Chronic effects of platinum(IV) complex and its diamine ligand on rat heart function: comparison with cisplatin

Mitochondrial dysfunction plays crucial role in the pathologenesis of myocardial infarction (MI). The present study evaluated the protective effect of α-bisabolol against isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. Male albino Wistar rats were pre- and co-treated with intraperitoneal injection of α-bisabolol (25 mg/kg body weight) daily for 10 days. To induce experimental MI, ISO (85 mg/kg body weight) was injected subcutaneously to the rats at an interval of 24 h for 2 days (9th and 10th day). ISO-induced MI was indicated by the decreased activities of heart creatine kinase and lactate dehydrogenase in rats. ISO administration also enhanced the concentrations of heart mitochondrial lipid peroxidation products and decreased the activities/concentrations of mitochondrial antioxidants, Kreb’s cycle dehydrogenases and mitochondrial electron transport chain complexes I, II?+?III and IV in rats. Furthermore, ISO triggers calcium overload and ATP depletion in the rat’s heart mitochondria followed by the mitochondrial cytochrome-C release and the activation of intrinsic pathway of apoptosis by upregulating the myocardial pro-apoptotic Bax, P⁵³, APAF-1, active caspase-3, active caspase-9 and down regulating the expressions of anti-apoptotic Bcl-2. α-Bisabolol pre and co-treatment showed considerable protective effects on all the biochemical and molecular parameters studied. Transmission electron microscopic study and mitochondrial swelling assay confirmed our biochemical and molecular findings. The in vitro study on hydroxyl radical also revealed the potent free radical scavenging activity of α-bisabolol. Thus, α-bisabolol attenuates mitochondrial dysfunction and intrinsic pathway of apoptosis in ISO-induced myocardial infarcted rats.

     

Long-term impact of war on healthcare costs: an eight-country study

Objective

Exposure to war can negatively affect health and may impact on healthcare costs. Estimating these costs and identifying their predictors is important for appropriate service planning. We aimed to measure use of health services in an adult population who had experienced war in the former-Yugoslavia on average 8 years previously, and to identify characteristics associated with the use and costs of healthcare.

Method

War-affected community samples in Bosnia-Herzegovina, Croatia, Kosovo, FYR Macedonia, and Serbia were recruited through a random walk technique. Refugees in Germany, Italy and the UK were contacted through registers, organisations and networking. Current service use was measured for the previous three months and combined with unit costs for each country for the year 2006/7. A two-part approach was used, to identify predictors of service use with a multiple logistic regression model and predictors of cost with a generalised linear regression model.

Results

3,313 participants were interviewed in Balkan countries and 854 refugees in Western European countries. In the Balkan countries, traumatic events and mental health status were related to greater service use while in Western countries these associations were not found. Participants in Balkan countries with post traumatic stress disorder (PTSD) had costs that were 63% higher (p = 0.005) than those without PTSD. Distress experienced during the most traumatic war event was associated with higher costs (p = 0.013). In Western European countries costs were 76% higher if non-PTSD anxiety disorders were present (0.027) and 63% higher for mood disorders (p = 0.006).

Conclusions

War experiences and their effects on mental health are associated with increased health care costs even many years later, especially for those who stayed in the area of conflict. Focussing on the mental health impact of war is important for many reasons including those of an economic nature.     

Protective role of fructose in the metabolism of astroglial C6 cells exposed to hydrogen peroxide

Astroglial cells represent the main line of defence against oxidative damage related to neurodegeneration. Therefore, protection of astroglia from an excess of reactive oxygen species could represent an important target of the treatment of such conditions. The aim of our study was to compare the abilities of glucose and fructose, the two monosaccharides used in diet and infusion, to protect C6 cells from hydrogen peroxide (H₂O₂)-mediated oxidative stress. It was observed using confocal microscopy with fluorescent labels and the MTT test that fructose prevents changes of oxidative status of the cells exposed to H₂O₂ and preserves their viability. Even more pronounced protective effects were observed for fructose 1,6-bis(phosphate). We propose that fructose and its intracellular forms prevent H₂O₂ from participating in the Fenton reaction via iron sequestration. As fructose and fructose 1,6-bis(phosphate) are able to pass the blood–brain barrier, they could provide antioxidative protection of nervous tissue in vivo. So, in contrast to the well-known negative effects of frequent consumption of fructose under physiological conditions, acute infusion or ingestion of fructose or fructose 1,6-bis(phosphate) could be of benefit in the cytoprotective therapy of neurodegenerative disorders related to oxidative stress.     

Comparative study of 137Cs distribution in broilers and pheasants and possibilities for protection

The aim of the present study was to investigate distribution of (137)Cs in leg and breast meat of broilers and pheasants following single alimentary contamination and administration of two protectors (AFCF and clinoptilolite). The birds were administered a single dose of (137)CsCl, with an activity of 750?Bq. Protectors were given via gastric tube or mixed in the forage pellets. AFCF given via gastric tube decreased the (137)Cs concentration by a factor of 7.8 in broilers leg meat and 7.4 in broilers breast meat. When AFCF was mixed in pellets, the (137)Cs concentration was 19.5 times lower in broilers leg meat and 22.1 times lower in broilers breast meat, than in the control group. In pheasants, AFCF administered via gastric tube decreased the (137)Cs concentration by a factor of 12.4 in leg meat and by a factor of 13.7 in breast meat, respectively. In group 4, where pheasants were administered AFCF mixed in pellets, the (137)Cs concentration was 3.7 times lower in leg and breast meat, than in the control group. For comparison, clinoptilolite administered via gastric tube decreased the (137)Cs concentration 1.8 times in broilers leg meat and 2.0 times in breast meat, compared to the control group. In pheasants, (137)Cs concentration was 2.9 times lower in leg meat and 2.6 times lower in breast meat. Clinoptilolite mixed in the feed had relatively low efficiency of protection in broilers ((137)Cs concentration was 1.4 times lower in leg meat and 1.6 lower in breast meat). A similar trend was observed in pheasants ((137)Cs concentration was 1.6 lower in leg and breast meat).     

Consequences of MnSOD interactions with nitric oxide: nitric oxide dismutation and the generation of peroxynitrite and hydrogen peroxide

The present study demonstrates that manganese superoxide dismutase (MnSOD) (Escherichia coli), binds nitric oxide (^√NO) and stimulates its decay under both anaerobic and aerobic conditions. The results indicate that previously observed MnSOD-catalyzed ^√NO disproportionation (dismutation) into nitrosonium (NO⁺) and nitroxyl (NO^- ) species under anaerobic conditions is also operative in the presence of molecular oxygen. Upon sustained aerobic exposure to ^√NO, MnSOD-derived NO^-  species initiate the formation of peroxynitrite (ONOO^- ) leading to enzyme tyrosine nitration, oxidation and (partial) inactivation. The results suggest that both ONOO^-  decomposition and ONOO^- -dependent tyrosine residue nitration and oxidation are enhanced by metal centre-mediated catalysis. We show that the generation of ONOO^-  is accompanied by the formation of substantial amounts of H₂O₂. MnSOD is a critical mitochondrial antioxidant enzyme, which has been found to undergo tyrosine nitration and inactivation in various pathologies associated with the overproduction of ^√NO. The results of the present study can account for the molecular specificity of MnSOD nitration in vivo. The interaction of ^√NO with MnSOD may represent a novel mechanism by which MnSOD protects the cell from deleterious effects associated with overproduction of ^√NO.     

Oxidative stress and nitrite dynamics under maximal load in elite athletes: relation to sport type

Maximal workload in elite athletes induces increased generation of reactive oxygen/nitrogen species (RONS) and oxidative stress, but the dynamics of RONS production are not fully explored. The aim of our study was to examine the effects of long-term engagement in sports with different energy requirements (aerobic, anaerobic, and aerobic/anaerobic) on oxidative stress parameters during progressive exercise test. Concentrations of lactates, nitric oxide (NO) measured through stabile end product-nitrites (NO₂ ^?), superoxide anion radical (O₂ ^??), and thiobarbituric reactive substances (TBARS) as index of lipid peroxidation were determined in rest, after maximal workload, and at 4 and 10th min of recovery in blood plasma of top level competitors in rowing, cycling, and taekwondo. Results showed that sportmen had similar concentrations of lactates and O₂ ^?? in rest. Nitrite concentrations in rest were the lowest in taekwondo fighters, while rowers had the highest levels among examined groups. The order of magnitude for TBARS level in the rest was bicycling > taekwondo > rowing. During exercise at maximal intensity, the concentration of lactate significantly elevated to similar levels in all tested sportsmen and they were persistently elevated during recovery period of 4 and 10 min. There were no significant changes in O₂ ^??, nitrite, and TBARS levels neither at the maximum intensity of exercise nor during the recovery period comparing to the rest period in examined individuals. Our results showed that long term different training strategies establish different basal nitrites and lipid peroxidation levels in sportmen. However, progressive exercise does not influence basal nitrite and oxidative stress parameters level neither at maximal load nor during the first 10 min of recovery in sportmen studied.     

Spleen and cardiovascular function during short apneas in divers.

We investigated the spleen volume changes as related to the cardiovascular responses during short-duration apneas at rest. We used dynamic ultrasound splenic imaging and noninvasive photoplethysmographic cardiovascular measurements before, during, and after 15-20 s apneas in seven trained divers. The role of baroreflex was studied by intravenous bolus of vasodilating drug trinitrosan during tidal breathing. The role of lung volume was studied by comparing the apneas at near-maximal lung volume with apneas after inhaling tidal volume, with and without cold forehead stimulation. In apneas at near maximal lung volume, a 20% reduction in splenic volume (P = 0.03) was observed as early as 3 s after the onset of breath holding. Around that time the heart rate increased, the mean arterial pressure abruptly decreased from 89.6 to 66.7 mmHg (P = 0.02), and cardiac output decreased, on account of reduction in stroke volume. Intravenous application of trinitrosan resulted in approximately 6-mmHg decrement in mean arterial pressure, while the splenic volume decreased for approximately 13%. In apneas at low lung volume, the early splenic contraction was also observed, 10% without and 12% with cold forehead stimulation, although the mean arterial pressure did not change or even increased, respectively. In conclusion, the spleen contraction is present at the beginning of apnea, accentuated by cold forehead stimulation. At large, but not small, lung volume, this initial contraction is probably facilitated by downloaded baroreflex in conditions of decreased blood pressure and cardiac output.     

Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities?

The concept of an anti-oxidant defence system as a means to prevent oxidative cell damage implies balanced activities of anti-oxidant defence enzymes. As well as positive correlations between anti-oxidant enzyme activities in human erythrocytes, it has been observed that sometimes when glutathione peroxidase activity is increased, CuZn-superoxide dismutase activity is decreased. In our current study we have examined the plasma lipid profile and the anti-oxidant defence enzymes in erythrocytes from humans, pigs, and bulls. We found that a negative correlation existed between CuZn-superoxide dismutase and glutathione peroxidase activities in human erythrocytes when the concentrations of both plasma triglycerides and total cholesterol were high. This correlation was also found in pig erythrocytes, but not in bull erythrocytes. We propose that cholesterol could affect membrane lipid peroxidation and superoxide generation in erythrocytes via the recently found fraction of cholesterol bound to haemoglobin, termed haemoglobin-cholesterol.