Selenoprotein P, peroxiredoxin-5, renalase, and total antioxidant status in patients with suspected obstructive sleep apnea.

PURPOSE: The aim of this study was to investigate the relationship between selenoprotein P, peroxiredoxin-5, renalase, total antioxidant status (TAS), mean blood pressure (mBP), and apnea-hypopnea index (AHI). METHODS: The study group consisted of 112 patients hospitalized to verify the diagnosis of obstructive sleep apnea (OSA). The inclusion criteria were consent to participate in the study and age ≥ 18 years. Patients with active proliferative disease, severe systemic diseases, or mental diseases were excluded from the study. Each patient underwent full polysomnography and had blood pressure measured. Blood samples were collected and laboratory test was performed. RESULTS: Among 112 patients enrolled, there was a statistically significant negative linear correlation between blood pressure values (sBP, dBP, mBP) and selenoprotein P, renalase, and TAS levels. Similarly, there was a negative linear correlation between AHI and selenoprotein P, renalase, and TAS levels, but none between AHI and peroxiredoxin-5. Based on the obtained regression models, higher selenoprotein P, peroxiredoxin-5, and renalase levels were independently associated with higher TAS. Lower mBP values were independently associated with the use of antihypertensive drugs, higher TAS, and younger age. Male gender, higher BMI, and higher mBP were independently associated with higher AHI. CONCLUSIONS: Higher concentrations of selenoprotein P, peroxiredoxin-5, and renalase were associated with higher TAS, which confirms their antioxidant properties. There was an indirect connection between tested antioxidants and blood pressure values.

Selenoprotein P, Peroxiredoxin-5, Renalase and Selected Cardiovascular Consequences Tested in Ambulatory Blood Pressure Monitoring and Echocardiography.

This study aimed to assess the relationship between chosen antioxidants, namely selenoprotein P (SELENOP), peroxiredoxin-5 (Prdx-5), renalase and selected cardiovascular consequences tested in ambulatory blood pressure monitoring (ABPM) and echocardiography (ECHO). In our work, cardiovascular consequences refer to higher mean blood pressure (MBP) and pulse pressure (PP) on ABPM, as well as to left atrial enlargement (LAE), left ventricular hypertrophy (LVH) and lower left ventricular ejection fraction (LVEF%) on ECHO. The study group consisted of 101 consecutive patients admitted to the Department of Internal Medicine, Occupational Diseases and Hypertension to verify the diagnosis of Obstructive Sleep Apnoea (OSA). Each patient underwent full polysomnography, blood tests, ABPM and ECHO. Both selenoprotein-P and renalase levels correlated with different ABPM and ECHO parameters. We found no correlation between the peroxiredoxin-5 level and none of the tested parameters. We point to the possible application of SELENOP plasma-level testing in the initial selection of high cardiovascular-risk patients, especially if access to more advanced examinations is limited. We further suggest SELENOP measurement as a possible indicator of patients at increased left ventricular hypertrophy risk who should be of particular interest and may benefit from ECHO testing.

Association Between Serum Selenium Concentration and OPG/RANKL/RANK Axis in Patients with Arterial Hypertension.

The aim of the study was to determine the relationship between the serum selenium concentration (Se-S) and the blood concentrations of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL) and the OPG/RANKL ratio in patients with arterial hypertension. The study group comprised 138 patients with arterial hypertension (age: 56.04 ± 11.59 years). Se-S was determined in all the subjects. Based on the Se-S, the following subgroups were distinguished: a subgroup of patients with a lower Se-S ("low-Se", Se-S < median) and a subgroup of patients with a higher Se-S ("high-Se", Se-S ≥ median). Moreover, the blood concentrations of the parameters of bone metabolism and extraskeletal calcification were assessed: OPG and RANKL. The OPG/RANKL ratio was calculated. In the "low-Se" subgroup, the RANKL concentration was statistically significantly lower, and the OPG/RANKL ratio was statistically significantly higher than in the patients in the "high-Se" subgroup. The correlation analysis showed the negative linear relationships between Se-S and OPG (r = - 0.25, p < 0.05) and between Se-S and OPG/RANKL (r = - 0.47, p < 0.05). Moreover, Se-S positively correlated with RANKL (r = 0.33, p < 0.05). In regression analysis, higher body mass index (BMI), smoking and lower Se-S were independently associated with a higher OPG/RANKL ratio, while lower BMI, use of diuretics, ß-blockers and ACE inhibitors and lower OPG/RANKL ratio with effective blood pressure control. In summary, in the group of patients with arterial hypertension, lower Se-S is associated with an unfavourable prognostic panel of parameters of bone metabolism and extraskeletal calcification. Lower Se-S is an independent risk factor for a higher OPG/RANKL ratio, which is an independent prediction factor of ineffective blood pressure control in patients with hypertension.

The Total Antioxidant Status, Serum Selenium Concentrations and the Ultrasound Assessment Carotid Intima Media Thickness in Patients with Arterial Hypertension.

The objective of the study was to establish the correlation between serum selenium concentrations, total antioxidant status, and the carotid intima media thickness in ultrasound assessment in patients with arterial hypertension. A group of 76 people suffering from arterial hypertension was qualified to participate in the study. The mean age of the respondents was 53.48 ± 12.78. Serum selenium concentrations (Se-S) and total antioxidant status (TAS) were determined in all respondents. Se-S were determined by hydride generation atomic absorption spectroscopy (HGAAS). The antioxidant status was assessed by the enzyme-linked immunosorbent assay (ELISA). In addition, an ultrasound exam of the carotid arteries was performed, and the intima media thickness (cIMT) was measured. In the study group, Se-S and TAS were 89.73 ± 18.99 µg/L and 1.18 ± 0.35 mM. However, the cIMT measured using ultrasound was 0.68 ± 0.15 mm. cIMT was significantly greater in patients with arterial hypertension with Se-S < median in comparison to patients with arterial hypertension with Se-S ≥ median (0.73 ± 0.19 mm vs. 0.65 ± 0.10 mm, p < 0.05), as well as in patients with arterial hypertension with TAS < median than in patients with arterial hypertension with TAS ≥ median (0.79 ± 0.18 mm vs. 0.56 ± 0.13 mm, p < 0.05). In regression analysis, older age, higher BMI, smoking, and lower serum selenium concentrations were independently correlated with the greater cIMT. Higher BMI and smoking were independent risk factors for the lower TAS, and the use of ACE inhibitors, ß-blockers, and higher Se-S were independent factors of protection against the lower TAS. In patients with arterial hypertension, the lower total antioxidant status due to lower serum selenium concentrations may be correlated with an increase of the carotid intima media thickness measured using ultrasound.

Renalase and hypertension-demographic and clinical correlates in obstructive sleep apnea.

BACKGROUND: Renalase plays an important role in blood pressure regulation. Obstructive sleep apnea (OSA) is a common respiratory disorder associated with hypertension and cardiovascular complications. The aim of the study was to assess the relationship between sleep apnea and renalase concentration. MATERIAL AND METHODS: Adult patients (n = 113) were evaluated for OSA in a sleep laboratory using polysomnography. The respiratory events were scored according to the standards developed by the American Academy of Sleep Medicine. The blood renalase concentration was determined by the ELISA (enzyme-linked immunosorbent assay) test. RESULTS: OSA (AHI ≥ 5) was diagnosed in 71% (n = 80) of the studied population. Renalase concentration was statistically significantly lower in the group with moderate-to-severe OSA (AHI ≥ 15) compared with the group without OSA (AHI < 5) (139.56 ± 175.72 ng/ml vs. 230.97 ± 240.50 ng/ml, p = 0.042). We have found statistically significant negative correlation between renalase and AHI in hypertensives, but not in normotensives. The statistically significant negative correlation was observed between AHI and renalase in the whole studied group, in males, and in the group of age < 60 years old. There was not such a correlation in females and in the group > 60 years old. Based on the regression model, it was shown that lower renalase concentration, hypertension, higher BMI, and male gender are independently associated with higher AHI. CONCLUSIONS: There is a relationship between the blood renalase concentration and the severity of OSA, which may influence hypertension development in OSA.

Total antioxidant status reduction conditioned by a serum selenium concentration decrease as a mechanism of the ultrasonographically measured brachial artery dilatation impairment in patients with arterial hypertension.

The objective of the study was to determine the relationship between serum concentrations of selenium (SeS) and zinc (ZnS), total antioxidant status (TAS) and endothelial function assessed by ultrasonographic method of dilatation of the brachial artery in 141 hypertensive patients. Patients with SeS < median were characterized by a statistically significantly lower flow-mediated dilation (FMD) than patients with SeS ≥ median. Patients with TAS < median were characterized by a significantly lower FMD than patients with TAS ≥ median. Older age, higher BMI, male gender, higher blood total cholesterol, ischemic heart disease, smoking and lower SeS constitute independent predictors of inferior endothelial function, expressed in lower FMD values. Smoking is an independent predictor of lower TAS, and the use of ß-blockers and higher serum selenium levels are independent predictors of higher TAS. In summary, a decrease in TAS should be considered as a mechanism of inferior endothelial function in hypertensive patients conditioned by a decrease in SeS.

The Relationship between Sleep Bruxism Intensity and Renalase Concentration-An Enzyme Involved in Hypertension Development.

BACKGROUND AND OBJECTIVES: Renalase, a novel amine oxidase, is involved in the development of hypertension. Sleep bruxism (SB) is a sleep-related behavior characterized by rhythmic or non-rhythmic activity of the masticatory muscles, which leads to the mechanical wear of teeth, pain in the masticatory muscles, and disturbed sleep. Recent studies indicate that SB plays a role in increased blood pressure. Therefore, this study aimed to determine the relationship between sleep bruxism intensity and renalase concentration, which may help in the future to elucidate the pathogenesis of hypertension and other cardiovascular disorders. MATERIAL AND METHODS: SB was evaluated in 87 adult patients using single-night diagnostic polysomnography with video and audio recordings, and the episodes of bruxism were scored according to the standards of the American Academy of Sleep Medicine. The levels of serum renalase were measured in the patients using enzyme-linked immunosorbent assay kits. RESULTS: SB (Bruxism Episode Index (BEI) ≥2) was diagnosed in 54% (n = 47) of the studied population, and the mean concentration of renalase was found to be decreased in the hypertensive group compared with the normotensive group (133.33 ± 160.71 vs 219.23 ± 220.58, p = 0.047). In addition, a linear negative correlation was observed between the renalase concentration and the body mass index (BMI) in the SB group (r = 0.38, p < 0.05) but not in controls. Thus, higher BEI and higher BMI were identified as factors independently associated with the lower concentration of renalase, but only in the group of patients which had a blood renalase concentration of >212.5 ng/mL. CONCLUSION: There exists an association between renalase concentration and SB intensity, and further studies are needed to clarify the role of renalase in the pathogenesis of hypertension and other cardiovascular disorders.

Alleviating Effect of α-Lipoic Acid and Magnesium on Cadmium-Induced Inflammatory Processes, Oxidative Stress and Bone Metabolism Disorders in Wistar Rats.

Cadmium exposure contributes to internal organ dysfunction and the development of chronic diseases. The aim of the study was to assess the alleviating effect of α-lipoic acid and/or magnesium on cadmium-induced oxidative stress and disorders in bone metabolism, kidney and liver function, and hematological and biochemical parameters changes. Male rats were exposed to cadmium (30 mg Cd/kg of feed) for three months. Some animals exposed to Cd were supplemented with magnesium (150 mg Mg/kg of feed) and/or with α-lipoic acid (100 mg/kg body weight, four times a week). Cd intake inhibited body weight gain and lowered hemoglobin concentration, whereas it increased the activities of liver enzymes, as well as the level of oxidative stress, CTX-1 (C-terminal telopeptide of type I collagen, bone resorption marker), and CRP (C-reactive protein, marker of inflammation); it decreased vitamin D3, GSH (reduced glutathione), and the serum urea nitrogen/creatinine index. Mg and/or α-lipoic acid supplementation increased the antioxidant potential, and partially normalized the studied biochemical parameters. The obtained results show that both magnesium and α-lipoic acid decrease oxidative stress and the level of inflammatory marker, as well as normalize bone metabolism and liver and kidney function. Combined intake of α-lipoic acid and magnesium results in reinforcement of the protective effect; especially, it increases antioxidant defense.

Influence of physical training on markers of bone turnover, mechanical properties, morphological alterations, density and mineral contents in the femur of rats exposed to cadmium and/or alcohol.

The aim of the study was to investigate the effect of physical training on bone parameters of rats exposed to alcohol (Al) and/or cadmium (Cd). Young female rats were divided into one control group and six groups exposed to Cd and/or Al. Al (36% calories of diet) and Cd (20 mg Cd/kg feed) were administered with liquid diet. Half of the rats from the treated groups were subjected to treadmill training (20 m/min for 0.5 h, 4 days a week). The experiment was carried out for 5 months. Al decreased the concentration of calcium (Ca) and iron (Fe) in the femur, whereas Cd and Cd + Al intake reduced the contents of Ca, Fe and zinc. Al and/or Cd caused an increase in both C-terminal telopeptide of type I collagen (CTX1; bone resorption marker) and osteocalcin (OC; formation indicator) and enhanced the degree of porosity and flexural strength of the femur. Al partially prevented the loss of Fe from the bone caused by Cd, but intensified the inhibition of growth of body weight in comparison with separate exposure to Cd. In rats co-exposed to Cd + Al, the levels of CTX1 were greater compared with those treated with Al or Cd separately, and the density was less than that in rats exposed to Al separately. The training caused increases of magnesium and Ca contents, decreases in CTX1, as well as increases in OC and bone density, decreasing their porosity. The effect of training on the bone status, however, was limited (especially in rats co-exposed to Cd and Al) because of the increase in their mineralization, stimulated by exercises, was insufficient in relation to collagen production intensity. In conclusion, training had favourable effects on some bone parameters, but did not compensate for the negative effects of Al and/or Cd exposure on the poor mineralization and histopathological and morphological changes in the femur.

Oxidative damage of DNA in subjects occupationally exposed to lead.

BACKGROUND: Exposure to lead (Pb) in environmental and occupational settings continues to be a serious public health problem and may pose an elevated risk of genetic damage. OBJECTIVES: The aim of this study was to assess the level of oxidative stress and DNA damage in subjects occupationally exposed to lead. MATERIAL AND METHODS: We studied a population of 78 male workers exposed to lead in a lead and zinc smelter and battery recycling plant and 38 men from a control group. Blood lead levels were detected by graphite furnace atomic absorption spectrophotometry and plasma lead levels by inductively coupled plasma-mass spectrometry. The following assays were performed to assess the DNA damage and oxidative stress: comet assay, determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation and total antioxidant status (TAS). RESULTS: The mean concentration of lead in the blood of the exposed group was 392 ± 103 µg/L and was significantly higher than in the control group (30.3 ± 29.4 µg/L, p < 0.0001). Oxidative DNA damages measured by comet assay showed no significant differences between populations. The concentration of 8-OHdG was about twice as high as in the control group. We found a significant positive correlation between the level of biomarkers of lead exposure [lead in blood, lead in plasma, zinc protoporphyrin (ZPP)] and urine concentration of 8-OHdG. The level of oxidative damage of DNA was positively correlated with the level of lipid peroxidation (TBARS) and negatively with total anti-oxidative status (TAS). CONCLUSIONS: Our study suggests that occupational exposure causes an increase in oxidative damage to DNA, even in subjects with relatively short length of service (average length of about 10 years). 8-OHdG concentration in the urine proved to be a sensitive and non-invasive marker of lead induced genotoxic damage.

Serum 8-hydroxy-2-deoxyguanosine as a marker of DNA oxidative damage in horses with recurrent airway obstruction.

BACKGROUND: It has been reported that equine recurrent airway obstruction (RAO) is a state of oxidative stress. Oxidant-antioxidant imbalance is known to increase the conversion of deoxyguanosine to 8-hydroxy-2-deoxyguanosine (8-OHdG) in DNA. 8-OHdG can easily be measured using ELISA tests in serum or urine samples. In this study, we analysed serum 8-OHdG levels in horses with recurrent airway obstruction and in healthy controls. RESULTS: The study material consisted of seven healthy horses and seven horses with symptomatic RAO. All horses were exposed to moldy hay and straw for 48 h to induce clinical exacerbation of RAO. The serum 8-OHdG levels were determined using the ELISA Highly Sensitive 8-OHdG kit. The difference between the levels of 8-OHdG in healthy and RAO-affected horses was significant. The median level of 8-OHdG was 0.044 ng/ml in the healthy controls versus 0.498 ng/ml in RAO horses (P = 0.0021). CONCLUSIONS: The results of the study strongly suggest that DNA damage coexists in the course of equine RAO. We therefore propose that future research should aim at the development of new drugs that target pro-inflammatory molecules, since DNA damage appears to be the result of chronic inflammation.

Effects of chronic exposure to lead, cadmium, and manganese mixtures on oxidative stress in rat liver and heart.

The aim of this study was to assess the effects of chronic combined exposure to low, environmental doses of Cd, Pb, and Mn on oxidative stress in the liver and heart of rats and on their liver function parameters. Male Wistar rats were divided randomly into eight groups. For nine months controls were receiving drinking water alone, whereas the exposed groups were receiving drinking water with Pb (0.2 mg L(-1)), Cd (1 mg L(-1)), and Mn (2 mg L(-1)) alone or in combinations. Malondialdehyde (MDA) significantly increased in both heart and liver of the animals after combined exposure to metals. Heart MDA correlated with blood Cd, Pb, and Mn and liver MDA with blood Cd. Aspartate aminotransferase (AST) activity and bilirubin concentration also increased significantly in the animal group exposed to all three metals and correlated positively with blood Cd, Pb, and Mn. Our study has confirmed the synergistic effect of the Cd, Mn, and Pb combination on the increase in heart MDA. A similar synergy was observed for Pb+Mn in the increase of serum alanine aminotransferase (ALT) activity as an indicator of liver function.

Interaction between blood selenium concentration and a levels of oxidative stress and antioxidative capacity in healthy children.

The study aimed at defining the relationship between blood selenium concentration (Se-B) and levels of oxidative stress and antioxidative capacity in healthy children. The studies were conducted on 337 children (mean age: 8.53±1.92 years). The groups of individuals with Se-B <1st quartile (group I, Se-B<70µg/L), with Se-B fitting the range of 1st quartile and median (group II, Se-B: 70-76.9µg/L), with Se-B between the median and 3rd quartile (group III, Se-B: 77-83.9µg/L) and those with Se-B above the 3rd quartile (group IV, Se-B≥84µg/L) were distinguished. Level of oxidative stress was defined using determination of urine malonyldialdehyde concentration (MDA) and urine 8-hydroxy-2-deoxyguanosine concentration (8-OHdg). Urine total antioxidant status (TAS) was determined. In group IV TAS was significantly higher than in groups I-III. A positive correlation was detected between Se-B and TAS. In healthy children an appropriately high Se-B seems to ensure higher total antioxidative status.

Oxidative stress level in the testes of mice and rats during nickel intoxication.

The genotioxic and carcinogenic effect of nickel probably results from its capacity to produce reactive oxygen species (ROS) and disturb the redox balance. The aim of the study was to find out if rats lacking spermatic protamine 2 are less susceptible to Ni(II) than mice. Consequently, the levels of malondialdehyde + 4 hydroxynonenal (MDA+4HDA) - markers of lipid peroxidation, as well as the level of reduced glutathione (GSH) were measured within the rat and mouse testes. Our results showed that the levels of lipid peroxidation markers were elevated in testicular homogenates of intoxicated mice without any changes in rats. GSH level was lower in the group of intoxicated mice comparing to the control without statistically significant changes in rats' homogenates. Moreover, the level of GSH in the testes of intoxicated mice was lower than in rats. On the basis of our results, it appears that Ni(II) can initiate oxidative stress in the testes of mice but not of rats and can reduce GSH level. Consequently, the antioxidative defense of the testes is reduced. Ni(II) that causes oxidative stress in the testes may also contribute to infertility.

The influence of road transport on the activities of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase in equine erythrocytes.

BACKGROUND: Transport of horses may have significant impact on serum biochemical and hematologic analytes and resistance to infection. OBJECTIVE: The aim of our study was to assess the influence of transport stress on selected enzymatic antioxidants in equine blood. METHODS: The study was conducted on a group of 60 horses of different breeds and ranging in age from 4 to 10 years. Venous blood was collected immediately before loading horses onto trailers for 8 hours of transport (I), immediately after unloading them from the trailer (II), and after subsequent stall rest for 24 hours (III). Hemolysates of blood were prepared, and hemoglobin (Hb) concentration and activities of the enzymatic antioxidants glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) were measured. Enzyme activities were expressed as units of activity per gram of hemoglobin. RESULTS: There were significant decreases in activities (mean ± SD U/g Hb [minimum-maximum]) of GPx between collection times I (36 ± 14 U/g Hb [9-67 U/g Hb]) and III (30 ± 11 U/g Hb [12-51 U/g Hb]) and of GR between collection times I (54 ± 28 U/g Hb [7-117 U/g Hb]) and II (40 ± 23 U/g Hb [12-145 U/g Hb]). There was no significant difference in activities of GR between collection times I and III (50 ± 27 U/g Hb [9-116 U/g Hb]). There were no differences detected in GST activity among the 3 collection times. CONCLUSION: Road transport has an impact on activities of the antioxidant enzymes GPx and GR, with recovery of GR activity evident by 24 hours post-transport. Decreased activity of these enzymes may be one mechanism for increased susceptibility to infections that are manifest after shipping; alternatively, decreases may indicate utilization as these enzymes work to neutralize increases in reactive oxygen species.

Influence of selenium and/or magnesium on alleviation alcohol induced oxidative stress in rats, normalization function of liver and changes in serum lipid parameters.

The aim of this study was to evaluate the attenuating effect of given selenium and/or magnesium on ethanol-induced oxidative stress, disturbances of liver function and cholesterol metabolism. Forty male rats were divided into five groups: C - control, Et - intoxicated with alcohol (15% solution in drinking water), Et + Mg, Et + Se, Et + Mg + Se - intoxicated with alcohol and supplemented with selenium (0.4 mg Se/l water), magnesium (100 mg Mg/l water) and combination of Se and Mg, respectively. The experiment was carried out over the 3 months. The results show that the chronic ingestion of alcohol induces lipid peroxidation and histopathological changes in liver. Supplementation with magnesium only partially alleviates oxidative stress and damages in this tissue. The both selenium alone and combination of magnesium and selenium significantly elevated total antioxidant status (TAS) in serum, activity of glutathione peroxidase and ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) in liver and retarded oxidative stress and histopathological changes in this tissue. Chronic administration of ethanol (alone and with magnesium) resulted in significant decrease in the serum total cholesterol and retardation in the body weight gain in comparison with the control group. In the groups supplemented with selenium and selenium and magnesium simultaneously, concentration of total cholesterol in serum and body gains was similar to the control group. Supplementation of Se or selenium and magnesium simultaneously significantly enhances antioxidant defence and is more effective against alcohol-induced oxidative stress, disturbance of liver function and cholesterol metabolism than the separate use of magnesium.

Effects of melatonin on lipid peroxidation and antioxidative enzyme activities in the liver, kidneys and brain of rats administered with benzo(a)pyrene.

Benzo(a)pyrene [B(a)P] is a widespread pollutant with a mutagenic, carcinogenic and strong prooxidative properties. The present study evaluated the melatonin effects on lipid peroxidation products levels and on activity of antioxidative enzymes in the course of B(a)P intoxication. Control rats were treated with 0.9% NaCl; another group was given 10mg melatonin/kg bw; a third group was injected twice a week with B(a)P at the dose of 10mg/kg bw; the fourth group received both B(a)P and melatonin at the dose as mentioned above. The experiment continued for 3 months. In homogenates of brain, liver and kidneys lipid peroxidation was appraised by evaluation of malonyldialdehyde and 4-hydroxyalkenal (MDA+4HDA) levels. Activities of glutathione peroxidase (GPx), superoxide dysmutase (SOD) and catalase (CAT) and concentration of reduced glutathione (GSH) were also estimated. In animals receiving both B(a)P and melatonin, lower levels of MDA+4HDA were observed in all organs as compared to the group treated with B(a)P only. Following administration of B(a)P, GSH level decreased in brain and kidney. Melatonin in combination with B(a)P induced rises in the GSH level in liver and brain, as compared to the receiving B(a)P alone. The activity of SOD increased in the rats treated with melatonin alone but the highest activity was observed in rats treated with B(a)P plus melatonin. CAT activity in the melatonin-treated group increased in brain and liver. Similar to SOD, activity of the enzyme significantly increased in the group treated in combination with B(a)P and melatonin, as compared to the remaining groups in all tested tissues. The results suggest that melatonin protects cells from the damaging action of B(a)P. According to our knowledge, there are no studies describing the effects of melatonin on lipid peroxidation markers and antioxidative enzymes during intoxication of B(a)P in the brain, liver and kidneys. The results of present study give a perspective for further studies of its free radical scavenger properties in prevention of oxidative stress dependent diseases, among others cancers caused by carcinogens such as B(a)P.

Levels of hemoglobin and lipid peroxidation metabolites in blood, catalase activity in erythrocytes and peak expiratory flow rate in subjects with passive exposure to tobacco smoke.

INTRODUCTION: Exposure to tobacco smoke is an extremely important risk factor determining the development of respiratory diseases, cardiovascular diseases and cancer. Passive exposure is common and often not realized by the exposed subjects. Markers of tobacco smoke exposure are nicotine metabolites, i.e. cotinine and trans-3'-hydroxycotinine. OBJECTIVES: The objective of the study was to assess the level of passive exposure to tobacco smoke among students and the exposure impact on the blood hemoglobin level, peak expiratory flow (PEF), lipid peroxidation level and antioxidant enzyme activity. PATIENTS AND METHODS: A total of 104 subjects were enrolled in the study. The subjects were categorized in 3 subgroups depending on nicotine metabolite levels in blood (subgroup I with metabolite level > 100 ng/ml (high exposure); subgroup II with the metabolite level of 10-100 ng/ml; subgroup III with metabolite level <10 ng/ml). The blood hemoglobin level, PEF, levels of lipid peroxidation metabolites--malondialdehyde and 4-hydroxynonenal (MDA + 4-HNE) and catalase (CAT) activity were determined in all the subjects. RESULTS: The study showed statistically significant differences in levels of lipid peroxidation metabolites and CAT activity. Levels of MDA + 4-HNE were higher in subgroup I than in subgroup II or III (I: 3.84 +/- 1.64 mmol/l; II: 2.25 +/- 0.94 mmol/l; III: 1.90 +/- 0.82 mmol/l; pI-II < 0.01; pI-III <0.001). CAT activity was statistically significantly lower in subgroup I than in subgroup III (I: 0.38 +/- 0.01 x 10(6) IU/g hemoglobin [Hb]; II: 0.38 +/- 0.03 x 10(6) IU/g Hb; III: 0.41 +/- 0.04 x 10(6) IU/g Hb; pI-III <0.05). CONCLUSIONS: Passive exposure to tobacco smoke in the study population of students is common. The observed effects of passive exposure to tobacco smoke are similar to those of active smoking. It is postulated to undertake actions aiming at limiting passive exposure to tobacco smoke.

Melatonin stimulates the activity of protective antioxidative enzymes in myocardial cells of rats in the course of doxorubicin intoxication.

The study aimed at determining the effect of melatonin on the activity of protective antioxidative enzymes in the heart and of lipid peroxidation products in the course of intoxication with doxorubicin (DOX). The rats were categorized into four groups, receiving: 0.9% NaCl i.p. (NaCl control); melatonin [20 mg/kg body weight (b.w.)] s.c. (control Mel); DOX (2.5 mg/kg b.w.) i.p.; melatonin plus DOX in doses as above. All the substances were administered once in a week for four consecutive weeks. Homogenates of heart tissue were examined for activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), levels of reduced glutathione (GSH) and of lipid peroxidation indices (MDA + 4-HDA). Administration of melatonin alone did not induce alterations in levels of MDA + 4-HDA, GSH, or in activity of GPx, SOD or CAT, as compared to the group receiving 0.9% NaCl. GSH levels decreased following DOX but remained at normal levels following DOX and melatonin. The level of MDA + 4-HDA increased following DOX, as compared with the control, a change prevented by the combination of DOX + melatonin. Activities of GPx, SOD and CAT were higher in groups receiving DOX and/or DOX plus melatonin than in control groups. Activity of CAT and the level of GSH in the group receiving DOX plus melatonin were significantly higher than in the group intoxicated with DOX alone. The obtained results demonstrate that, when given in parallel with DOX, melatonin protects cardiomyocytes from damaging effects of the cytostatic drug (reflected by the levels of MDA + 4-HDA). The protective effect resulted, in part from the augmented levels of GSH and from stimulation of CAT activity by melatonin in cardiomyocytes subjected to the action of DOX.

Role of exogenous melatonin in reducing the nephrotoxic effect of daunorubicin and doxorubicin in the rat.

The aim of these studies was to examine the nephroprotective effect of melatonin following the anthracycline administration [daunorubicin (DNR); doxorubicin (DOX)] in rats. Application of these drugs in chemotherapy is limited because of their cardiotoxicity and nephrotoxicity. Rats of the Buffalo strain were divided into groups according to the cytostatic drug used, its dose and sequence of administration [DNR or DOX single (i.v.) dose of 10 mg/kg b.w., i.e. acute intoxication and 3 mg/kg b.w. (i.v.) weekly for 3 wk, subchronic intoxication]. Melatonin was administered subcutaneously before and after every injection of a cytostatic drug at a dose of 10 mg/kg b.w. The severity of renal alterations was examined both biochemically [levels of lipid peroxidation markers, malonyldialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)], or histologically. A statistically significant decrease in renal damage was noted after melatonin administration to acutely or subchronically intoxicated DNR-treated and DOX-treated rats. Biochemical assays revealed significant decreases in MDA and 4-HDA levels following application of melatonin during subchronic DNR or DOX intoxication. In summary, melatonin was found to exert a protective effect on the kidney, which was particularly evident after subchronic DOX and DNR intoxication, using both histological or biochemical methods.