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.

Effects of adaptive exercise on apoptosis in cells of rat renal tubuli.

Regular exercise is known to improve physiological and functional capacity of many organs due to adaptive processes. We have previously shown that acute exercise in untrained rats results in apoptosis of renal tubular cells and that the apoptotic process seems to be associated with stimulation of angiotensin II, AT1 and AT2 receptors. In this study, we examined the influence of regular training on apoptosis and the role of angiotensin II receptors and antioxidant enzymes in mediating the adaptive response in renal tubular cells. We measured apoptosis, expression of AT1 and AT2 receptors, level of lipid peroxidation (TBARS) and activities of antioxidant enzymes, SOD, GPx and CAT in kidneys of sedentary rats that were exposed to acute exercise and rats that were trained for 8 weeks. In untrained animals, the acute exercise resulted in increased apoptosis and increased expression of AT1 and AT2 receptors in renal tubular cells, while in the rats exposed to the 8-week regular training, there were no changes in apoptosis nor AT1 and AT2 receptor expression as compared to the sedentary animals. The TBARS levels were significantly increased in acutely exercised rats, while in rats pre-exposed to the training they remained unchanged. The acute exercise, as well as regular training, did not change SOD, CAT or GPx activities. These findings suggested that the acute exercise-induced apoptosis in renal tubules could involve action of AT1 and AT2 receptors as well as oxidative stress, while the regular training was shown to prevent apoptosis in renal tubular cells via modulated expression of AT1 and AT2 receptors.

Expression of metallothionein in renal tubules of rats exposed to acute and endurance exercise.

The induction of exercise-induced apoptosis in not actively involved in exercise organs, such as kidney could be a result of oxidative stress. Metallothionein (MT) exerts a protective effect in the cell against oxidative stress and apoptosis. We have previously demonstrated an increased incidence of apoptosis in distal tubular cells and collecting ducts in rat kidney after acute exercise. The present study was designed to test the hypothesis that MT may play a protective role in rat renal tubules against exercise-induced apoptosis after the acute exercise and regular training. Male Wistar rats were divided into control, acute exercised and 8-wk regularly trained groups. The kidneys were removed after a rest period of 6 h and 96 h. The ultrastructure of renal tubular cells was examined by electron microscopy. Apoptosis was detected in paraffin sections by the TUNEL technique. Expression of MT was examined by immunohistochemistry. The level of lipid peroxidation (thiobarbituric acid reactive substances - TBARS) was assayed in renal tissue homogenates. After acute exercise, the occurrence of apoptosis was restricted to distal tubules and collecting ducts of rat kidney, whereas the proximal tubules remained unaffected. The 8-wk training did not result in increased apoptosis in tubular cell. MT expression was confined exclusively to proximal tubules in all groups. However, it was significantly increased in acutely exercised animals, as compared to control and trained rats. After the 8-wk training, MT expression remained unaltered as compared to the control group. TBARS levels were significantly increased after acute exercise, while after regular training they remained unchanged. A significant correlation between TBARS level and MT expression was demonstrated. The findings could suggest a protective role of MT against oxidative stress and apoptosis in proximal tubular cells.

Exercise-induced apoptosis in renal tubular cells of the rat.

A number of studies have shown that acute physical exercise is associated with the induction of apoptosis not only in skeletal muscle but also in many distant organs. One of the pathogenic agents responsible for exercise-induced damage in many tissues is the generation of oxygen free radicals. The aim of the present study was to examine the influence of exercise-induced oxidative stress on the rat kidney. The analysis was performed on the kidneys of rats subjected to treadmill running until exhaustion. Our results demonstrated that acute exercise led to apoptotic damage of the renal distal tubular cells, although this was not a result of oxidative stress.

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.

[Effect of endurance exercise on blood levels of leptin in women and men]. / Wplyw wysilku wytrzymalosciowego na stezenie leptyny we krwi kobiet i mezczyzn.

Leptin is a peptide hormone secreted by adipose tissue which takes part in regulation of food intake and energy expenditure. The aim of the study was to evaluate an endurance exercise influence on leptin levels and its relation with lipids parameters and energy expenditure during an effort. Forty two cyclists (16 women and 26 men) have performed a progressive test. Before and after an effort the blood was taken to evaluation of leptin level and lipid profile. During the test and the recovery ventilation, maximal oxygen uptake, heart rate and energy utilization were analyzed. All parameters were analyzed in whole cyclists' group and in women and men groups separately. We have observed that in women the leptin concentration in serum were significantly higher than in men before exercise as well as after an effort. Moreover female cyclists showed a reduction in leptin levels after progressive test compared with any changes in men cyclists. In the whole group, after an effort, we observed a positive correlation between leptin levels and BMI and apoB, but a negative correlation with energy expenditure and VO2max. We have also noted a positive correlation between energy expenditure and VO2max. In conclusion we can say that the negative correlation between leptin and energy expenditure, ventilation and maximal oxygen uptake is related to physical performance. The decrease of serum leptin in women without any changes in men could have been mediated by gender differences in body fat tissue as well as hormonal (influence of catecholamins, cortisol, thyroid hormones and growth hormone on adipose tissue, augmentation of testosterone in men) and peripheral mechanisms (decrease of glucose or insulin and increase of fatty acids).

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.

Effect of smoking and alcohol consumption on the serum selenium level of Lower Silesian population.

Serum selenium (Se) levels and glutathione peroxidase (GSH-Px) activity in erythrocytes have been determined for a healthy Lower Silesian population. The results have been analysed in relation to smoking and alcohol consumption habits. The mean concentration of serum Se for the group is within the lower range and appears to be significantly lower in the group of smokers that was studied (smoking over 20 cigarettes/day, mean concentration value = 50.8 microg/l), compared to non-smokers (mean value = 78.8 microg/l). For men that smoke, the concentration is lower than that found for smoking women, however, the difference is without statistical significance. Regarding GSH-Px activity, no difference between the smoking and non-smoking groups has been found (mean values = 19.84 and 20.92 U/gHb, respectively). From the group of people examined, we have selected those who drink an equivalent of 50 g or more of pure ethanol per week. For this group the serum Se level has been found to be lower compared to the group that does not consume that much alcohol. However, the difference is without statistical significance. We have found no correlation between age and the parameters studied (serum Se concentration and GSH-Px activity).

[Physiological mechanisms of physical activity affecting health]. / Fizjologiczne mechanizmy aktywnosci fizycznej w dzialaniu na zdrowie.

Movement is a genetically determined functional feature of the human organism that can be modified by environmental factors and by behavioral influences. Caused by physical activity homeostatic changes have many aspects of stress reaction giving positive and/or negative health effects. In the paper there are presented main aspects of these effects with a special reference to the mechanisms of their appearance.