Increased lipid peroxidation in growth hormone-deficient adult patients.

OBJECTIVES: Growth hormone (GH) deficiency in adults is associated with a higher risk of atherosclerosis and cardiovascular disease. It has recently been suggested that enhanced oxidative stress may be implicated in vascular (and probably other) disturbances, occurring in GH-deficient subjects. The aim of the study was to evaluate serum levels of lipid peroxidation (LPO) products in adult patients with severe GH deficiency during insulin tolerance test (ITT), and to estimate the relationships between LPO and GH, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and other parameters of metabolic processes. MATERIAL AND METHODS: Twelve adult patients with severe GH deficiency hospitalized in our department and 12 healthy volunteers, matched for sex, age and body mass index (BMI), were enrolled in the study. Peripheral blood was collected during ITT. The concentrations of malondialdehyde + 4-hydroxyalkenals (MDA+4-HDA), as an index of LPO, were measured in blood serum. RESULTS: Serum LPO level was approximately twice as high in GH-deficient patients as in the controls at each time point of ITT. A positive correlation was found between bone mineral density in the lumbar spine and GH concentration in GH-deficient patients. A positive correlation was found between LPO and BMI in the controls, but no such correlation was observed in GH-deficient patients. CONCLUSION: The increased LPO in GH-deficient patients may indicate enhanced oxidative stress within the vascular compartment and, possibly, in other tissues, which may contribute to the proatherogenic state and corresponding organ disturbances in GH-deficient patients, independently from conventional risk factors.

Molecular analysis of the RET and NTRK1 gene rearrangements in papillary thyroid carcinoma in the Polish population.

Among different genetic factors involved in the pathogenesis of the papillary thyroid carcinoma (PTC), rearrangements of RET protooncogene (RET/PTC), as well as rearrangements of NTRK1 protooncogene are best known. The resulting hybrid oncogenes are found in PTCs with variable frequency, depending on the examined population. The relationship between these chromosomal aberrations and clinical outcome of PTCs remains still controversial. The study aimed at estimating the frequency of rearrangements of RET and/or NTRK1 protooncogenes in PTC in the Polish population, and at evaluating the possible relationships between the presence of RET and/or NTRK1 oncogenes and such parameters, as patient's age, gender, histopathological variant of tumor and clinical staging. Expression analysis of RET and NTRK1 was performed by duplex reverse transcription-polymerase chain reaction (duplex RT-PCR) and OneStep RT-PCR, respectively, in tumor tissues obtained from 33 patients with PTC. Rearrangements of the RET protooncogene (RET/PTC1, RET/PTC2 and RET/PTC3) were detected in 7 out of 33 PTC (21%), and rearrangements of NTRK1 [Trk-T1 and Trk(TPM3)] were detected in 4 out of 33 examined samples (12%). In none of the examined cases, did the RET and NTRK1 rearrangements occur in the same sample. No correlations were found between RET/PTC or Trk oncogenic sequences and patient's age, gender, the histopathological variant of PTC and the assignment to particular stage in clinical staging systems (TNM Staging, the University of Chicago clinical class, and Ohio State University Staging). Our study is the first one in which the frequency of NTRK1 rearrangements in PTC was reported for the Polish population. On the other hand, the frequency of RET rearrangements in PTC, as found by us, was similar to the previously reported results for the Polish population. Our results do not confirm the relationship between the structural aberrations in question and the clinical outcome of PTC.

Protective effects of melatonin and indole-3-propionic acid against lipid peroxidation, caused by potassium bromate in the rat kidney.

Potassium bromate (KBrO(3)) is classified as a carcinogenic agent. KBrO(3) induces tumors and pro-oxidative effects in kidneys. Melatonin is a well known antioxidant and free radical scavenger. Indole-3-propionic acid (IPA), an indole substance, also reveals antioxidative properties. Recently, some antioxidative effects of propylthiouracil (PTU)-an antithyroid drug-have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the kidneys and blood serum and, additionally, in the livers and the lungs, collected from rats, pretreated with KBrO(3). Male Wistar rats were administered KBrO(3) (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). The level of lipid peroxidation products-malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA)-was measured spectrophotometrically in thyroid homogenates. KBrO(3), when injected to rats, significantly increased lipid peroxidation in the kidney homogenates and blood serum, but not in the liver and the lung homogenates. Co-treatment with either melatonin or with IPA, but not with PTU, decreased KBrO(3)-induced oxidative damage to lipids in the rat kidneys and serum. In conclusion, melatonin and IPA, which prevent KBrO(3)-induced lipid peroxidation in rat kidneys, may be of great value as protective agents under conditions of exposure to KBrO(3).

Increased expression of mRNA specific for thymidine kinase, deoxycytidine kinase or thymidine phosphorylase in human papillary thyroid carcinoma.

The aim of the present study was to estimate the expression of mRNA, specific for thymidine kinase 1 (TK1), deoxycytidine kinase (dCK), and thymidine phosphorylase (dThdPase), i.e. enzymes involved in pyrimidine and purine metabolism in human papillary thyroid carcinoma (PTC) tissue. Additionally, the expression of dCK was estimated, in medullary thyroid carcinoma (MTC). For control, the RNA expression levels for all the enzymes were measured in macroscopically unchanged thyroid tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) and densitometry were employed for mRNA expression measurements, with the beta-actin gene as a control housekeeping gene. The levels of mRNA expression for TK1, dCK and dThdPase in human PTC, as well as mRNA expression for dCK in MTC, were significantly higher than mRNA expressions for those enzymes found in macroscopically unchanged thyroid tissue. It is concluded that an increased expression of mRNA, specific for TK1, dCK and dThdPase, may be involved in carcinogenic processes in the human thyroid.

Comparison of potential protective effects of melatonin, indole-3-propionic acid, and propylthiouracil against lipid peroxidation caused by potassium bromate in the thyroid gland.

Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid tumors. Melatonin and indole-3-propionic acid (IPA) are effective antioxidants. Some antioxidative effects of propylthiouracil (PTU)--a thyrostatic drug--have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the thyroids, collected from rats treated with KBrO3, and in homogenates of porcine thyroids, incubated in the presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). Homogenates of porcine thyroids were incubated for 30 min in the presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA + 4-HDA) was measured spectrophotometrically in thyroid homogenates. In vivo pretreatment with either melatonin or with IPA or with PTU decreased lipid peroxidation caused by KBrO3--injections in rat thyroid gland. Under in vitro conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced KBrO3-related lipid peroxidation in the homogenates of porcine thyroids. In conclusion, melatonin and IPA may be of great value as protective agents under conditions of exposure to KBrO3.

Increased thymidine kinase activity in human thyroid toxic adenomas: effects of exposure to epidermal growth factor in vitro.

UNLABELLED: The activity of thymidine kinase (TK-EC 2.7.1.21)--an enzyme functioning as a part of the pyrimidine salvage pathway of DNA synthesis--is closely related to growth processes. The aim of the study was to measure TK activity in homogenates of human thyroid tissue of the following types: non-toxic nodular goiter (NTNG)--macroscopically unchanged tissue, non-toxic adenoma (NTA), and toxic adenoma (TA) (obtained from patients, who--before the surgery--had been treated with thyrostatic drugs for thyrotoxicosis). Thyroid tissue was obtained from female patients subjected to subtotal thyroidectomy at the Department of Endocrine Surgery, Medical University of Lódz. Thyroid homogenates were incubated in the presence of epidermal growth factor (EGF), used in five different concentrations (0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml). TK activity was estimated by chromatographic measurements of the amount of the main reaction product--deoxythymidine monophosphate. RESULTS: 1) We did not observe any significant difference between TK activity in the homogenates of the thyroid tissue collected from NTNG and NTA; TK activity was clearly higher in the homogenates of adenomatous tissue, collected from the patients with TA; 2) EGF increased TK activity in the homogenates of the macroscopically unchanged tissue, collected--during surgery--from the patients with NTNG, as well as in homogenates of thyroid tissue from NTA; 3) In case of hyperactive thyroid tissue, obtained from TA, EGF tended to increase TK activity, however, without any statistical differences. Our results confirm TK increased activity in hyperactive thyroid tissue. At the same time, the obtained data suggest a certain role of EGF in goiter formation in humans.

The role of oxidative stress in physiological and pathological processes in the thyroid gland; possible involvement in pineal-thyroid interactions.

Reactive oxygen species (ROS) play an important role in physiological processes, but - when being in excess - ROS cause oxidative damage to molecules. Under physiological conditions, the production and detoxification of ROS are more-or-less balanced. Also in the thyroid, ROS and free radicals participate in physiological and pathological processes in the gland. For example, hydrogen peroxide (H2O2) is crucial for thyroid hormone biosynthesis, acting at different steps of the process. Additionally, H2O2 is believed to participate in the Wolff-Chaikoff's effect, undergoing in conditions of iodide excess in the thyroid. Much evidence has been accumulated indicating that oxidative stress is involved in pathomechanism of thyroid disease, e.g., Graves' disease, goiter formation or thyroid cancer. Melatonin (N-acetyl-5-methoxytryptamine) - the main secretory product of the pineal gland - is a well-known antioxidant and free radical scavenger, widely distributed in the organism. Mutual relationships between the pineal gland and the thyroid have - for a long time - been a subject of intensive research. The abundant to-date's evidence relates mostly to the inhibitory action of melatonin on the thyroid growth and function and - to a lesser extent - to the stimulatory effects of thyroid hormones on the pineal gland. It is highly probable that under physiological conditions melatonin and, possibly, other antioxidants regulate ROS generation for thyroid hormone synthesis. We believe that melatonin may protect against extensive oxidative damage in the course of certain thyroid disorders or in case of a harmful action of some external factors on the thyroid. Thus, oxidative damage and the protective action of antioxidants, melatonin included, may occur during both physiological and pathological processes in the thyroid, however, this assumption, requires further studies.

Melatonin reduces Fenton reaction-induced lipid peroxidation in porcine thyroid tissue.

Free radicals and reactive oxygen species (ROS) participate in physiological and pathological processes in the thyroid gland. Bivalent iron cation (ferrous, Fe(2+)), which initiates the Fenton reaction (Fe(2+) + H2O2 --> Fe(3+) + *OH + OH(-)) is frequently used to experimentally induce oxidative damage, including that caused by lipid peroxidation. Lipid peroxidation is involved in DNA damage, thus indirectly participating in the early steps of carcinogenesis. In turn, melatonin is a well-known antioxidant and free radical scavenger. The aim of the study was to estimate the effect of melatonin on basal and iron-induced lipid peroxidation in homogenates of the porcine thyroid gland. In order to determine the effect of melatonin on the auto-oxidation of lipids, thyroid homogenates were incubated in the presence of that indoleamine in concentrations of 0.0, 0.00001, 0.0001, 0.001, 0.01, 0.1, 0.25, 0.5, 1.0, 2.5, or 5.0 mM. To study melatonin effects on iron-induced lipid peroxidation, the homogenates were incubated in the presence of FeSO(4) (40 microM) plus H2O2 (0.5 mM), and, additionally, in the presence of melatonin in the same concentrations as above. The degree of lipid peroxidation was expressed as the concentration of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) per mg protein. Melatonin, in a concentration-dependent manner, decreased lipid peroxidation induced by Fenton reaction, without affecting the basal MDA + 4-HDA levels. In conclusion, melatonin protects against iron + H2O2-induced peroxidation of lipids in the porcine thyroid. Thus, the indoleamine would be expected to prevent pathological processes related to oxidative damage in the thyroid, cancer initiation included.

Expression of genes for certain enzymes of pyrimidine and purine salvage pathway in peripheral blood leukocytes collected from patients with Graves' or Hashimoto's disease.

Increased activities of some enzymes, which participate in pyrimidine and purine salvage pathway, were found in blood fractions of patients suffering from different autoimmunological diseases, thyroid diseases included. The aim of the study was to estimate the expression of genes, specific for deoxycytidine kinase (dCK, EC 3.7.1.74), thymidine kinase 1 (TK1; EC 2.7.1.21), and adenosine deaminase (ADA, EC 3.5.4.4) in blood leukocytes, collected from patients with autoimmunological thyroid diseases (AITD), i.e., Graves' or Hashimoto's disease. The total mRNA was isolated from peripheral blood leukocytes and, afterwards, submitted to reverse transcription (RT), with the following amplification of genes encoding for particular examined enzymes and beta-actin, as a supervisory gene [RT-polymerase chain reaction (RT-PCR)]; ADA gene was amplified with the use of three different primer pairs (ADA3, ADA4, and ADA5). PCR products were electrophoresed in 8% polyacrylamide gel and then, submitted to densitometric analysis. The levels of expression of all the examined genes in leukocytes from patients with either Graves' or Hashimoto's disease were significantly increased when compared to those in controls; above a twofold elevation of expression of TK1, ADA4, and ADA5 genes was observed. In conclusion, the changes of activities of salvage enzymes in patients with AITD occur likely at transcription level; the measurement of gene expression for purine and pyrimidyne salvage enzymes may likely help explain the mechanism of autoimmune diseases, being also significant in the diagnostics and/or monitoring of AITD.

Purine metabolism in leukocytes and erythrocytes in Graves' or Hashimoto's disease.

INTRODUCTION: Adenosine deaminase (ADA), purine nucleoside phosphorylase (PNPase), S-adenosylhomocysteine hydrolase (SAHH), 5'-nucleotidase (5N), and deoxycytidine kinase (dCK) are involved in purine salvage metabolism. Changes of the activities of the above enzymes have been observed in blood cells in patients with immunological disorders. MATERIALS AND METHODS: The activities of ADA, PNPase, SAHH, 5'N, and dCK in lysates of leukocytes and erythrocytes, obtained from patients with Graves' or Hashimoto's disease, were measured, using chromatographic analysis. Serum concentrations of antithyroglobulin (Tg Ab) and antithyroperoxidase (TPO Ab) antibodies were measured by an immunoenzymatic method. RESULTS: (1) ADA activity in leukocytes, obtained from patients with Hashimoto's disease, was significantly higher than in control leukocytes, as well as in leukocytes from patients with Graves' disease; (2) dCK activities in leukocytes from patients with both Graves' and Hashimoto's diseases were approximately four and five times higher, respectively, than in leukocytes of control subjects; (3) a positive correlation was observed between dCK activity in leukocytes and serum Tg Ab concentration in patients with Graves' disease. In conclusion, the increased ADA and dCK activities in leukocytes from patients with Graves' and Hashimoto's diseases may be regarded as indicators of autoimmunological thyroid diseases.

Inhibitory effect of melatonin on homocysteine-induced lipid peroxidation in rat brain homogenates.

Oxidative damage is implicated in several pathologies including cardiovascular disease. As a model system to study the response of cells to oxidative insults, homocysteine toxicity was examined since it is an independent risk factor for atherosclerotic disease. The levels of malondialdehyde and 4-hydroxyalkenals were assayed as an index of oxidatively damaged lipid. In in vitro experiments, the increase of lipid peroxidation products induced by homocysteine were concentration- and time-dependent. To study the protective effect of melatonin on homocystine induced lipid peroxidation, brain homogenates were treated with different concentrations of melatonin. The accumulation of malondialdehyde and 4-hydroxyalkenals induced by homocysteine was significantly reduced by melatonin in a concentration-dependent manner. Additionally, a melatonin concentration of 1.5 mM reduced the levels of oxidatively damaged lipid products below those measured in control homogenates (no homocysteine, no melatonin). These data suggest that melatonin, an endogenous antioxidant may have a role in protecting cells from oxidative damage due to homocysteine and they support the idea that pharmacological concentrations could be used as a therapeutic agent in reducing cardiovascular disease where homocysteine may be a causative or contributing agent.

Potential anticarcinogenic action of melatonin and other antioxidants mediated by antioxidative mechanisms.

The complex process of carcinogenesis is, to a large extent, due to oxidative stress. Numerous indicators of oxidative damage are enhanced in the result of the action of carcinogens. Several antioxidants protect, with different efficacy, against oxidative abuse, exerted by carcinogens. Recently, melatonin (N-acetyl-5-methoxytryptamine) and some other indoleamines have gained particular meaning in the defense against oxidative stress and, consequently, carcinogenesis. Some antioxidants, like ascorbic acid, play a bivalent role in the antioxidative defense, revealing, under specific conditions, prooxidative effects. Among known antioxidants, melatonin is particularly frequently applied in experimental models of anticarcinogenic action. In the numerous studies, examining several parameters of oxidative damage and using several in vitro and in vivo models, this indoleamine has been shown to protect DNA and cellular membranes from the oxidative abuse caused by carcinogens. When either preventing or decreasing the oxidative damage to macromolecules, melatonin also protects against the initiation of cancer. The protection provided by melatonin and some other antioxidants against cellular damage, due to carcinogens, make them potential therapeutic supplements in the conditions of increased cancer risk.

REVIEW. Melatonin and the thyroid gland.

This review briefly summarizes the published data on relationships observed between melatonin - the main pineal hormone, and the thyroid gland. The prevailing part of the survey is devoted to thyroid growth processes and function. A large experimental evidence exists suggesting the inhibitory action of melatonin on thyroid growth and function; this effect has been revealed by using different experimental models: by chronic and short-term melatonin administration in vivo, by light restriction, which is known to increase the activity of the pineal gland, by pinealectomy, etc., as well as by employing the in vitro conditions. Thus, much information has been accumulated, indicating - in experimental conditions - a mutual relationship between the pineal gland and the thyroid. The confirmation of these relations in clinical studies in humans meets numerous difficulties, resulting - among others - from the fact that, nowadays, human beings, as well as certain animal species, used in experimental studies, have been living far away from their natural and original habitat. It makes almost impossible to compare the results obtained in particular studies performed in different species, on the pineal-thyroid interrelationship.

Causes of oxidative stress in the pre- and perinatal period.

Oxidative stress may be defined as an imbalance between pro-oxidant and antioxidant forces resulting in an overall pro-oxidant insult. Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, augmented levels of oxidative stress would be expected. Arguments for a role of oxidative stress/oxidative lipid derivatives in the pathogenesis of preeclampsia are documented in many papers and evidence continues to accumulate that oxidative stress is a mediator of endothelial dysfunction and thus contributes to the cardiovascular complications of preeclampsia. Also other conditions, such as toxic substance exposure, smoking and asphyxia likewise induce oxidative stress. The oxidized lipid products generated as a consequence of these conditions are highly reactive and cause damage to cells and cell membranes. Thus, increased oxidative stress accompanied by reduced endogenous defences may play a role in the pathogenesis of a number of diseases in the newborn.

Melatonin protects against oxidative stress caused by delta-aminolevulinic acid: implications for cancer reduction.

delta-Aminolevulinic acid (ALA) is a precursor of haem. The increased concentration of ALA is typically related to acute intermittent porphyria, hereditary tyrosinemia, and lead poisoning. delta-Aminolevulinic acid produced in excess accumulates in a number of organs, causes oxidative damage, and often leads to cancer. Melatonin (N-acetyl-5-methoxytryptamine) is a well-known antioxidant, free radical scavenger, and exhibits anticarcinogenic properties. It protects DNA, lipids, and proteins from oxidative damage. The protective effects of melatonin against ALA-induced oxidation of guanine bases, lipid peroxidation, and alterations in membrane fluidity in several organs have been documented. There is an inverse relationship between melatonin and ALA concentrations in both experimental and clinical conditions of porphyria. The marked efficacy of melatonin in protecting against ALA-related oxidative stress, its oncostatic properties, and low toxicity constitute reasons to consider the use of this indoleamine as a co-treatment in patients suffering from disturbances related to ALA accumulation.

Thymidine kinase and adenosine kinase activities in homogenates of thyroid lobes in hemithyroidectomized rats; effects of melatonin in vitro.

OBJECTIVES: Thymidine kinase (TK, EC 2.7.1.21) is a part of the pyrimidine salvage pathway, involved in DNA synthesis. In turn, adenosine kinase (AK, EC 2.7.1.20) functions as a part of the purine metabolic pathway, involved in DNA synthesis. Melatonin (Mel) is an indoleamine which is known to inhibit growth processes in the thyroid gland and also in other endocrine and non-endocrine tissues. The aim of our study was to examine TK and AK activities in homogenates of the rat thyroid lobes remaining after contralateral hemithyroidectomy (hemiTx); additionally, incubations with Mel (10(-6), 10(-9), and 10(-12) M) were performed. METHODS: The experiment was performed on young male Wistar rats (6-week old). The enzyme activities were measured by ascending chromatography and expressed as the amounts of radioactive reaction products of the phosphorylation of dThd (for TK) and of dAdo (for AK). RESULTS: 1. HemiTx increased TK activity in homogenates of the remaining thyroid lobe; 2. Mel increased TK activity in all the groups (intact, sham-operated- and hemiTx-rats), except for the concentrations of 10(-9) and 10(-12) M in the hemiTx-rats, in which the increasing effects of Mel on TK activity reached the borderline statistical significance only; 3. Mel increased the AK activity in intact and in shamTx animals; 4. No statistically significant changes were found in AK activity following Mel in vitro in the incubated remaining thyroid lobes, collected from hemiTx-rats.

Melatonin suppresses autoxidation and hydrogen peroxide-induced lipid peroxidation in monkey brain homogenate.

OBJECTIVES: Melatonin, the major secretory product of the pineal gland, is known as an effective antioxidant and neuroprotector. Its neuroprotective actions and mechanisms have been documented in a variety of rodent brain models. However, little is known of melatonin's antioxidative capacity in the brain of primates. Herein, we investigated whether melatonin would suppress autoxidation and exogenous hydrogen peroxide-induced lipid peroxidation in monkey cerebral cortical homogenates. MATERIALS AND METHODS: The monkey brain was dissected during routine autopsy and immediately frozen at -80 degrees C until the experiment. A sample of cerebral cortex (50 mg) was homogenized in 1 ml ice cold phosphate buffer (20 mM, pH 7.4) at 0-4 degrees C. Four different treatments of cerebral cortical homogenates were performed: 1) homogenates incubated in a water bath at different temperatures (4 degrees C, 25 degrees C or 37 degrees C, respectively) for two hours to induce autoxidation; 2) homogenates co-incubated with different concentrations of melatonin at 37 degrees C for 2 hours; 3) homogenates co-incubated with 1 mM vitamin C and different concentrations of hydrogen peroxide at 37 degrees C for 1 hour to induce membrane lipid peroxidation; 4) homogenates incubated with different concentrations of melatonin and 1 mM H2O2 plus 1 mM vitamin C. After incubation, homogenates were analyzed for products of lipid peroxidation (malondialdehyde and 4-hydroxy-alkenals). RESULTS: The levels of lipid peroxidation products significantly increased in monkey cerebral cortical homogenates as a consequence of autoxidation or after the addition of H2O2 plus vitamin C. Melatonin not only suppressed the increase in lipid peroxidation induced by H2O2 plus vitamin C but also inhibited lipid breakdown resulting from autoxidation. The concentrations of melatonin required to suppress lipid peroxidation resulting from autoxidation or induced by exogenous oxidants in monkey cerebral cortical homogenates were in the same dose range. CONCLUSION: The results show for the first time that melatonin functions as an antioxidant and neuroprotector in primate brain tissue as was observed previously in rodent brain. The data provide information supporting the use of melatonin in the treatment of neurodegenerative disorders that involve oxidative damage to brain lipids.

Pyrimidine and purine salvage deoxyribonucleoside metabolism in hepatic and renal homogenates from rats pretreated with propylthiouracil or L-thyroxine.

OBJECTIVES: In vitro activities of thymidine kinase (TK, EC 2.7.1.21), adenosine kinase (AK, EC 2.7.1.20) and deoxycytidine kinase (dCK, EC 2.7.1.74) enzymes involved in the salvage pathway of DNA precursor synthesis, in homogenates of the rat liver and kidney, were examined. Type I iodothyronine-5'-deiodinase (5'D-I) is the main enzyme responsible for peripheral metabolism of thyroid hormones. This occurs especially in the liver, kidney and muscle. The activity of 5'D-I is inhibited bypropylthiouracil (PTU), an antithyroid drug. METHODS: The liver and kidney were collected from rats pretreated in vivo with either a 0.1% solution of PTU in drinking water for 2 weeks or injected with levothyroxine (L-T(4), 50 &mgr;g/kg BW, daily) for 2 weeks. The enzyme activities were measured by ascending chromatography and expressed asthe amounts of radioactive reaction products of the phosphorylation of dThd (for TK), ofdAdo (for AK and dCK) and of dGuo (for dCK). RESULTS: In liver homogenates, PTU-pretreatment decreased the activities of the three enzymes when compared to control values and those of L-T(4)-treated animals; also L-T(4) injections decreased the AK and dCK activities in the liver homogenates. PTU-pretreatment increased TK activity and the rate of dGuo phosphorylation in kidney homogenates, when compared to controls and to the L-T(4)-pretreated animals. Conversely, both PTU- and L-T(4)-pretreatment reduced the rate of dAdo phosphorylation in kidney homogenates. CONCLUSION: Changes in the activities of examined enzymes which participate inpyrimidine orpurine metabolism of the salvage pathway of DNA synthesis in the liver afterPTU-pretreatment (as shown herein) are similar to the changes of the 5'D-I activity after PTU-treatment (as reported by others). Thus, the observations suggest a role of the salvage pathway of DNA synthesis in the peripheral metabolism of thyroid hormones.