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.

RNA, DNA and total protein levels in subcellular fractions of human brain tumors.

The intracellular distributions of the nucleic acids DNA and RNA and of total proteins were investigated in different types of human brain tumors and were compared with those of normal brain tissue. The tumor types studied were: meningioma, astrocytoma, and glioblastoma multiforme. Nucleic acids and total proteins were found to increase in the nuclear fraction of all tumoral tissues as compared with normal brain tissue. Another important finding is that the rate of the increase of these parameters is not proportional to the degree of malignancy of the tumor.

Hydrogen peroxide detoxication by catalase in subcellular fractions of human brain tumors and normal brain tissues.

Hydrogen peroxide detoxication by catalase was found to be significantly lower in human brain tumoral tissue as compared with normal brain tissue. As to the subcellular distribution of catalase activity, the tumoral tissue showed a decrease in the nuclear and mitochondrial fractions and an increase in the supernatants.

Acid and alkaline phosphatase activities in homogenates and subcellular fractions of human brain tumors.

This study is a quantitative analysis of acid and alkaline phosphatase activity in human brain tumor homogenates and subcellular fractions, in parallel with normal brain tissue. Glioblastoma multiforme, meningioma, astrocytoma and normal tissue samples were separated by ultracentrifugation into five subcellular fractions: nuclei (N), mitochondria (M), microsomes (P), ribosomes (R) and supernatant (S). These two phosphatases showed significant increase in astrocytoma and meningioma tissue homogenates, compared with normal brain tissue. Alkaline phosphatase levels were determined to increase significantly in glioblastoma multiforme tissue homogenates as compared with normals, while those of acid phosphatase were observed to decrease. The results of this investigation also indicate that the subcellular distributions of acid and alkaline phosphatase show differences in the different tumor types. This observation is evidence against metabolic uniformity in tumoral tissue.

Human brain tumor phosphoglycerides.

This study is a qualitative and quantitative comparative analysis of the phosphoglycerides found in human brain tumors and normal brain tissue. Astrocytomas, glioblastomas, meningosarcomas and ependymomas were studied and, in all of these, the total phosphoglyceride levels were found to be significantly lower than in normal controls. Fractionation of the phosphoglycerides by thin-layer chromatography showed definite qualitative and/or quantitative differences in the phosphoglyceride fractions of tumor tissues in comparison with normal brain tissue.

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).

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.

Subcellular localization of sialic acid in human brain tumors.

The subcellular localization of sialic acid has been investigated in various types of human brain tumors, such as astrocytoma, meningioma and primary malignant lymphoma. High levels of sialic acid were observed in the microsomal fraction of all types of tumors. However, there was no significant difference between values obtained in meningioma, primary malignant lymphoma, and normal tissue, in the fractions examining nucleus, mitochondria and supernatant.

Xanthine oxidase levels in human brain tumors.

Xanthine oxidase is most recognized for its role as the rate-limiting enzyme in nucleic acid degradation through which all purines are channelled for terminal oxidation. The enzyme serves as a source of oxygen-derived free radicals which induce both cellular injury and edema as well as changes in vascular permeability. In the study we compared xanthine oxidase levels of human brain tumors with normal brain tissues. Statistical evaluation of our results shows significantly higher xanthine oxidase levels in tumoral brain tissues. However, xanthine oxidase has not any significance for the differentiation of tumor types among each others. The oncotypes studied were meningioma and astrocytoma.

Tissue lipid composition of human gliomas and meningiomas.

This study is a comparative analysis of some lipid fractions in human brain tumors and normal brain tissue. Gliomas and meningiomas were studied and in these tumors while total lipid, total and free cholesterol and total phosphoglyceride levels were found to be significantly lower than in normal controls, the difference in esterified cholesterol levels was found to be insignificant. No significant differences in lipid fractions existed between gliomas and meningiomas except total and esterified cholesterol values.

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).

Alterations of serum lipids and lipoproteins in breast cancer.

Serum triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low density lipoprotein (VLDL) cholesterol levels were quantified in Stage I and Stage IV breast cancer patients in order to evaluate the changes in serum lipids and lipoproteins in the early and advanced stages of the disease. When compared with data from age-matched healthy females, fasting serum triglycerides and VLDL cholesterol levels were found to be significantly increased and HDL cholesterol levels significantly decreased in patients with breast cancer. Furthermore, a significant increase in triglycerides and VLDL cholesterol and decreases in total, HDL and LDL cholesterol levels were demonstrated in patients with Stage IV disease when compared to those with Stage I breast cancer. No significant difference was found in total and LDL cholesterol between Stage I breast cancer patients and healthy controls.

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).

Serum and tissue total sialic acid as a marker for human thyroid cancer.

In this study, serum and tissue sialic acid levels in various histopathological types of thyroid cancer were measured and were found to be significantly higher than those measured in the control group. The amount of sialic acid in tissue was 2.8 +/- 1.42 mg/100 mg protein while the serum level was 79.2 +/- 6.6 mg per dl. The rise in tissue and serum sialic acid levels was relatively non-specific with respect to type of cancer as they depend on the tumor burden only. Neither were they related to age, sex or duration of cancer. The serum sialic acid levels increased during the few days following thyroidectomy and returned to normal thereafter. The sialic acid determination appeared to be an important criterion in patient follow-up and evaluating therapeutic response.

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.

Leucocyte superoxide dismutase levels in acute and chronic leukemias.

Superoxide dismutase "SOD" enzyme levels in leucocytes of patients with acute and chronic leukemia, were measured by using Misra and Fridovich's epinephrine method. In all types of leukemia, the SOD levels were found to be significantly higher than normals. However, these levels decreased to normal in remission. No relationship was found between the SOD level and types of leukemia. The absence of relationship between the increase in SOD level and various clinical parameters suggests that this increase is the result of a disturbed gene expression in the stem cells. Hence it is of interest to ascertain the effect of the chemotherapy leading to the normalization of the SOD levels.

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.

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.