This study was designed to determine the gastroprotective properties of quercetin in ischemia/reperfusion-induced gastric mucosal injury and the involvement of endogenous prostaglandins in this process. Oral pretreatment of rats with quercetin (100 mg.kg-1) 30 min before surgery significantly decreased the length of gastric mucosal lesions. However, lower doses of quercetin (25 and 50 mg.kg-1) only slightly decreased the gastric mucosal injury. Intraperitoneal application of indomethacin (5 mg.kg-1) had no effect in control (sham-operated) animals, but significantly worsened gastric injury in non-treated animals after ischemia/reperfusion. Furthermore, indomethacin only slightly reversed protective effect of quercetin. Non-treated animals showed a marked decrease in adherent mucus after ischemia/reperfusion. On the other hand, application of quercetin prevented this significant decrease even in animals pretreated with indomethacin. It can be concluded that antioxidant properties of quercetin and its mucus protective effect might be the main factors responsible for its protective effect against ischemia/reperfusion-induced gastric mucosal injury., J. Mojžiš, K. Hviščová, D. Germanová, D. Bukovičová, L. Mirossay., and Obsahuje bibliografii
An attempt was made to determine the relationship between the characteristics of electrical activity of the hypertrophied myocardium of rats at the cellular level and at the level of the whole heart after a one-month left ventricular pressure overload. Such an animal model has already been demonstrated to be highly resistant to epinephrine-induced arrhythmias. Since severe ventricular arrhythmias often occur in patients with cardiac hypertrophy, ventricular vulnerability might depend on some electrophysiological characteristics of the heart related to the stage of hypertrophy. Using the "floating" microelectrode technique, the computed characteristics of cardiac transmembrane action potentials (AP) of the left and right epicardium cells were compared in situ to computed characteristics of the electrocardiograms in anaesthetized control rats (group C) and in rats with left ventricular hypertrophy (group H) induced by a one-month suprarenal constriction of the abdominal aorta. The aortic pressure overload caused a significant (p< 0.001) and marked increase in AP duration of left ventricular cells: APD 30 and APD 80 were 29 ±3 ms and 89 ±6 ms, respectively, in group H and 14 ±1 ms and 53 ±2 ms in group C. The same modifications were observed in right ventricular cells when right hypertrophy was present. Simultaneous electrocardiograms exhibited a significant (p<0.01) prolongation of P-R, Q-S and T duration and T wave flattening in group H (63 ±2 ms, 32 ±3 ms, 109 ±5 ms and 0.25 ±0.03 mV as compared with 53 ±1 ms, 20 ±1 ms, 88 ±2 ms and 0.40 ±0.04 mV in group C). After a one-month aortic overload in rats, both left and right ventricles are hypertrophied and have the same electrophysiological characteristics: in this model, at this stage of hypertrophy, some factors favouring ventricular arrhythmias are missing. The corresponding flattening of the T wave in the ECG might be of clinical relevance.
Resveratrol is a polyphenol found in different plant species and having numerous health-promoting properties in animals and humans. However, its protective action against deleterious effects of ethanol is poo rly elucidated. In the present study, the influence of resveratrol (10 mg/kg/day) on some hormones and metabolic parameters was determined in rats ingesting 10 % ethanol solution for two weeks. Blood levels of insulin, glucagon and adiponectin were affecte d by ethanol, however, resveratrol partially ameliorated these changes. Moreover, in ethanol drinking rats, liver lipid accumulation was increased, whereas resveratrol was capable of reducing liver lipid content, probably due to decrease in fatty acid synt hesis. Resveratrol decreased also blood levels of triglycerides and free fatty acids and reduced γ-glutamyl transferase activity in animals ingesting ethanol. These results show that resveratrol, already at low dose, alleviates hormonal and metabolic changes induced by ethanol in the rat and may be useful in preventing and treating some consequences o f alcohol consumption., K. Szkudelska, M. Deniziak, P. Roś, K. Gwóźdź, T. Szkudelski., and Obsahuje bibliografii
We studied the response of several parameters related to oxidative stress in the liver of aging rats. Male Wistar rats aged 1.5, 3, 18 and 24 months were used. Livers showed an increase in superoxide anion (O2-) concentration at 1.5 and 18 months of age compared to the 3-month-old group; a decrease in superoxide dismutase (SOD) was seen at 1.5 months and catalase concentrations remained unaltered throughout the aging process. Nitric oxide (NO) progressively declined with age; a significant decrease was particularly apparent at 18 and 24 months of age. Thiobarbituric acid reactive substances (TBARS) decreased significantly at 1.5 months, whereas it increased at 18 and 24 months of age. Concentrations of prostaglandin E2 (PGE2), and adenine nucleotides, and their metabolites, remained unchanged throughout the aging process. Although the mitochondrial damage caused by oxidative stress can result in reduced ATP production and compromised cell function, our results on adenosine nucleotides and their metabolites support the notion that the integrity of mitochondria and enzymatic activity remain mostly unchanged with aging. In conclusion, we observed a significant decrease in the levels of NO in the older groups of rats and hence in its antioxidant activity. This could explain the observed increase in lipid peroxides which suggests an important role for NO in oxidative stress in the liver of older rats., F. Mármol ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Pulmonary hypertension is a group of disorders characterized by elevated mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance. To test our hypothesis that combining two drugs useful in experimental pulmonary hypertension, statins and dehydroepiandrosterone sulfate (DHEA-S), is more effective than either agent alone, we induced pulmonary hypertension in adult male rats by exposing them to hypoxia (10 %O2) for 3 weeks. We treated them with simvastatin (60 mg/l) and DHEA-S (100 mg/l) in drinking water, either alone or in combination. Both simvastatin and DHEA-S reduced mPAP (froma mean±s.d. of 34.4±4.4 to 27.6±5.9 and 26.7±4.8 mmHg, respectively), yet their combination was not more effective (26.7±7.9 mmHg). Differences in the degree of oxidative stress (indicated by malondialdehydeplasma concentration), the rate of superoxide production (electron paramagnetic resonance), or blood nitric oxide levels (chemiluminescence) did not explain the lack of additivity of the effect of DHEA-S and simvastatin on pulmonary hypertension. We propose that the main mechanism of both drugs on pulmonary hypertension could be their inhibitory effect on 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, which could explain their lack of additivity.
Spatial navigation and memory is considered to be a part of the declarative memory system and it is widely used as an animal model of human declarative me mory. However, spatial tests typically involve only static settings, despite the dynamic nature of the real world. Animals, as well as people constantly need to interact with moving objects, other subjects or even with entire moving environments (flowing water, running stairway). Therefore, we design novel spatial tests in dynamic environments to study brain mechanisms of spatial processing in more natural settings with an interdisciplinary approach including neuropharmacology. We also translate data from neuropharmacological studies and animal models into development of novel therapeutic approaches to neuropsychiatric disorders and more sensitive screening tests for impairments of memory, thought, and behavior., A. Stuchlik ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Plasma endothelin-1 (ET-1) levels are elevated in spinal cord injury (SCI), and ET-1 may be involved in the pathophysiology of this condition. However, its effects on contractile function of the heart of SCI rats are still unknown. To define more clearly the possiblel role of ET-1 following SCI, we investigated the effect of ET-1 on the contraction, calcium transients and L-type calcium current (ICa,L) in the cardiomyocytes of control and SCI rats. Sixteen Sprague-Dawley male rats aged 80-100 days and weighing 250-350 g were randomized into control and SCI groups. Fourteen days following compression injury to the spinal cord, effects of ET-1 on the contraction, calcium transients and ICa,L were studied in the cardiomyocytes of control and SCI rats by the technique of simultaneous measurement of intracellular Ca2+ and contraction and by whole-cell configuration of the patch-clamp technique. In myocytes from control rats, ET-1 significantly increased contraction, the magnitude of Ca2+ transients and the peak amplitude of ICa,L. However, ET-1 had little effect on the amplitude of contraction, calcium transients and ICa,L in myocytes from SCI rats. These results suggest that the positive inotropic effects of ET-1 on control myocardial contraction may be altered in pathological states such as SCI., Y.-F. Guo ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Suspension hypokinesia is a new model which can simulate some effects of microgravity on the organism of laboratory animals. Two groups of male SPF-bred Wistar rats were suspended for 24 h. In the first group hypokinesia began in the morning (M) (1 h after light onset, 0800 h), whereas the other group was subjected to this treatment from the evening (E) (1 h after dark onset, 2000 h). In the serum, there was a statistically significant increase in non-esterified fatty acids, triacylglycerols (TG) and glucose and a decrease in triiodothyronine concentration in the M group, while only a significant increase in phospholipids (PL) was found in the E group. The serum corticosterone level was increased in both groups, more markedly in the M group. There was an increase in TG and PL in the liver in M rats. In the bone marrow (femur), an increase of triglycerols in E rats and an increase of phospholipids in M rats were found. The concentration of glycogen in the heart muscle, m. quadriceps femoris and m. soleus rose in the M group only. The changes in the analyzed parameters predominate in the rats subjected to hypokinesia in the morning period. This fact confirmed the hypothesis about a higher sensitivity of rats to the stressor acting in the period of inactivity.
Male Wistar rats adapted to a light/dark cycle (LD) 12:12 h were exposed in the darkness to a single dose of 14.35 Gy gamma rays on the head with the body shielded. Irradiated and sham-irradiated rats were kept again in the 12 h LD cycle with a free access to food and water till the analysis performed in the darkness. Pineal N-acetyltransferase activity and melatonin content, the serum concentration of the melatonin, corticosterone, thyrotropin and thyroid hormones were determined. N-acetyltransferase activity was lower 2-24 h after irradiation non-significantly whereas between 3-10 days it did not differ from the controls. Radiation decreased the pineal melatonin content and its serum concentration 2 h after exposure and increased them significantly 1-3 days after irradiation. No changes in melatonin levels were found on postirradiation days 5-10. The corticosterone concentration was increased 2 h after exposure only. Local head irradiation changed neither thyrotropin nor thyroid hormone levels.
Male Wistar rats adapted to an artificial light-dark regimen (12 h light: 12 h darkness) were whole-body irradiated with a dose of 14.35 Gy of gamma rays. Irradiation, sham-irradiation and decapitation 30, 60 and 120 min after the exposure were performed between 2000 h and 0100 h in the darkness. The serotonin N-acetyltransferase activity (NAT), the concentration of melatonin, dopamine, norepinephrine and epinephrine were measured in the pineal gland. The serum levels of melatonin and corticosterone were also determined. Ionizing radiation did not change the activity of the key enzyme of melatonin synthesis, NAT, but decreased the concentration of pineal melatonin. The concentration of pineal dopamine and norepinephrine decreased 30 and 120 min after exposure, while the concentration of epinephrine was elevated 30 min after irradiation, though later it was markedly decreased. The serum melatonin level was not changed, but an increase in corticosterone level was observed. In the early period after the exposure, a decrease in pineal melatonin occurred, accompanied by a decrease in pineal catecholamines. On the contrary, in the phase of developed radiation injury the signs of increased melatonin synthesis were observed on days 3 and 4 after the exposure (Kassayova et al. 1993a). The underlying mechanisms require further research.