The effects of different doses of melatonin on lipid peroxidation in diet-induced hypercholesterolemic rats.

This study aims to see in an animal experiment how differently the low and high doses of melatonin affect the antioxidant status and peroxidation of lipids. Forty-two male Wistar-Albino rats weighing about 200 gr (180-220) aged 6-7 months were used. Of these rats, 12 were fed with normal rat chow for 12 weeks. The latter ones were divided into two groups, each containing 6 rats. Group 1 (control group) received daily intraperitoneal injections of NaCl (0.9%; w/v). Group 2 was injected ethanol daily (4%; v/v; i.p.) to see the effects of ethanol in which we dissolved melatonin. Thirty rats were fed with a diet enriched with cholesterol (2%; w/w), cholic acid (0.5%; w/w) and propilthyouracil (0.5%; w/w) for 12 weeks. These rats were divided into three groups each containing 10 rats. The low-dose group received melatonin 1 mg/kg/d; i.p. (group 3), the high-dose group received melatonin in a dose of 10 mg/kg/d; i.p. (group 4), and only the cholesterol group did not get any vehicle (group 5). Total cholesterol (TC), LDL cholesterol (LDL-C), total antioxidant capacity (TAC), oxidized LDL (oLDL) and TBARS lelvels were measured in all groups. The produced high-cholesterol diet increased LDL cholesterol. Melatonin decreased the extent of this plasma lipoprotein increase and also prevented the oxidation of it. This effect was clearer when the dose was higher. Antioxidant status seems to be also dose-dependent (Tab. 2, Ref. 33).

Investigation of zinc and copper levels in methimazole-induced hypothyroidism: relation with the oxidant-antioxidant status.

Thyroid hormones are associated with the oxidative and antioxidative status of the organism. Depression of metabolism by hypothyroidism has been reported to decrease oxidant production and thus protect tissues against oxidant damage. The purpose of the present study was to investigate Zn and Cu levels in MMI-induced hypothyroidism and to show whether there is a connection between these trace elements and the oxidant-antioxidant status in experimental hypothyroidism. 3-Nitrotyrosine was measured as a marker of nitro-oxidative stress. In order to examine the antioxidant status of MMI-induced hypothyroidism in rats, GSH and SOD levels were determined as well. Significantly decreased 3-nitrotyrosine, Cu and Zn levels were observed in our experimental model when compared with the controls. On the other hand, GSH and SOD levels remained constant. It may be suggested that Cu and Zn serve as antioxidant molecules and exert their effects in an indirect manner to reduce oxidative stress in experimental hypothyroidism.

TBARS, carnitine, and reduced glutathione levels in human bladder carcinoma.

In this study, we investigated tissue levels of reduced glutathione (GSH) and carnitine as well as thiobarbituric acid reactive substances (TBARS, as a marker of lipid peroxidation) levels in bladder carcinoma and control group of patients. The average GSH, carnitine and TBARS levels for tumor group were respectively 7.11 +/- 3.3 micro g/mg protein, 1.81 +/- 0.39 nmol/mg protein, and 4.29 +/- 3.2 micro mol/mg protein, versus 14.45 +/- 4.11 micro g/mg protein, 2.14 +/- 0.66 nmol/mg protein, and 2.3 +/- 0.6 micro mol/mg protein for normal bladder tissues. Thus, tissue reduced glutathione levels (GSH) were significantly lower in patients as compared with the control group (p < 0.001) whereas average TBARS levels in the tumor group were found to be higher than those in control group. The average tissue carnitine levels in the patient group were found to be lower compared with the control group but the difference was not statistically significant (p > 0.05).

Carbohydrate-deficient transferrin and sialidase levels in coronary heart disease.

Transferrin is a N-glycosylated glycoprotein and plays an important role in iron transport from sites of absorption and storage to sites of utilization. The main component of normal serum transferrin contains two biantennary glycans, each consisting of 2 mol of sialic acid (Tetrasialo transferrin). Normal serum also contains small amounts of tri- and disialotransferrin. We have undertaken this study to investigate the levels of serum carbohydrate-deficient transferrin (Desialotransferrin) and sialidase levels in patients with coronary heart disease. In patient group, serum desialotransferrin and sialidase levels were found to be significantly higher than control group (p < 0.01 and p < 0.001, respectively). We conclude that increased activity of sialidase may be responsible for increased desialotransferrin in patients with coronary heart disease. Serum desialotransferrin levels may be useful critaria to diagnosis and pathogenesis of coronary heart disease.

Tissue and serum sialidase levels in breast cancer.

Breast cancer is both one of the most common and one of the most treatable of all human malignancies. It has been suggested by various investigators that sialic acid increases in the sera of cancerous patients. In cancer patients, an increase in the levels of serum sialic acid may also be due to an increase in the activity of serum or tissue sialidase. The purpose of the present investigation was to determine whether the concentration of sialidase in serum and breast tissue could be used as a tumor marker in breast cancer. In this study; serum sialidase levels in 26 patient with breast cancer and 31 controls were found to be 77.04+/-25.07 U/l and 55.56+/-7.50 U/l, respectively. The mean tissue sialidase levels in 26 breast cancer patients and 13 controls were 39.76+/-17.03 U/g protein and 14.30+/-7.09 U/g protein, respectively. Serum and tissue sialidase levels in breast cancer were significantly higher than those found in the control group (P < 0.001). The mean serum and tissue sialidase levels in 14 Grade I-II and 12 Grade III breast cancer patients were found to be 67.73+/-11.87 U/l and 33.41+/-12.17 U/g protein and 87.89+/-31.94 U/l and 47.17+/-19.30 U/g protein, respectively. Also we found a significant difference between the levels of serum and tissue sialidase in Grade I-II and III (P < 0.05).

Total acid soluble and insoluble carnitine levels in human brain tumors.

Carnitine has two main functions, i.e., transporting long-chain fatty acids into the mitochondrial matrix for beta-oxidation to provide cellular energy and modulating the rise in intramitochondrial acyl-CoA/CoA ratio, which relieves the inhibition of many intramitochondrial enzymes involving glucose and amino acid catabolism. The present study examined the acid soluble carnitine (ASCAR) acid insoluble carnitine (AICAR) and total carnitine (TCAR) concentrations of 50 human brain tumor tissues and 11 normal brain tissues. The ASCAR levels significantly higher in gliomas and meningiomas than brain, however similar to brain in metastatic adenocarcinomas. AICAR levels were lower than brain in all tumors with the exception of a medullablastoma. TCAR levels were similar to brain in all tumor types. Decreased AICAR levels may be due to increased utilization of lipids or enhanced phospholipid and cholesterol synthesis which is need for increased membrane synthesis or formation of eicosanoids. Also decreased concentrations may be a reflection of camitine and its acylesters role in preserving the physiologic membrane structure function from oxidative damage.

Alterations in superoxide dismutase activities, lipid peroxidation and glutathione levels in thinner inhaled rat lungs: relationship between histopathological properties.

Paint thinner has widespread use in industry. The use of thinner among children as a narcotic agent has become a social and health problem. There is some evidence that organic solvents may express their toxicity by the way of reactive oxygen species (ROS) induced cell damage. ROS has been shown to induce lipid peroxidation in biological membranes. This study examined peroxidative and histopathological changes in the rat lung, during 5 weeks of thinner inhalation. Significant increases were found in lipid peroxidation (MDA+4-DHA) levels related to the duration of inhalation. As opposed to increases in the lipid peroxidation levels, significant decreases in superoxide dismutase activities and glutathione levels were observed from the third inhalation week to the end of the fifth week. At the beginning of the inhalation slight inflammatory changes, intraalveolar and interstitial extravasation and oedema in lung parenchyma were noted. As the inhalation period extended, chronic inflammatory changes, alveolar epithelial proliferation, collapse, emphysematous changes and interstitial fibrosis in lung were detected.

The distribution of tissue fibronectin and sialic acid in human breast cancer.

Our findings indicate that sialic acid and fibronectin levels in breast tumors are higher than those in normal tissues. The mean tissue fibronectin and sialic acid concentrations for patients with breast cancer were 30.90 +/- 9.68 microg/mg protein and 21.60 +/- 9.35 microg/mg protein, respectively, and for normal controls were 12.47 +/- 5.69 microg/mg protein, respectively. Tissue fibronectin and sialic acid can be important markers for human breast cancer.

Profiles of the fatty acids in the plasma membrane of human brain tumors.

Several studies demonstrated that certain fatty acids have specific effects on tumor cells. n-3 series fatty acids (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) may suppress the carcinogenesis, whereas n-6 series fatty acids (arachidonic acid, linoleic acid) may exert tumor promoting effects. In this study, 19 patients with various brain tumors and 12 control brain tissues were studied. n-3, n-6, n-9 unsaturated fatty acids and certain saturated fatty acids levels were measured in the plasma membrane of tumor or control brain tissues by capillary gas chromatography. We found that the level of docosahexaenoic acid from n-3 series fatty acids was significantly lower in gliomas and meningiomas than controls (p = 0.000). Total n-3 fatty acids level was also significantly lower in tumors than controls (p = 0.000). The levels of linoleic acid, arachidonic acid and dihomogamma linolenic acid from n-6 series were significantly higher in gliomas and meningiomas compared with controls (p = 0.000). Total n-6 fatty acids level was also significantly higher in tumors than controls (p = 0.000). Furthermore, in total n-9 fatty acids, total unsaturated fatty acids and total saturated fatty acids levels, there were no significant differences in gliomas and meningiomas compared with controls (p = 0.6840, p = 0.4388 and p = 0.4343, respectively). This findings suggest that n-6 fatty acids can act as a tumor-promoting agent in human brain tumors.

Prostaglandin E2 levels in human brain tumor tissues and arachidonic acid levels in the plasma membrane of human brain tumors.

Arachidonic acid is stored in the cell membrane and released when the cell is activated by appropriate stimuli. It is the substrate for prostaglandins. Both experimental and human tumors often synthesize high levels of prostaglandins, most notably prostaglandin E2 (PGE2). Some experiments suggest that these compounds increase tumor growth through their actions on host immunocytes. In this study, 22 patients with various brain tumors and 12 control brain tissues were studied. PGE2 levels in tissue samples were measured by ELISA. Arachidonic acid levels in the plasma membrane of tissue samples were analyzed by capillary gas chromatography. The levels of PGE2 were significantly higher in gliomas (n = 10) and meningiomas (n = 7) compared with control tissues (P = 0.000 and P = 0.000, respectively). Also, PGE2 levels in meningiomas were significantly higher than in gliomas (P = 0.000). Arachidonic acid levels in the plasma membrane of gliomas (n = 9) and meningiomas (n = 6) were significantly higher than in the control tissues (P = 0.000 and P = 0.000, respectively). These results suggest that the increased production of PGE2 may suppress the immune system and play an important role in tumor growth.

The importance of Lp(a)-fibronectin interaction in atherogenesis.

An elevated concentration of lipoprotein (a) (Lp(a)) in serum has been considered a risk factor for coronary heart disease by various investigators. The apo(a) portion of Lp(a) binds to the carboxyterminal heparin binding domain of fibronectin. Lp(a) bound to fibronectin is internalized through the fibronectin receptor pathway and thereby causes increased accumulation of lipid and foam cell formation. In the present study, fibronectin and Lp(a) concentrations have been assayed in patients with coronary heart disease (CHD) and healthy subjects. Serum total cholesterol, triglyceride, LDL, VLDL and HDL cholesterol levels in patients with coronary heart disease were significantly different from the control group (p < 0.001). Plasma fibronectin (p < 0.05) and serum Lp(a) (p < 0.001) levels were found to be significantly elevated when compared with the control group.

The molecular markers of hemostatic activation on coronary artery disease.

Endothelial cells, circulating platelets, and proteins of the coagulation and fibrinolytic systems are known to contribute to the hemostatic processes. Various molecular markers of hemostatic alteration are found in increased amounts in the circulation during the activation of this process. In this study, we investigated serum lipoprotein (a) and plasma platelet factor 4, beta-thromboglobulin, thrombin-anthithrombin complex, fibrinopeptid A, D-dimer, tissue plasminogen activator, tissue plasminogen activator inhibitor, and fibronectin levels in patients with coronary artery disease. The levels of all these markers were found to be significantly higher as compared to the control group. Our findings suggest that patients with coronary artery disease have greater blood coagulability than controls, and the use of molecular markers has become greatly important in clinical practice.

Plasma Lp(a) and t-PA-PAI-1 complex levels in coronary heart disease.

In this study we investigated serum Lp(a) and plasma t-PA-PAI-1 complex levels in patients with coronary heart disease (CHD). Serum total cholesterol, triglyceride, LDL and VDL cholesterol levels (p < 0.001) and HDL cholesterol levels (p < 0.01) in patients group were found to be significantly different from those in control group. The mean Lp(a) and t-PA-PAI-1 complex levels in patients with coronary heart disease were significantly higher as compared to control group (p < 0.001). This data indicate that the elevated levels of serum Lp(a) and plasma t-PA-PAI-1 complex may play an important role in the pathogenesis of coronary atherosclerosis.

The prognostic importance of fibronectin and sialic acid levels in human pituitary adenomas.

In this study, fibronectin and sialic acid levels were determined in human pituitary adenomas. The mean fibronectin and sialic acid levels for human pituitary adenomas were found to be 31.64 +/- 15.82 microgram/mg protein and 21.90 +/- 9.82 microgram/mg protein, respectively, versus 6.30 +/- 2.96 microgram/mg protein and 9.88 +/- 2.81 microgram/mg protein for the normal brain tissues. Fibronectin and sialic acid levels were significantly higher (P < 0.001) in human pituitary adenomas than the normal brain tissues. In human infiltrative and non-infiltrative pituitary adenomas, the mean fibronectin and sialic acid levels were found to be 40.87 +/- 15.90 microgram/mg protein, 27.59 +/- 11.10 microgram/mg protein and 22.40 +/- 9.51 microgram/mg protein, 16.21 +/- 3.20 microgram/mg protein, respectively. Fibronectin and sialic acid levels were slightly elevated (P < 0.05) in human infiltrative pituitary adenomas compared with non-infiltrative adenomas.

Tissue sialic acid and fibronectin levels in human prostatic cancer.

We investigated the tissue concentration of sialic acid and fibronectin in patients with prostatic cancer. The mean sialic acid and fibronectin levels in patients with prostatic cancer were 19.02 +/- 6.30 micrograms/mg protein, respectively versus 13.01 +/- 4.53 micrograms/mg protein and 11.77 +/- 6.74 micrograms/mg protein for normal prostatic tissues. Sialic acid and fibronectin levels in cancerous patients were significantly higher than in the control group (P < 0.05).

The relationship between the electrophoretic mobility of lipoproteins and coronary heart disease.

Low density lipoproteins (LDL) in patients with coronary atherosclerosis have a substantially lower content of sialic acid when compared with the LDL from healthy subjects. Desialylated LDL have smaller sizes and greater electrophoretic mobilities than sialylated ones. Desialylated LDL may be responsible for the accelerated development of foam cells in atherosclerosis. In the present study, we investigated a relationship between the electrophoretic mobility of lipoproteins and the number of significantly obstructed vessels in patients with coronary heart disease (CHD). Our findings indicate that when the number of significantly obstructed vessels is increased, the electrophoretic mobility of lipoproteins is high. We also investigated the possible role of serum sialidase activity on lipoprotein desialylation in patients with coronary heart disease. In patients with single vessel disease (p < 0.01) and double-triple vessel disease (p < 0.001) the mean serum sialidase activity was significantly higher than in the control group.

Tissue fibronectin levels of human prostatic cancer, as a tumor marker.

In this study, tissue fibronectin levels have been assayed in human prostatic cancer, benign prostatic hyperplasia and normal prostatic tissue. The mean tissue fibronectin levels for prostatic cancer, benign prostatic hyperplasia and normal groups were found to be 20.22 +/- 8.66 micrograms/mg protein and 11.77 +/- 6.74 micrograms/mg protein, respectively. In the malignant group, the mean fibronectin concentrations, appeared to be significantly higher than normal, (p < 0.05). On the other hand, fibronectin levels of benign prostatic hyperplasia were found to be statistically insignificant in comparison to the normal group (p > 0.05).

Plasma fibronectin and sialic acid levels in various types of human brain tumors.

In this study, fibronectin and sialic acid concentrations were determined in plasma from patients with pituitary adenoma, meningioma and glioma, and, from controls. The mean plasma fibronectin levels in patients with pituitary adenoma, meningioma and glioma (p < 0.001) appeared to be significantly lower than controls. On the contrary, the mean plasma sialic acid values in patients with pituitary adenoma (p < 0.01), and glioma (p < 0.001) were significantly higher as compared to normal plasmas. The mean plasma sialic acid values in patients with meningioma were not different from those in controls. Also, the mean fibronectin levels in patients with glioma were found to be significantly higher than those in patients with meningioma (p < 0.05).

Fibronectin and sialic acid levels in human meningiomas and gliomas.

In this study, fibronectin and sialic acid levels have been assayed in human meningiomas and gliomas. The mean fibronectin and sialic acid levels for human meningiomas were 22.01 +/- 9.70 micrograms/mg protein and 19.58 +/- 4.89 micrograms/mg protein, respectively, and for human gliomas were 27.30 +/- 13.70 micrograms/mg protein and 25.67 +/- 11.60 micrograms/mg protein, respectively, versus 9.23 +/- 5.40 micrograms/mg protein and 13.50 +/- 4.30 micrograms/mg protein for normal brain tissues. Fibronectin and sialic acid levels were significantly higher in human meningiomas (P < 0.01 and P < 0.05) and gliomas (P < 0.001 and P < 0.01) than control group. Also the mean fibronectin and sialic acid levels were found to be 18.27 +/- 7.08 micrograms/mg protein and 17.04 +/- 6.25 micrograms/mg protein in Grade I-II and 32.60 +/- 15.00 micrograms/mg protein and 29.50 +/- 11.60 micrograms/mg protein in Grade III-IV gliomas, respectively. Fibronectin and sialic acid levels were significantly higher in Grade III-IV gliomas than Grade I-II gliomas (P < 0.05).

Changes in the activity of antioxidant enzymes (SOD, GPX, CAT) after experimental spinal cord injury.

We determined time dependent changes in the levels of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) at 1, 4 and 24 hours after standardized reversible spinal cord injury in rats. In each segment (rostral, lesion, caudal) enzyme activities at 1, 4 and 24 hours were not significantly different. Without time limitation we have found that SOD and GPx activities were not significantly different (p > 0.05), but CAT activity was significantly high (p = 0.008) in the lesion segment than the rostral and caudal segment. According to our results we suggest that one of the main reason for tissue damage during such a spinal cord trauma model may be neither H2O2 nor H2O2 derived radicals.