerative colitis, coronary heart disease and atherosclerosis. EFAs and their metabolites can selectively kill tumor cells both in vitro and in vivo without harming normal cells. In addition, EFAs seem to play a fundamental role in inflammation and immune response. In view of their actions and relative safety, it is anticipated that EFAs may be useful in the management of several diseases.

Cell Membrane↗
PubMed1998

Effect of L-arginine-nitric oxide system on chemical-induced diabetes mellitus.

Several in vitro studies have suggested that nitric oxide may be the mediator of cytokine-induced beta-cell destruction. On the other hand, in vivo studies have given conflicting results: some studies suggesting that nitric oxide synthase inhibitors do not suppress streptozotocin-induced diabetes in mice, while others revealed that nitric oxide synthase inhibitors can reduce the incidence of insulin-dependent diabetes mellitus in rats. The results of the present study indicate that alloxan-induced diabetes in the male Wistar rats can be abrogated to a large extent by prior and simultaneous administration of the precursor of nitric oxide, L-arginine, where as NG-monomethy-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase, can completely block the beneficial action of L-arginine. Sodium nitroprusside, a nitric oxide donor, also showed significant inhibitory effect on the severity of diabetes induced by alloxan. Alloxan treatment reduced nitric oxide generation, whereas L-arginine and sodium nitroprusside, when given along with alloxan, enhanced nitric oxide production to control values. Induction of diabetes by alloxan in the experimental animals was associated with a marked elevation in plasma lactate, ketone body, and lipid peroxide levels with a simultaneous fall in plasma insulin and nitric oxide levels. Alloxan-induced diabetes also induced a fall in the levels of anti-oxidant enzymes such as superoxide dismutase, glutathione reductase, and total glutathione, and antioxidants: vitamin E and ceruloplasmin, and an increase in glutathione peroxidase and glutathione-S-transferase. All these biochemical abnormalities and antioxidant levels have improved to near normal levels in animals treated with insulin, L-arginine, and sodium nitroprusside. From the results of the present study, it is apparent that L-arginine and nitric oxide can prevent alloxan-induced beta-cell damage, and the development of diabetes, and restore the antioxidant status to near normal levels.

Alloxan↗
PubMed1998

Effect of cis-unsaturated fatty acids on Meth-A ascitic tumour cells in vitro and in vivo.

Earlier studies performed both by us and by others have demonstrated that some n-3 and n-6 fatty acids can inhibit the growth of tumour cells in vitro. Though studies done with various types of oils rich in n-3 and n-6 fatty acids did show that the tumour incidence and growth can be modified, there were relatively few studies wherein the anti-tumour effects of individual free fatty acids were studied. Here we present results which suggest that free fatty acids (oleic acid (OA), linoleic acid (LA), alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) can inhibit the growth of methylcholanthrene-induced sarcoma cells (Meth-A cells) in vitro. The order of potency of various fatty acids on the growth of Meth-A cells was DHA > ALA > EPA > AA > GLA > LA > OA and their ID50 values were 10, 20, 35, 45, 68, 73 and 110 microg/ml/1 x 10(4) cells, respectively. These results indicate that the inhibitory action of different types of n-3, n-6 and n-9 fatty acids on Meth-A cells does not depend on their unsaturation. Vitamin E could partially block the cytotoxicity of these fatty acids indicating a possible role for free radicals. GLA, AA and EPA augmented the generation of superoxide anion and lipid peroxidation in Meth-A cells indicating a possible correlation between the ability of fatty acids to augment free radicals and their tumoricidal action. In an in vivo study, it was observed that OA, LA, ALA, GLA and EPA can prolong the survival of Meth-A-bearing mice when given intraperitoneally. Of all the fatty acids tested, surprisingly, LA was found to be the most potent in enhancing the survival of the tumour-bearing animals at all the concentrations tested. Thus, these studies suggest that free fatty acids can inhibit Meth-A tumour cell proliferation both in vitro and in vivo.

Animals↗
PubMed1998

Effect of evening primrose and fish oils on two stage skin carcinogenesis in mice.

The effect of fish oil (FO, given in the form of MaxEPA) rich in n-3 fatty acids and evening primrose oil (EPO) rich in n-6 fatty acids on two-stage skin carcinogenesis in mice was studied. Both FO and EPO inhibited the papilloma formation to a significant degree only during the promotion stage which was associated with an increase in lipid peroxidation. Both FO and EPO inhibited the binding of benzo(a)-pyrene to skin cell DNA suggesting that this could be one of the mechanism(s) by which these oils could be preventing papilloma development. Neither EPO nor FO influenced epidermal cell proliferation. In the FO group, LA (linoleic acid), AA (arachidonic acid) and DHA (docosahexaenoic acid) were increased, whereas in the EPO group a significant increase in the AA content was noted. No specific changes in the fatty acid pattern were observed in any of the groups that could be attributed to the papilloma incidence. These results suggest that FO and EPO can influence papilloma formation which can be attributed, at least in part, to their ability to prevent benzo(a)pyrene binding to DNA and to an increase the lipid peroxidation process.

Animals↗