Plasma Sialic Acid Levels Research Articles

Evaluation of sialic acid, malondialdehyde and glutathione levels in infertile male

Introduction and objectivesAround 15% of productive couples in the world are infertile. Recent years, biochemical mechanisms leads to male infertility are started to research. Redox regulation and oxidative stress (OS) show importance in the pathogenesis of infertility in male. Malondialdehyde (MDA) and Glutathione (GSH) are biochemical indicatives of sperm damage by reactive oxygen species (ROS). In addition, sperm are coated with a thick glycocalyx rich in sialic acids. It is aimed to determine and evaluate the differences between normozoospermic and oligozoospermic individuals according to sialic acid, MDA and GSH concentrations and correlations between spermyogram and these parameters. Material and methodsThis study was carried out on seminal plasma of individuals who admitted to Selcuk University Faculty of Medicine IVF Unit Andrology Laboratory. The groups were divided into two as normozoospermics (n=30, sperm concentration≥15million/mL), and oligozoospermics (n=30, sperm concentration<15million/mL). Spermyogram were evaluated regarding WHO (2010) Kruger criteria. GSH, MDA and sialic acid concentrations were analyzed in seminal plasma. Diagnostic performance of sialic acid has been determined with ROC curve analysis. ResultsSialic acid levels were significantly lower in Normozoospermic than Oligozoospermic individuals (p<0.0001), MDA and GSH levels were not differ significantly in both groups (p>0.05). Sialic acid correlated significantly with most of the spermyogram findings. When diagnostic performance of sialic acid was evaluated, the cut off value of sialic acid found as 4.175nmol/mL by ROC curve. ConclusionHigh seminal plasma sialic acid levels may be used as a biomarker and sialic acid is important determinant in oligozoospermia.

Neuraminidases 1 and 3 Trigger Atherosclerosis by Desialylating Low-Density Lipoproteins and Increasing Their Uptake by Macrophages.

BackgroundChronic vascular disease atherosclerosis starts with an uptake of atherogenic modified low‐density lipoproteins (LDLs) by resident macrophages, resulting in formation of arterial fatty streaks and eventually atheromatous plaques. Increased plasma sialic acid levels, increased neuraminidase activity, and reduced sialic acid LDL content have been previously associated with atherosclerosis and coronary artery disease in human patients, but the mechanism underlying this association has not been explored.Methods and ResultsWe tested the hypothesis that neuraminidases contribute to development of atherosclerosis by removing sialic acid residues from glycan chains of the LDL glycoprotein and glycolipids. Atherosclerosis progression was investigated in apolipoprotein E and LDL receptor knockout mice with genetic deficiency of neuraminidases 1, 3, and 4 or those treated with specific neuraminidase inhibitors. We show that desialylation of the LDL glycoprotein, apolipoprotein B 100, by human neuraminidases 1 and 3 increases the uptake of human LDL by human cultured macrophages and by macrophages in aortic root lesions in Apoe−/− mice via asialoglycoprotein receptor 1. Genetic inactivation or pharmacological inhibition of neuraminidases 1 and 3 significantly delays formation of fatty streaks in the aortic root without affecting the plasma cholesterol and LDL levels in Apoe−/− and Ldlr−/− mouse models of atherosclerosis.ConclusionsTogether, our results suggest that neuraminidases 1 and 3 trigger the initial phase of atherosclerosis and formation of aortic fatty streaks by desialylating LDL and increasing their uptake by resident macrophages.

Hexokinase activity were decreased in erythrocytes and increased in blood serum at the DM

BackgroundDiabetes Mellitus (DM) are combination of metabolic abnormalities due to chronic hyperglycemia state, which is reflects from cells to whole body. Hexokinase as a ubiquitous enzyme important in catch and clamp glucose from outer space inside of cells. Regulation of hexokinase activity would help to restore the glycemic control at the DM.With aim of determining hexokinase activity in erythrocytes and in blood serum 42 patients with type 2 DM were observed. Hexokinase activity calculated by colorimetric enzyme‐substrate reaction. In addition the fasting blood glucose, HbA1c, plasma sialic acids level and Erythrocytes sialidase activity were measured in this patients.Results shown that hexokinase activity were decreased in erythrocytes (78%, P&lt;0.05) and increased in blood serum (115%, P&lt;0.01), where the strong linkage between decreasing of erythrocytes hexokinase activity and increasing in the blood serum with fasting plasma glucose and HbA1c level were detected. Erythrocytes sialidase activity were increased (134%, P&lt;0.01) and blood plasma sialic acid level were increased (154%, P&lt;0.01) in patients with DM and indicated the degree of the structural and functional abnormalities on the cell surface. The strong linkage between erythrocytes sialidase activity and blood plasma sialic acids level were detected with blood plasma glucose and HbA1c level.ConclusionThe hexokinase activity were decreased in erythrocytes and increased in blood serum in patients with DM in depended with blood glucose and HbA1c and can be used as a marker of the cell membranes structural and functional abnormalities.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Benefits of Zubex beyond glycemic control: Evidence of the antiatherogenic effect.

To determine the effect of Zubex (aqueous extract of Curcuma longa linn, Iron murakab, Eugenia jambolana, Lin seed or flflax seed, processed egg shell calcium and Asphaltum) on plasma sialic acid (PSA) along with cardiovascular (CV) risk factors in streptozotocin-induced diabetic rats. Thirty male albino rats were divided into groups (1-6) with 5 rats in each group. Group 1 and 2 served as normal control (NC) and diabetic control (DC), respectively, and were given normal saline only. Groups 3-5 were given Zubex in different doses 100-400 mg/(kg day). Group 6 received glibenclamide 600 μg/(kg day) orally as a reference drug. Fasting plasma glucose (FPG) and PSA levels were determined at baseline after every 2 weeks for 10 weeks. The other parameters including blood lipids and hepatic enzymes were determined at baseline and at the end of the study. Finally, the liver was subjected to histological examination. Compared with DC group, Zubex treated groups showed signifificant decline in FPG levels (P<0.05). At the endpoint, the decrease in PSA concentration was significant (P<0.05) from baseline at the doses of 200 and 400 mg/(kg day) only and insignifificant at the dose of 100 mg/ (kg day). Statistically signifificant improvements were observed in blood lipids at the doses of 200 and 400 mg/kg (P<0.05) compared with DC; but, the improvement was insignifificant in low density lipoprotein-cholesterol and high density lipoprotein-cholesterol at the dose of 100 mg/ (kg day). Signifificant decreases were also found in hepatic enzyme levels at all the doses of Zubex (P<0.05). Histological examination showed marked improvement in streptozotocin induced liver injury after treatment of all the 3 doses of Zubex. Zubex could ameliorate PSA and other diabetic complications effectively and may be a useful alternative/adjuvant in diabetes treatment.

Effects of Diaceto-Dipropyl-Disulphide on Plasma Sialic Acid and Renal Tissue Thiol Levels in Alloxan Diabetic Rats.

Plasma sialic acid levels are elevated in Diabetes Mellitus (DM) patients with proteinuria. Renal damage is mainly caused by free radicals that are excessively generated in DM. Thiols play an important role in the cellular antioxidative defence mechanisms mainly through thiol-disulphide exchange reaction. Diallyl disulphide, a garlic oil principle component, is known for its anti-diabetic properties. Its structural analogue, Diaceto-Dipropyl Disulphide (DADPDS), is a less toxic and more palatable disulphide and possesses similar anti-diabetic actions. This study was undertaken to assess the usefulness of DADPDS in prevention of de-sialation of Glomerular Basement Membrane (GBM) in alloxan diabetic rats and to assess effect of DADPDS on renal tissue thiol levels. Rats were divided into Normal, Diabetic and DADPDS treated diabetic groups. Diabetes was induced by intraperitoneal injection (IP) of alloxan. DADPDS was fed by gastric intubation. Plasma Sialic acid was determined by Ehrlich's method and renal tissue thiol levels by Nitroprusside reaction method. This study showed a significant decrease (p<0.001) in plasma sialic acid, plasma glucose and renal tissue TBARS levels along with significant increase (p<0.001) in renal tissue thiol levels in DADPDS treated alloxan diabetic rats when compared to diabetic control rats. Hence it may be concluded that DADPDS helps in preventing de-sialation of GBM in alloxan diabetic rats and improves renal tissue antioxidant defence mechanisms, may be through thiol-disulphide exchange reaction and thereby exhibits a possible clinical use in prevention of renal complications like diabetic nephropathy.

Reduced negative surface charge on arterial endothelium explains accelerated atherosclerosis in type 2 diabetic patients

Reduced endothelial surface charge markedly increases the rate of LDL uptake into blood vessels. Previous work in the streptozotocin diabetic rat reported reduced endothelial surface charge. We compared endothelial surface charge density in internal mammary artery rings from patients with type 2 diabetes (n = 12) and from non diabetic patients undergoing coronary artery bypass grafting, and observed a substantial (52%) reduction in the former. This was associated with higher plasma sialic acid levels suggesting loss of sialic acid residues from the glycocalyx as a possible mechanism.

FR177995, a novel vacuolar ATPase inhibitor, exerts not only an inhibitory effect on bone destruction but also anti-immunoinflammatory effects in adjuvant-induced arthritic rats

There is considerable evidence that osteoclasts are involved in the pathogenesis of juxta-articular bone destruction in rheumatoid arthritis. Vacuolar ATPases (V-ATPases), which are highly expressed in the ruffled border membrane of osteoclasts, play a central role in the process of bone resorption, and V-ATPase inhibitors are effective in preventing bone destruction in several animal models of lytic bone diseases. Here, we evaluated for the first time the effects of V-ATPase inhibition in rats with adjuvant-induced arthritis (AIA) using FR177995, a novel V-ATPase inhibitor. FR177995 completely inhibited H(+) transport driven by V-ATPase, but exerted no effect on the H(+) transport activities of F- and P-ATPase, indicating that FR177995 is a specific inhibitor of V-ATPase. FR177995 acted directly on osteoclastic bone resorption and equally inhibited in vitro bone resorption stimulated by IL-1, IL-6 or PTH. In addition, FR177995 dose-dependently reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats. When FR177995 was administered to AIA rats once a day, the loss of femoral bone mineral density was significantly improved. Moreover, indicators of cartilage damage (arthritis score and glycosaminoglycan content in the femoral condyles) and inflammation parameters (paw swelling volume, erythrocyte sedimentation rate and plasma sialic acid level) were found to be unexpectedly ameliorated. These results strongly suggest that V-ATPase may be an interesting drug target in the treatment of rheumatoid arthritis.

Betaine prevents loss of sialic acid residues and peroxidative injury of erythrocyte membrane in ethanol‐given rats

To evaluate chronic ethanol toxicity on erythrocyte membrane and preventive action of betaine as a methyl donor, 24 male Wistar albino rats were divided into three groups: control, ethanol and ethanol plus betaine group. Animals were fed 60 ml diet per day for two months. Rats in the ethanol group were fed ethanol 8 g/kg/day. The ethanol + betaine groups were fed ethanol plus betaine (0.5% w/v). After two months, all animals were killed. Malondialdehyde (MDA) and sialic acid (SA) levels were determined in plasma samples. Osmotic fragility tests were performed on whole blood samples and erythrocyte membrane thiol contents were determined using membrane suspensions. Plasma MDA levels in ethanol-given rats were increased significantly compared to the control group of rats (p < 0.05). MDA in the betaine group was significantly lower than that in the ethanol group (p < 0.05). Erythrocyte membrane thiol contents in ethanol group were decreased compared with those of the control group (p < 0.05). Thiol contents were increased slightly after betaine therapy, but this increase was not statistically significant (p > 0.05). Plasma sialic acid levels in the ethanol group were significantly higher than in the control group (p < 0.05). Sialic acid was decreased in the betaine group compared to the ethanol group (p < 0.05). In the osmotic fragility test, we observed that chronic ethanol consumption increased erythrocyte hemolysis. Betaine protected against ethanol-induced hemolysis. Our findings show that chronic ethanol administration affects erythrocyte membrane properties and this may be related to oxidative stress. Betaine protects erythrocyte membrane alterations against chronic ethanol toxicity. Therefore betaine as a nutritional agent, may protect ethanol induced clinical problems associated with membrane abnormalities.

Curcumin's Effects on Sialic Acid Level and Sialidase Activity in Ehrlich Ascites Tumor Bearing Mice.

In this study, we determined curcumin's anticancer and chemopreventive effects in mice bearing Ehrlich ascites tumor by evaluation of cancer biomarkers, sialic acid level and sialidase activity. Both plasma sialic acid level and sialidase activity increased significantly in the mice group with Ehrlich ascites tumor. When the tumor groups fed with curcumin and fed with sesame oil were compared, sialic acid level and sialidase activity in ascites fluid significantly reduced in the group fed with curcumin in addition to the increases of plasma sialic acid level and sialidase activity. The tumor group fed with curcumin lived twice longer than the one fed with sesame oil. Curcumin as a phenolic compound decreased all these parameters in Ehrlich ascites tumors and lengthened survival by 88% in the mice with tumor. We concluded that curcumin has anticancer activity.

Relationship Between Fibrinogen Protein and Fibrinogen Function in Postmyocardial Infarction Patients

The present study investigates the association between increases in the concentration and function of plasma fibrinogen in two groups of patients with chronic ischemic heart disease (11 with recurrent ischemic events and 19 free of these episodes) and in 34 healthy controls. The fibrinogen function index (fibrinogen function per unit of fibrinogen protein) (FgFI) was used as a measure of the fibrinogen clotting potential. The prothrombin fragment 1+2 (F1+2) and thrombin–antithrombin (TAT) were used as procoagulant markers. Plasma sialic acid (SA) was also evaluated as an inflammatory marker. No differences were found between FgFI (1.06±0.13 vs. 1.02±0.13), F1+2 (1.2±0.5 vs. 1.1±0.4 nmol/l) and TAT (2.5±1.3 vs. 2.5±0.7 μg/ml) in postinfarction patients without recurrent coronary ischemic events and the control group. However, postinfarction patients who suffered recurrent coronary ischemic events had significantly higher FgFI than patients without these symptoms (1.19±0.09 vs. 1.06±0.13), P<.01) and than the control group (1.19±0.09 vs. 1.02±0.13, P<.001). Moreover, the F1+2 (1.4±0.5 vs. 1.1±0.4 nmol/l, P<.05) and TAT (3.6±3.3 vs. 2.5±0.7 μg/ml, P<.05) were significantly higher in patients who suffered recurrent coronary ischemic events than in the control group. However, F1+2 and TAT were not different between patients with and without these symptoms. The fibrinogen protein (Fg-protein) concentration and high molecular weight fibrinogen (HMW-Fg) levels were significantly higher in both postinfarction patient groups than in the control group and in postinfarction patients with recurrent coronary ischemic events than in postinfarction patients without these symptoms. The plasma SA levels were significantly increased in postinfarction patients with and without recurrent coronary ischemia as compared with the control group. A positive correlation was found between fibrinogen and SA levels ( r=.5, P<.01). In conclusion, our study indicates that the procoagulant factors, among which we include fibrinogen, F1+2 and TAT play a very active role in recurrent ischemic events in postmyocardial infarction patients. High plasma concentrations of both fibrinogen and SA suggests that fibrinogen becomes elevated as a consequence of inflammatory processes. The FgFI as an indicator of clotting potential of fibrinogen appears to be associated with ischemic events in chronic coronary artery disease.

Plasma sialic acid in animal models of diabetes mellitus: Evidence for modulation of sialic acid concentrations by insulin deficiency

An elevated circulating sialic acid concentration is a risk factor for cardiovascular disease. Serum sialic acid levels are elevated in NIDDM but not in uncomplicated IDDM. To study why sialic acid is increased in some types of diabetes, we assayed plasma sialic acid in various animal models of diabetes: obese (ob/ob) mice, before and after streptozotocin treatment, neonatal streptozotocin-treated (nSTZ) rats, and diabetic BB rats during and after insulin treatment. In obese mice, which exhibit moderate hyperglycemia and marked hyperinsulinemia, plasma sialic acid was decreased by 45% (fed) and 42% (fasted), compared to lean controls. Fasting reduced plasma glucose and insulin but increased sialic acid in the obese and lean mice. There was a negative correlation (r = −0.84, P < 0.001) between log plasma insulin and sialic acid in the lean and obese mice. The plasma sialic acid:globulin ratio was reduced by 35% in obese mice vs. lean controls, indicating that there may be altered sialylation of glycoproteins in obese mice. Streptozotocin treatment of obese and lean mice reduced plasma insulin but increased sialic acid. In nSTZ rats, hyperglycemia was associated with mild hypoinsulinemia, but not significantly different from control animals, and sialic acid was not altered. In diabetic BB rats, plasma glucose rose from a mean of 4.9 to 23.5 mM 48 hr after insulin withdrawal but sialic acid did not change. We conclude that an elevated plasma sialic acid level is associated with marked insulin deficiency, rather than hyperglycemia per se. The magnitude and speed of this change in sialic acid varies between species.

Increase of plasma sialic acid upon UV-B irradiation in mouse.

In many inflammatory conditions including burns, the plasma sialic acid level rises as an acute responder. Sunburn is a kind of burn. In this study, sunburn was experimentally caused in mice by UV-B irradiation and their plasma sialic acid levels were measured. The levels increased, and reached the maximum 3 d after irradiation. This level was maintained for about 2 d, then it returned to normal within about one week. The increase in the level correlated with the UV dose and the severity of inflammation resulting in sunburn. This assay system was applied to assess the virtue of UV-cut cream in experimental sunburn.

Hyperviscosity syndrome in disseminated breast adenocarcinoma

Circulation within the bloodstream of mucin derived from mucin-producing adenocarcinomas has been documented infrequently but has been associated with vascular occlusion, organ infarction, and hyperviscosity. The nature of the mucin and the therapeutic role of plasmapheresis in this condition has not been reported. A 64-yr-old female, who had undergone a mastectomy 3 yrs previously for an infiltrating mucinous breast adenocarcinoma, presented with dementia. A blood film showed marked rouleaux and a bluish background. No abnormal bands were detected on plasma protein electrophoresis. Blood, serum and plasma viscosity were above the range of readability of the viscometer. A bone marrow biopsy showed replacement with tumor similar to the original. Repeated plasmaphereses substantially reduced viscosity and temporarily improved her mental state. Post mortem revealed numerous infarcts with eosinophilic mucoid material in the lumen of many small vessels. That the offending plasma constituent was a sialomucin was suggested by mucin stains of the tumor and peripheral blood, a plasma sialic acid level 10 x normal and a substantial fall in viscosity after in vitro treatment of plasma with neuraminidase.

Plasma Sialic Acid Alterations in Neoplastic Diseases

The several types of neoplastic transformations are accompanied by alterations in the composition of cell glycoproteins, which are major structural components of cell surfaces. One such observed alteration is in the level of sialic acid on the cell surface. In the present investigation, plasma sialic acid levels were measured in normal volunteers and neoplastic patients using thiobarbituric acid spectrophotometric methods. The mean plasma sialic acid level from 124 normal volunteers was 3.0 mumol/ml. The mean for 20 non-malignant patients was 3.2 mumol/ml. Such observed mean values of sialic acid were 3.7 mumol/ml in 64 breast cancer patients, 5.1 mumol/ml in 22 lung cancer patients, 4.1 mumol/ml in 20 colon patients, and 5.0 mumol/ml in 26 patients having ovarian, cervix, pancreas, prostate, thyroid, uterine, squamous cell, esophageal and endometrial cancers. Serial determinations of plasma sialic acid in 15 patients correlated well with the progression and regression of disease. These results indicate that plasma sialic acid levels are elevated over control levels in the different types of cancer patients studied. Assay of plasma sialic acid is not sensitive enough to be used for screening, but could be used as a prognostic determinant in a variety of neoplastic conditions.

Sialic acid, sialyltransferase and neuraminidase levels in maternal plasma, urine and lymphocytes during pregnancy and post-partum period — a longitudinal study in women

The total sialic ( N-acetylneuraminic acid) levels were serially determined in maternal plasma, urine and lymphocytes during human pregnancy and post-partum period. The enzymes, sialyltransferase and neuraminidase, were also examined in the plasma samples. The sialic acid content of plasma and urine (expressed in terms of the creatinine content in urine) was elevated during pregnancy and increased with advancing gestation ( P < 0.001). A few days (0–6) prior to parturition there was a significant ( P < 0.01) fall in the plasma sialic acid levels, which subsequently increased again in the post-partum period (1–14 days), reaching values even greater than that observed during pregnancy. On the other hand, there was no decrease in the urinary sialic acid levels before delivery, and the post-partum values in urine, though higher than the values obtained in non-pregnant women, were not significantly greater than the levels observed during pregnancy. The sialic acid levels in lymphocytes were not altered during pregnancy. There was also no statistically significant change in serum sialyltransferase activity at any stage of pregnancy or post-partum period, while neuraminidase was not detectable in any of the plasma samples. The results are discussed with reference to the role of circulating sialic acid during pregnancy.