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The role of sialic acid (SA) in the pathogenesis of atherosclerosis and as a predictor of cardiovascular events has attracted much attention in recent years. However, most studies investigating the role of total and lipid-bound sialic acids (TSA and LSA) in the pathogenesis of atherosclerosis lack information on the reason for the elevated SA concentrations in coronary heart disease and myocardial infarction. Since the inflammation-sensitive proteins are glycoproteins with SA residues, an increase in their levels due to some type of acute-phase reaction or inflammation could be responsible for the elevated TSA levels in acute myocardial infarction (AMI). Elevated serum SA levels might also be due to either shedding or secretion of free SA from the cell or cell membrane surface if neuraminidase levels are increased, or to the release of cellular SA-containing glycolipids and/or glycoproteins into plasma from myocardial cells after AMI. The aim of the present study was to investigate both the possible role of SA-rich inflammation-sensitive proteins and the cell damage due to elevated serum TSA levels in AMI. A possible role of serum LSA as an indicator of the shedding or secretion of SA from the cell or cell membrane surface in AMI was also evaluated. The study included 38 subjects with AMI and 32 healthy volunteers. Serum TSA and LSA were determined using the methods of Warren and Katopodis, respectively. The concentrations of serum SA-rich inflammation-sensitive proteins, namely alpha1-antitrypsin, alpha2-macroglobulin and ceruloplasmin were determined immunoturbidimetrically. Our data showed that: a) mean levels of serum TSA and LSA and SA-rich inflammation-sensitive proteins in patients with AMI were significantly increased; and b) there was a significant positive correlation between TSA and LSA and alpha1-antitrypsin in patients with AMI. Since the transfer of free SA to lipoproteins is required for an increase in serum LSA levels, and free SA for this transfer can be provided by the secretion of SA from the cell, it is obvious that the shedding or secretion of SA from the cell membrane surface or release of cellular SA from cells into the bloodstream due to cell damage after AMI also occur after AMI. As a result, we can report that either the shedding or secretion of SA from the cell or cell membrane surface and the increased output of SA-rich inflammation-sensitive proteins may together be responsible for the elevated TSA levels in AMI.

Although serum total sialic acid has been shown to be a cardiovascular risk factor, with elevated levels associated with increased cardiovascular mortality and also with cerebrovascular disease, the reason for the elevation in serum sialic acid content remains obscure. It has been shown that an increased output of serum proteins by the liver due to some type of acute phase reaction may be one of the possible sources of an increased serum sialic acid concentration in patients with myocardial infarction. An increase in the activity of sialidase, which cleaves the terminal sialic acid residues from oligosaccharides, glycoproteins and gangliosides, may also play an important role in the elevation of serum total sialic acid in myocardial infarction. Elevated serum total sialic acid in the blood might result either from the shedding or secreting of sialic acid from the cell membrane surface, or releasing of cellular sialic acid from the cell into the bloodstream due to cell damage after myocardial infarction. The purpose of the present study is to investigate serum total and lipid-bound sialic acid and the enzymes serum lactate dehydrogenase, creatine kinase and aspartate aminotransferase in patients with acute myocardial infarction, at 24 h post-infarction (day 1), 48 h post-infarction (day 2) and 72 h post-infarction (day 3). A possible role of cell damage in the elevation of serum total and lipid-bound sialic acid levels in these patients was also evaluated. In this study, 40 patients with myocardial infarction ranging in age from 42 to 68 years, and 26 healthy volunteers ranging in age from 45 to 71 years were included. Serum total sialic acid determination was carried out by the thiobarbituric acid method of Warren and lipid-bound sialic acfd by the method of Katopodis. Our data shows that a) there is a gradual increase in the levels of serum total sialic acid and lipid-bound sialic acid during the first three days after the acute myocardial infarction and b) the elevation in serum total sialic acid levels correlates with the elevation in lactate dehydrogenase activity only on day 1 following infarction. Therefore, either the shedding or secreting of sialic acid from the cell or cell membrane surface may be partly responsible for an increased serum sialic acid concentration especially on day 1 following myocardial infarction.

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.

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Paraoxonase-1 (PON1) and PON3 (PON3) are anti-atherosclerotic enzymes, synthesized primarily in liver and bound to HDL in circulation. The aim of the present study was to investigate the effects of therapeutic doses of lipoic acid on PON1 and PON3 protein levels, mRNA expression and arylesterase activity in liver. We treated HepG2 cells with 10, 40 and 200 μM lipoic acid for 72 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. PON1 and PON3 protein levels were measured by Western blotting, their mRNA expression was measured by quantitative PCR and arylesterase activity was measured spectrophotometrically. 200 µM lipoic acid caused a significant increase on PON1 and PON3 protein levels and arylesterase activity as compared with control, 10 µM and 40 µM lipoic acid-treated cells. 200 µM lipoic acid also caused a significant decrease on PON1 mRNA expression whereas on a significant increase PON3 mRNA expression as compared with control, 10 µM and 40 µM lipoic acid-treated cells. Our study showed that although lipoic acid up-regulates PON3 but down-regulates PON1 mRNA expression, it increases both PON1 and PON3 protein levels and arylesterase activity in HepG2 cells. We can report that lipoic acid may be useful for preventing atherosclerosis at therapeutic doses.

ÖZETAmaç: Oksidatif stres inflamatuvar barsak hastalıklarının patogenezinde önemli rol oynar. Bu çalışmada, antioksidan L-karnitinin deneysel kolitte, kolonda da sentez edilen paraoksonaz 1 enzim aktivitelerine ve oksidatif duruma etkisini inceledik. Gereç ve Yöntem: Wistar albino dişi sıçanlar kontrol, kolit, ön tedavi ve tedavi olmak üzere rastgele dört gruba ayrıldı. Kolit oluşturmak için kolit, tedavi ve ön tedavi gruplarına tek doz 1 mL asetik asit (%4) intrarektal olarak uygulandı. Ön tedavi grubuna kolit oluşturulmadan 1 saat önce, tedavi grubuna ise kolit oluşturulduktan 24 saat sonra 500 mg/kg L-karnitin tek doz halinde intraperitoneal olarak verildi. Tüm gruplar intrarektal uygulamadan 48 saat sonra sakrifiye edildi. Kolit varlığı histopatolojik olarak gösterildi. Serumda paraoksonaz, arilesteraz ve laktonaz aktiviteleri, total oksidan ve antioksidan durum, malondialdehit ve total sialik asit ölçüldü. Oksidatif stres indeksi formülden hesaplandı. Bulgular: Asetik asitle kolit oluşturulan grupta serum malondialdehit, total sialik asit, total oksidan durum ve oksidatif stres indeksi anlamlı olarak artarken, paraoksonaz, arilesteraz ve laktonaz aktiviteleri ve total antioksidan durum anlamlı olarak azaldı. L-Karnitin malondialdehit, total sialik asit, total oksidan durum ve oksidatif stres indeksinde anlamlı bir azalmaya yol açarken, sadece tedavi grubunun serum arilesteraz ve laktonaz aktivitelerinde anlamlı bir artışa yol açtı. Sonuç: Asetik asitle oluşturulan deneysel kolitte L-karnitin, arilesteraz ve laktonaz aktivitelerini arttırıcı, oksidatif stresi azaltıcı bir etkiye sahiptir. Bu nedenle L-karnitin, inflamatuvar barsak hastalıklarının tedavisinde yararlı olabilir. Anahtar Sözcükler: Deneysel kolit, L-karnitin, paraoksonaz, arilesteraz, laktonaz, oksidatif stres, malondialdehit, total sialik asit Çıkar Çatışması: Yazarlar arasında çıkar çatışması yoktur. ABSTRACT Aim:Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease. We investigated antioxidant L-carnitine effect on activities of paraoxonase 1 enzyme which is also synthesized in colon and oxidative status in experimental colitis. Material and Methods: Wistar albino female rats were divided into four groups randomly: control, colitis, pre-treatment and treatment groups. To induce colitis, single dose of 1 mL acetic acid (%4) was given intrarectally to colitis, pre-treatment and treatment groups. Single dose of 500 mg/kg L-carnitine was given intraperitoneally 1 hour before inducing colitis to pre-treatment group and 24 hours after inducing colitis to treatment group. All groups were sacrificied 48 hours after intrarectally administration. Existence of colitis was confirmed by histopathological changes. Paraoxonase, arylesterase and lactonase activities, total oxidant and antioxidant status, malondialdehyde, and total sialic acid were measured in serum. Oxidative stress index was calculated from the formula. Results: While serum malondialdehyde, total sialic acid, total oxidant status and oxidative stress ind...