Statins and the prevention of dementia.
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Biomedical subjects
Publications and source records attributed to U N Das.
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Previous studies showed that essential fatty-acid deficiency, conjugated linoleic acid, and a peroxisome proliferator-activated receptor-gamma binding agent such as troglitazone can prevent the development of diabetes mellitus in experimental animals. In the present study, we observed that oral supplementation with oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid could protect the animals against alloxan-induced diabetes mellitus. These oils rich in omega-3 and omega-6 fatty acids not only significantly attenuated chemical-induced diabetes mellitus but also restored the antioxidant status to normal range. Changes in the concentrations of different fatty acids shown by the phospholipid fractions of plasma, liver, and muscle tissues that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in these animals. Based on these results and the known mechanisms of alloxan, we suggest that omega-3 and omega-6 long-chain fatty acids can prevent chemically induced diabetes mellitus by enhancing the antioxidant status and suppressing production of cytokines.
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Endothelial cells produce vasodilator and vasoconstrictor substances. Dietary factors such as sodium, potassium, calcium, magnesium, zinc, selenium, vitamins A, C, and E, and essential fatty acids and their products such as eicosanoids can influence blood pressure, cardio- and cerebrovascular diseases, and concentrations of blood lipids and atherosclerosis. There might be a close interaction between these dietary factors, sympathetic and parasympathetic nervous systems, the metabolism of essential fatty acids, nitric oxide, prostacyclin, and endothelium in human essential hypertension. A deficiency in any one factor, dietary or endogenous, or alterations in their interactions with each other, can lead to endothelial dysfunction and development of hypertension. Therefore, alterations in the metabolism of essential fatty acids might be a predisposing factor to the development of essential hypertension and insulin resistance.
I suggest that insulin suppresses the secretion and antagonizes the harmful effects of tumor necrosis factor-alpha, macrophage migration-inhibitory factor, and superoxide anion. Therefore, the glucose-insulin-potassium regimen might be beneficial in acute myocardial infarction and useful in the management of patients with septicemia, septic shock, and other inflammatory diseases in which tumor necrosis factor-alpha and macrophage migration-inhibitory factor have important roles.
Insulin seems to have the ability to suppress the production of tumor necrosis factor-alpha and superoxide anion, enhance the synthesis of nitric oxide and inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) through stimulation of nitric oxide. This suggests that insulin can behave as an anti-inflammatory molecule. In view of this, it is suggested that insulin in combination with glucose and potassium may be of benefit in the management of inflammatory bowel disease.
Previous studies showed that essential fatty acid (EFA) deficiency, conjugated linoleic acid and troglitazone exert a protective effect in animal models of diabetes mellitus. Here we show that alloxan-induced in vitro cytotoxicity and apoptosis in an insulin secreting rat insulinoma, RIN, cells can be prevented by arachidonic acid (AA) and that both cyclo-oxygenase and lipoxygenase inhibitors do not block this protective action. Alloxan-induced diabetes in male Wistar rats was also prevented by oral supplementation of AA, gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This protective action is best when the animals were pre-treated with the fatty acid. These results suggest that polyunsaturated fatty acids can prevent alloxan-induced diabetes mellitus in experimental animals and may be useful to prevent diabetes mellitus in the high-risk population.
Vegetarians are known to have a low incidence of cardiovascular diseases and lower blood pressure compared to non-vegetarians. The exact cause for this is not known. In the present study, it was found that, in general, vegetarians (female > males) have a higher concentrations of anti-oxidant enzymes: catalase and superoxide dismutase in their RBC membranes and lower levels of plasma lipid peroxides compared to non-vegetarians. Both male and female non-vegetarians were found to have a higher n-3/n-6 ratio compared to vegetarians. These results suggest that vegetarians have a higher anti-oxidant status and low levels of n-3 fatty acids. It remains to be seen whether this alterations in the oxidant and anti-oxidant status and n-3 concentrations explains the lower incidence of cardiovascular diseases and lower blood pressure in vegetarians.
Statins and polyunsaturated fatty acids have similar actions: both enhance endothelial nitric oxide synthesis, inhibit the production of pro-inflammatory cytokines, lower cholesterol levels, prevent atherosclerosis and are of benefit in coronary heart disease, stroke and osteoporosis. Statins enhance the conversion of linoleic acid and eicosapentaenoic acid to their long chain derivatives. Animals with essential fatty acid deficiency show an increase in HMG-CoA reductase activity, which reverts to normalcy following topical application of linoleic acid. Similarly to statins, polyunsaturated fatty acids also inhibit HMG-CoA reductase activity. In view of the similarity in their actions and as statins influence essential fatty acid metabolism, it is suggested that essential fatty acids and their metabolites may serve as second messengers of the actions of statins.
In systemic lupus erythematosus, plasma concentrations of tumor necrosis factor alpha (TNF alpha) and other pro-inflammatory cytokines are elevated and those of transforming growth factor beta (TGF beta) are decreased. TNF alpha prevents lupus nephropathy whereas increased concentration of TGF beta causes glomerulosclerosis. Insulin inhibits TNF alpha and enhances TGF beta production, augments nitric oxide synthesis and blocks superoxide anion generation. Polyunsaturated fatty acids (PUFAs) also have actions similar to insulin. Hence, it is suggested that a combination of insulin (in the form of glucose-insulin-potassium) and PUFAs may be of benefit in lupus and other inflammatory conditions.
It is known that the concentrations of essential fatty acids and their metabolites including eicosanoids, free radicals and anti-oxidants are altered in glomerular disorders. Both corticosteroids and n-3 fatty acids--eicosapentaenoic acid and docosahexaenoic acid (EPA and DHA respectively)--are useful in the management of glomerular disorders. In the present study, the altered plasma concentrations of lipid peroxides, nitric oxide and the metabolites of essential fatty acids and anti-oxidants--superoxide dismutase, glutathione peroxidase and vitamin E--in the RBC membranes of patients with glomerular disorders (nephrotic syndrome) reverted to normalcy following corticosteroids or EPA/DHA administration. This suggests that the beneficial actions of corticosteroids and EPA/DHA in glomerular disorders can be attributed to their action on the pro-oxidant and anti-oxidant concentrations and metabolism of essential fatty acids.
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It is suggested that adequate provision of long-chain polyunsaturated fatty acids during the critical periods of brain growth prevents the development of hypertension in later life.
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Recent advances suggest that toll-like receptors, various cytokines, cicosanoids, free radicals and macrophage migration inhibitory factor (MIF) play an important role in the pathobiology of septicemia and septic shock. Anti-MIF antibodies can decrease the plasma concentrations of tumor necrosis factor (TNF), lower bacterial circulating counts and enhance survival of animals with septicemia and septic shock. Monocyte expression of MHC-class II antigens, neutrophil expression of the integrin CD11b/CD18 and neutrophil activation can be related to the development of, and/or recovery from, post-operative sepsis. Thus, biological variations in the response of an individual to a given stimulus, appears to determine his/her ability or inability to develop and also recover from sepsis and septic shock. This suggests that it may be possible to predict the development of septicemia and septic shock in a given individual and take appropriate action both to prevent and treat them adequately.
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