Phospholipids block nuclear factor-kappa B and tau phosphorylation and inhibit amyloid-beta secretion in human neuroblastoma cells.

Inflammation and oxidative stress have been shown to play a critical role in the pathophysiology that leads to neurodegeneration. Omega-6 phospholipids, e.g. dilinoleoylphosphatidylcholine (DLPC), have been shown to have anti-inflammatory properties and therefore experiments were undertaken to determine whether DLPC can prevent inflammatory neurodegenerative events in the model neuronal cell line, SH-SY5Y. Tumor necrosis factor (TNF-alpha) and H(2)O(2) activate mitogen-activated protein kinase (MAPK) in SH-SY5Y cells within 5 min and this activation is completely blocked by DLPC (12 microM). DLPC blocks IkappaBalpha phosphorylation in the SH-SY5Y cells and prevents the phosphorylation and activation of nuclear factor-kappa B (NF-kappaB). The phospholipid inhibits induction of MAPK and NF-kappaB in similar fashion to the MEK1/2-inhibitor, U0126 (10 microM). DLPC completely abolishes TNF-alpha, H(2)O(2) and lipopolysaccaride (LPS)-induced neuronal tau phosphorylation. Cellular amyloid precursor protein levels are reduced by DLPC and LPS-induced amyloid-beta expression and secretion in SH-SY5Y cells are completely blocked by DLPC. Taken together, these data suggest that DLPC can act through MAPK to block neuronal inflammatory cascades and prevent potential pathological consequences in the neuronal metabolism of amyloid and tau proteins.

Enzymatic oxidant and antioxidants of human blood platelets in unstable angina and myocardial infarction.

In ischaemic heart conditions we report a remarkable increase in platelet xanthine oxidase activity and rise in the levels of malondialdehyde (MDA) with concomitant decrease in the activities of free radical scavenging enzymes - superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. The increased levels of free radical generating system and MDA and lowered levels of free radical scavenging systems seem to have critical role in ischaemic heart conditions.

Oxidant stress mechanisms in heart failure.

Evidences clearly indicate that HF is accompanied by excessive generation of OFRs and depletion of endogenous antioxidant system. The resultant oxidant stress depresses myocardial contractility and function by decreasing Ca++ uptake in sarcoplasmic reticulum and by impaired Ca(++)-ATPase in cardiac tissue. The various sources of OFRs production in HF include increased production of nitric oxide, cytokines, prostaglandins, auto-oxidation of catecholamines, activation of polymorph leucocytes and ischemia induced xanthine-xanthine oxidase. The prevention of oxidative stress by antioxidant translates into better metabolism and function of myocytes. It appears that antioxidant drugs may represent a novel adjunct to the existing therapeutic armamentarium in patients of HF irrespective of its etiology and severity.

Lipid peroxidation in human blood platelets during unstable angina and myocardial infarction.

A comparative study on the levels of lipid peroxidation in human platelets has been undertaken in patients of unstable angina and reperfused acute myocardial infarction and matched healthy individuals. Lipid peroxidation increases in these patients, most marked increase were in the patients of reperfused myocardial infarction.