Lidia Januszewska

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

Abstract: 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 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).

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

Abstract:  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.

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.

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

Abstract 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. Cilj je ovog istraživanja bio ocijeniti učinke kronične izloženosti kombinaciji Cd, Pb i Mn u niskim dozama kakve su u okolišu na oksidativni stres u jetrima i srcu štakora te na pokazatelje jetrene funkcije. U tu smo svrhu mužjake Wistar štakora nasumce podijelili u osam skupina, od kojih je kontrolna pila čistu vodu, a izložene skupine vodu pomiješanu s olovom (0,2 mg L-1), kadmijem (1 mg L-1) i manganom (2 mg L-1), zasebno ili u kombinacijama. Koncentracija malondialdehida (MDA) značajno se povećala u oba organa životinja izloženih kombinacijama metala. Srčani MDA korelirao je s razinama kadmija, olova i mangana u krvi, a jetreni MDA s razinom kadmija u krvi. Aktivnost aspartat aminotransferaza (AST) i koncentracije bilirubina također su bile značajno povišene u skupini izloženoj svim trima metalima te su korelirale s razinama kadmija, olova i mangana u krvi. Rezultati istraživanja potvrdili su da zajedno ova tri metala djeluju na povećanje MDA u srcu. Slična je sinergija zamijećena i između olova i mangana s obzirom na povećanje razine alanin aminotransferaze (ALT) u serumu, koji je pokazatelj jetrene funkcije.

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.

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.

Effects of chronic exposure to lead, cadmium, and manganese mixtures on oxidative stress in rat liver and heart / Utjecaj kronične istodobne izloženosti olovu, kadmiju i manganu na oksidativni stres u jetri i srcu štakora

Abstract 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. Cilj je ovog istraživanja bio ocijeniti učinke kronične izloženosti kombinaciji Cd, Pb i Mn u niskim dozama kakve su u okolišu na oksidativni stres u jetrima i srcu štakora te na pokazatelje jetrene funkcije. U tu smo svrhu mužjake Wistar štakora nasumce podijelili u osam skupina, od kojih je kontrolna pila čistu vodu, a izložene skupine vodu pomiješanu s olovom (0,2 mg L-1), kadmijem (1 mg L-1) i manganom (2 mg L-1), zasebno ili u kombinacijama. Koncentracija malondialdehida (MDA) značajno se povećala u oba organa životinja izloženih kombinacijama metala. Srčani MDA korelirao je s razinama kadmija, olova i mangana u krvi, a jetreni MDA s razinom kadmija u krvi. Aktivnost aspartat aminotransferaza (AST) i koncentracije bilirubina također su bile značajno povišene u skupini izloženoj svim trima metalima te su korelirale s razinama kadmija, olova i mangana u krvi. Rezultati istraživanja potvrdili su da zajedno ova tri metala djeluju na povećanje MDA u srcu. Slična je sinergija zamijećena i između olova i mangana s obzirom na povećanje razine alanin aminotransferaze (ALT) u serumu, koji je pokazatelj jetrene funkcije.

Utjecaj kronične istodobne izloženosti olovu, kadmiju i manganu na oksidativni stres u jetri i srcu štakora

Abstract 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. Cilj je ovog istraživanja bio ocijeniti učinke kronične izloženosti kombinaciji Cd, Pb i Mn u niskim dozama kakve su u okolišu na oksidativni stres u jetrima i srcu štakora te na pokazatelje jetrene funkcije. U tu smo svrhu mužjake Wistar štakora nasumce podijelili u osam skupina, od kojih je kontrolna pila čistu vodu, a izložene skupine vodu pomiješanu s olovom (0,2 mg L-1), kadmijem (1 mg L-1) i manganom (2 mg L-1), zasebno ili u kombinacijama. Koncentracija malondialdehida (MDA) značajno se povećala u oba organa životinja izloženih kombinacijama metala. Srčani MDA korelirao je s razinama kadmija, olova i mangana u krvi, a jetreni MDA s razinom kadmija u krvi. Aktivnost aspartat aminotransferaza (AST) i koncentracije bilirubina također su bile značajno povišene u skupini izloženoj svim trima metalima te su korelirale s razinama kadmija, olova i mangana u krvi. Rezultati istraživanja potvrdili su da zajedno ova tri metala djeluju na povećanje MDA u srcu. Slična je sinergija zamijećena i između olova i mangana s obzirom na povećanje razine alanin aminotransferaze (ALT) u serumu, koji je pokazatelj jetrene funkcije.