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Biomedical subjects

Undurti N Das

Publications and source records attributed to Undurti N Das.

At least 19 recordsLinked to original sources
PubMed2006

Is pyruvate an endogenous anti-inflammatory molecule?

Pyruvic acid is an effective scavenger of reactive oxygen species. Ethyl pyruvate has demonstrated anti-inflammatory actions and improved hyperpermeability and bacterial translocation due to endotoxemia and is of benefit in animal models of sepsis and septic shock. Ethyl pyruvate specifically inhibits tumor necrosis factor-alpha production and decreases circulating levels of high-mobility group box-1 and nuclear factor-kappaB signaling pathways by specifically targeting its p65 subunit in animals with established endotoxemia or sepsis and in macrophage cultures. Ethyl pyruvate also decreases cyclo-oxygenase-2, inducible nitric oxide synthase, and interleukin-6 mRNA expression in the liver, ileal mucosa, and colonic mucosa in animal models with hemorrhagic shock. Similar beneficial actions have been seen in endotoxemia. These and other studies suggest that ethyl pyruvate could be of significant benefit in the treatment of patients who are critically ill and have sepsis/septic shock.

Animals↗
PubMed2006

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent atopy, bronchial asthma and other inflammatory conditions?

I suggest that perinatal supplementation of long-chain polyunsaturated fatty acids (LCPUFAs) protects against the development of childhood and adult life eczema, atopy, bronchial asthma and other inflammatory conditions. LCPUFAs modulate T(H)1 and T(H)2 cell generation and their cytokine production such that the balance is tilted more towards the production of anti-inflammatory cytokines. In addition, LCPUFAs form precursors to anti-inflammatory products such as resolvins, lipoxins, and aspirin-triggered 15 epimer LXs (ATLs), nitric oxide, prostaglandin E1 and prostacyclin (PGI2) that suppress inflammatory process and enhance healing of tissue injury with little or no loss of function. These beneficial actions of LCPUFAs explain the protective effect of exclusive breast-feeding against eczema and other childhood allergies, and decreased incidence of several other inflammatory conditions in adult life since human breast milk contains substantial amounts of these long-chain polyunsaturated fatty acids.

Asthma↗
PubMed2006

Effect of gamma-linolenic acid and prostaglandins E1 on gamma-radiation and chemical-induced genetic damage to the bone marrow cells of mice.

The effect of gamma-linolenic acid (GLA) and prostaglandin E1 (PGE1) on gamma-radiation, diphenylhydantoin (DPH), benzo(a)pyrene (BP), and 4-alpha-phorbol-induced genetic damage to the bone marrow cells of mice, using the sensitive micronucleus (MN) test was investigated. PGE1 and its precursor GLA prevented gamma-radiation, DPH, BP, and 4-alpha-phorbol-induced genetic damage.

Alprostadil↗
PubMed2006

Differential effect of saturated, monounsaturated, and polyunsaturated fatty acids on alloxan-induced diabetes mellitus.

Earlier, we reported that oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid prevented the development of alloxan-induced diabetes mellitus in experimental animals. Here we report the results of our studies with pure saturated stearic acid (SA), monounsaturated oleic acid (OA) and omega-6 arachidonic acid (AA) on alloxan-induced diabetes mellitus in Wistar male rats. Prior oral supplementation with AA prevented alloxan-induced diabetes mellitus, whereas both SA and OA were ineffective. Cyclo-oxygenase (COX) and lipoxygenase (LO) inhibitors did not block this protective action of AA against alloxan-induced diabetes, suggesting that both prostaglandins and leukotrienes are not involved, and that AA by itself is effective. Furthermore, AA restored the anti-oxidant status to normal range in various tissues. These results suggest that AA protects pancreatic beta cells against alloxan-induced diabetes in experimental animals by attenuating oxidant stress.

Alloxan↗
PubMed2006

Essential fatty acids: biochemistry, physiology and pathology.

Essential fatty acids (EFAs), linoleic acid (LA), and alpha-linolenic acid (ALA) are essential for humans, and are freely available in the diet. Hence, EFA deficiency is extremely rare in humans. To derive the full benefits of EFAs, they need to be metabolized to their respective long-chain metabolites, i.e., dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites not only form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), but also give rise to lipoxins (LXs) and resolvins that have potent anti-inflammatory actions. Furthermore, EFAs and their metabolites may function as endogenous angiotensin-converting enzyme and 3-hdroxy-3-methylglutaryl coenzyme A reductase inhibitors, nitric oxide (NO) enhancers, anti-hypertensives, and anti-atherosclerotic molecules. Recent studies revealed that EFAs react with NO to yield respective nitroalkene derivatives that exert cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors. The metabolism of EFAs is altered in several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer. Thus, EFAs and their derivatives have varied biological actions and seem to be involved in several physiological and pathological processes.

Animals↗
PubMed2006

Essential Fatty acids - a review.

Essential fatty acids (EFAs): cis-linoleic acid (LA) and alpha-linolenic acid (ALA) are essential for humans and their deficiency is rare in humans due to their easy availability in diet. EFAs are metabolized to their respective long-chain metabolites: dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), lipoxins (LXs) and resolvins. EFAs and their metabolites may function as endogenous angiotensin converting enzyme and HMG-CoA reductase inhibitors, nitric oxide enhancers, anti-hypertensives, and anti-atherosclerotic molecules. EFAs react with nitric oxide (NO) to yield respective nitroalkene derivatives that have cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). In several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, alcoholism, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer the metabolism of EFAs is altered. Thus, EFAs and their derivatives have significant clinical implications.

Animals↗
PubMed2006

Tumoricidal and anti-angiogenic actions of gamma-linolenic acid and its derivatives.

Studies showed that gamma-linolenic acid (GLA) and its derivatives have the potential to be anti-cancer molecules. In vitro, in vivo and limited clinical studies showed that GLA has selective tumoricidal action with little or no side effects. The mechanism of its action appears to be by inducing apoptosis of tumor cells by augmenting free radical generation only in the tumor cells but not normal cells. Intra-arterial injection of a lithium salt derivative of GLA demonstrated its ability to selectively occlude tumor-feeding vessels. Since GLA is an endogenous naturally occurring molecule and has no significant side effects, it calls for more studies to exploit its potential as a novel anti-cancer drug.

Animals↗
PubMed2006

Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule.

Pyruvic acid, an intermediate metabolite of glucose, an effective scavenger of reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production and NF-kappaB signaling pathways, reduces circulating levels of HMGB1 (high mobility group B1), decreases COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa, and colonic mucosa in animal models with endotoxemia. These studies suggest that pyruvate has potent anti-oxidant and anti-inflammatory actions. Insulin influences the production of pyruvate by its action on glucose metabolism and pyruvate is an insulin secretagogue. This suggests that in metabolic syndrome X, obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is common due to enhanced TNF-alpha production) pyruvate plays a role. This may have relevance to the use of glucose-insulin-potassium regimen in these clinical conditions, sepsis, and cancer.

Animals↗
PubMed2005

Fish consumption among healthy adults is associated with decreased levels of inflammatory markers related to cardiovascular disease: the ATTICA study.

OBJECTIVES: The aim of this work was to investigate the association between fish consumption and levels of various inflammatory markers among adults without any evidence of cardiovascular disease. BACKGROUND: Fish consumption has been associated with reduced risk of coronary heart disease, but the mechanisms have not been well understood or appreciated. METHODS: The ATTICA study is a cross-sectional survey that enrolled 1,514 men (age 18 to 87 years) and 1,528 women (age 18 to 89 years) from the Attica region, Greece. Of them, 5% of men and 3% of women were excluded due to a history of cardiovascular disease. Among others, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, serum amyloid A (SAA), and white blood cells (WBC) were measured, and dietary habits (including fish consumption) were evaluated using a validated food frequency questionnaire. RESULTS: A total of 88% of men and 91% of women reported fish consumption at least once a month. Compared to non-fish consumers, those who consumed >300 g of fish per week had on average 33% lower CRP, 33% lower IL-6, 21% lower TNF-alpha, 28% lower SAA levels, and 4% lower WBC counts (all p < 0.05). Significant results were also observed when lower quantities (150 to 300 g/week) of fish were consumed. All associations remained significant after various adjustments were made. CONCLUSIONS: Fish consumption was independently associated with lower inflammatory markers levels, among healthy adults. The strength and consistency of this finding has implications for public health and should be explored further.

Adult↗
PubMed2005

COX-2 inhibitors and metabolism of essential fatty acids.

Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke that is attributed to their ability to inhibit prostacyclin (PGI2), lipoxins, resolvins, and endothelial nitric oxide (eNO) but not platelet COX-1 derived thromboxane A2 (TXA2). In contrast, aspirin blocks both COX-1 and COX-2 enzymes that, in turn, increases intracellular concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and reduced formation of eicosanoids. On the other hand, such an increase is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. DGLA, AA and EPA form precursors to PGE1, PGI2, and PGI3 respectively, which are potent vasodilators and platelet anti-aggregators, and thus aid in the prevention of thrombus formation. EPA has anti-arrhythmic action, and EPA, DHA (docosahexaenoic acid), DGLA, and PGE1 have anti-inflammatory actions as well. EPA, DHA, and AA augment eNO formation that has anti-atherosclerotic action. Hence, combining EFAs with COX-2 inhibitors will prevent thrombotic cardiovascular events.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Essential fatty acids and acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) that is characterized by profound immunodeficiency, opportunistic infections and Kaposi's sarcoma. As yet no effective therapy is available for AIDS, though retroviral drugs are able to prolong life and contain HIV proliferation to some extent. I propose that essential fatty acids (EFAs) and their metabolites could be useful in the prevention and management of AIDS. Linoleic acid (LA) and arachidonic acid (AA) inactivate enveloped viruses, linolenic acid-enriched macrophages are markedly tumoricidal, EFAs activate macrophages and neutrophils and induce free radical generation; and cytokines bring about some of their actions by inducing the release of EFAs; gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) prevent genetic damage and have tumoricidal actions as well; and are relatively non-toxic when administered orally or parentarally over long periods of time. In view of this, I suggest that further studies with regard to the role of GLA, AA, EPA and/or docosahexaenoic acid (DHA) in the pathobiology of AIDS needs to be performed. It is also proposed that possible use of these fatty acids in the prevention and treatment of AIDS needs serious consideration.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Is angiotensin-II an endogenous pro-inflammatory molecule?

Angiotensin-II, a product of angiotensin converting enzyme (ACE) action, regulates vascular tone, stimulates the release of pro-inflammatory cytokines, activates NFkappaB, increases oxidant stress, and suppresses nitric oxide synthesis. Thus, angiotensin-II is pro-inflammatory in nature. Hence, increase in ACE activity and the concentrations of angiotensin-II initiate and perpetuate inflammation. Since ACE is present in many tissues including: the uterus, placenta, vascular tissue, heart, brain, adrenal cortex and kidney, leukocytes, alveolar macrophages, peripheral monocytes, neuronal cells and epididymal cells, this suggests that angiotensin-II may have a role in atherosclerosis, congestive cardiac failure, stroke, bipolar disorder, schizophrenia, dementia, Alzheimer's disease, psoriasis, atopic and non-atopic dermatitis, eczema, several acute and chronic inflammatory diseases, and cancer, conditions in which inflammation is known to play a significant role. This suggests that ACE inhibitors and/or angiotensin-II receptor blockers could be of significant benefit in the management of these conditions. Alternatively, structural analogues of presently available ACE inhibitors and angiotensin-II receptor blockers could be developed such that they are not only useful in the treatment of hypertension and CHF but also possess anti-inflammatory actions.

Angiotensin II↗