VIP/PACAP signaling as an alternative target during hyperoxic exposure in preterm newborns.

The use of oxygen therapy (high doses of oxygen - hyperoxia) in the treatment of premature infants results in their survival. However, it also results in a high incidence of chronic lung disease known as bronchopulmonary dysplasia, a disease in which airway hyper-responsiveness and pulmonary hypertension are well known as consequences. In our previous studies, we have shown that hyperoxia causes airway hyper-reactivity, characterized by an increased constrictive and impaired airway smooth muscle relaxation due to a reduced release of relaxant molecules such as nitric oxide, measured under in vivo and in vitro conditions (extra- and intrapulmonary) airways. In addition, the relaxation pathway of the vasoactive intestinal peptide (VIP) and/or pituitary adenylate cyclase activating peptide (PACAP) is another part of this system that plays an important role in the airway caliber. Peptide, which activates VIP cyclase and pituitary adenylate cyclase, has prolonged airway smooth muscle activity. It has long been known that VIP inhibits airway smooth muscle cell proliferation in a mouse model of asthma, but there is no data about its role in the regulation of airway and tracheal smooth muscle contractility during hyperoxic exposure of preterm newborns.

Diabetes converts arterial regulation by perivascular adipose tissue from relaxation into H(2)O(2)-mediated contraction.

This study aims to reveal the reason for the increased force of 5-hydroxytryptamine-induced contraction of endothelium-denuded skeletal muscle arteries of diabetic rats in the presence of perivascular adipose tissue (PVAT). Our data on rat gracilis arteries show that i) PVAT of skeletal muscle arteries of healthy and diabetic rats releases hydrogen peroxide (H(2)O(2)), ii) higher concentrations of 5-hydroxytryptamine increase the production of H(2)O(2) in PVAT; iii) an enhanced PVAT production of H(2)O(2) is the main, if not the only, reason for the sensitization of arterial contraction to 5-hydroxytriptamine-induced contraction in diabetes and iv) endothelium antagonizes the effect of PVAT-derived H(2)O(2).

The relationship between antioxidant enzymes and lipid peroxidation in senescent rat erythrocytes.

The aim of this study was to gain more complete information about the relationships between some endogenous antioxidants and the malondialdehyde (MDA) as a marker of lipid peroxidation, during D-galactose induced senescence. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and the concentrations of uric acid (UA) in plasma and MDA in erythrocyte's hemolysate, were determined in 15 D-galactose (D-gal), treated rats and compared with 15 placebo. The activity of the erythrocyte's CAT was found significantly increased due to the senescence. The ratio of the activities of antioxidant enzymes R=SOD/(GPx+CAT) was significantly decreased due to the senescence and negatively correlated with the MDA (rho=-0.524, p=0.045). The antioxidant enzymes SOD and GPx negatively correlated with the MDA, while CAT displayed no correlation. Further, the UA positively correlated with the ratio of activities of the antioxidant enzymes R=SOD/(GPx+CAT), (rho=0.564, p=0.029 for senescent rats). Obtained results may contribute to better understanding of the process of D-gal induced senescence in the erythrocytes.

D-galactose induced changes in enzymatic antioxidant status in rats of different ages.

Considering the preexisting influence of the process of natural aging on antioxidant enzymes activity and the level of lipid peroxidation, the age of the rats at which D-galactose (D-gal) treatment is started could strongly impact the development of D-gal induced senescence. To evaluate this, we subjected 1, 3 and 15 months old rats to D-gal treatment in parallel with having appropriate placebos (0.9 % saline). Our results showed elevated glutathione peroxidase (GPx) activity and no significant changes in superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) activity or malondialdehyde (MDA) levels in relation to natural aging. In mature and aged senescent livers we observed positive correlation between increased ratio R=SOD/(GPx+CAT) and increased MDA concentration. MDA levels seemed to correlate positively with the age of the animals at which D-gal treatment had started. In the case of 3 and 15 months old rats there was D-gal induced decrease in SOD and GR activity, but this effect of the treatment was not observed in 1 month old rats. Our results imply that the changes in the antioxidant enzyme activities are not only under the influence of the D-gal overload, but also depend on the developmental stage of the rats. According to our results, with regard to enzymatic antioxidant capacity and the level of lipid peroxidation, the best age for induction of senescence is somewhere after the third month.

Influence of chronic chromium exposition on the processes of lipid peroxidation inflammation and platelet activation in rats.

The aim of this study was to investigate the effect of chronic treatment with chromium hexavalent (Cr VI) on the platelet activation, inflammation and lipid peroxidation in rats. Thirty male Wistar rats weighing 251 ± 18 g were randomly assigned to one control and one Cr-exposed group. 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), interleukin 1ß (IL-1ß), tumor necrosis factor alpha (TNF-alpha) and creatinine (Crt), were measured in plasma, while 11-dehydro thromboxane B2 (11-dehydro-TXB2) in plasma andurine. Plasma levels of IL-1ß, TNF-alpha, 8-iso-PGF(2α) and Crt were significantly increased in the Cr (VI)-treated in comparison to the control group. Also, in the urine of Cr (VI)-treated rats, 11-dehydro-TXB2 was significantly increased in comparison to control rats. From the obtained data it is evident that chronic treatment with Cr (VI), accelerates arachidonic acid peroxidation in rats, which peroxidation further probably induces enhanced 11-dehydro-TXB2 excretion rate.

Age and heat exposure-dependent changes in antioxidant enzymes activities in rat's liver and brain mitochondria: role of alpha-tocopherol.

To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.