Biomedical subjects

M Stefek

Publications and source records attributed to M Stefek.

At least 19 recordsLinked to original sources

PubMed2006

Effect of the pyridoindole antioxidant stobadine on the cardiac Na(+),K(+)-ATPase in rats with streptozotocin-induced diabetes.

In the present study we examined the effect of dietary supplementation with the pyridoindole antioxidant stobadine on functional properties of the cardiac Na(+),K(+)-ATPase in diabetic rats. Diabetes lasting sixteen weeks which was induced by a single i.v. dose of streptozotocin (55 mg x kg(-1)) was followed by decrease in the enzyme activity. Evaluation of kinetic parameters revealed a statistically significant decrease in the maximum velocity (Vmax) (32% for ATP-activation, 33% for Na(+)-activation), indicating a diabetes-induced diminution of the number of active enzyme molecules in cardiac sarcolemma. The ATP-binding properties of the enzyme were not affected by diabetes as suggested by statistically insignificant changes in the value of Michaelis-Menten constant, K(M (ATP)). On the other hand, the affinity to sodium decreased as suggested by 54% increase in the K(M (Na+)) value. This impairment in the affinity of the Na(+)-binding site together with decreased number of active Na(+),K(+)-ATPase molecules are probably responsible for the deteriorated enzyme function in hearts of diabetic animals. Administration of stobadine to diabetic rats dramatically improved the function of cardiac Na(+),K(+)-ATPase with regard to Na(+)-handling, as documented by statistically significant elevation of Vmax by 66 and 47% decrease in K(M (Na+)). Our data suggest that stobadine may prevent the diabetes-induced deterioration of cardiac Na(+),K(+)-ATPase, thus enabling to preserve its normal function in regulation of intracellular homeostasis of Na(+) and K(+) ions.

Animals↗

PubMed2006

Changes in the function and ultrastructure of vessels in the rat model of multiple low dose streptozotocin-induced diabetes.

In this study we investigated functional changes in the femoral artery and ultrastructural alterations in mesenteric vessels and capillaries in the rat model of multiple low dose streptozotocin (STZ)-induced diabetes. Participation of oxidative stress in this model of diabetes was established by studying the effect of the pyridoindole antioxidant stobadine (STB) on diabetes-induced impairment. Experimental diabetes was induced by i.v. bolus of STZ (20 mg/kg) given for three consecutive days to male rats. At the 12(th) week following STZ administration, the animals revealed typical signs of diabetes, such as polyphagia, polydypsia and polyuria. There was no weight gain in the diabetic groups throughout the experiment. No exitus occurred in any group. Diabetes was characterised with high levels of plasma glucose, no significant changes in lipid metabolism, decreased serum levels of glutathione, increased serum levels of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAGA), injured endothelial relaxant capacity of the femoral artery and alterations in ultrastructure of mesenteric arteries and capillaries. Antioxidant STB in the dose of 25 mg/kg body weight i.p. (5 times per week) did not influence glucose levels, however, it mitigated biochemical, functional and ultrastructural changes induced by diabetes, suggesting a role of reactive oxygen species in diabetes-induced tissue damage.

Animals↗

PubMed2005

Oxidative modification of rat eye lens proteins by peroxyl radicals in vitro: protection by the chain-breaking antioxidants stobadine and Trolox.

In an attempt to model the processes of free radical-mediated cataractogenesis, we investigated the oxidative modification of rat eye lens proteins by peroxyl radicals generated by thermal decomposition of 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH) under aerobic conditions. When incubated with AAPH, the soluble eye lens proteins precipitated in a time-dependent manner. The insolubilisation was accompanied by the accumulation of protein free carbonyls and the diminution of sulfhydryls, yet the processes were shifted in time. The SDS-PAGE analysis of the AAPH-treated proteins revealed the presence of high molecular weight cross-links and, to a lesser extent, fragments. The aggregation and cross-linking of proteins along with the generation of free carbonyls was significantly inhibited by the chain-breaking antioxidants stobadine and Trolox. On the other hand, the AAPH-initiated sulfhydryl consumption was much less sensitive to the antioxidants studied. The results point to a complex mechanism of peroxyl-radical-mediated modification of eye lens proteins with implications for cataract development and they indicate a potentially protective role of antioxidants.

Aerobiosis↗

PubMed2005

Reactive oxygen species mediate abnormal contractile response to sympathetic nerve stimulation and noradrenaline in the vas deferens of chronically diabetic rats: effects of in vivo treatment with antioxidants.

Previous studies suggest that a link exists between increased oxidative stress and diabetic neuropathy. Moreover, antioxidants may protect neurones from the degenerative effects of reactive oxygen species. In our study, we used streptozotocin (STZ)-diabetic rats in a 8-month chronic diabetes model to study the effects of in vivo treatment with stobadine (ST), a pyridoindole antioxidant, and vitamin E. STZ-diabetic rats were treated with ST (24.7 mg/kg/day), vitamin E (D,L-alpha-tocopheryl acetate, 400-500 IU/kg/day) or ST plus vitamin E through an intra-oral catheter for a 8-month period beginning 10 days after STZ injection. Blood glucose and HbA1c levels were increased in diabetic rats by about 400 and 100%, respectively. Antioxidant treatment significantly decreased haemoglobin glycosylation (P < 0.05). We also determined the effects of chronic diabetes on sympathetic neurotransmission by measuring the contractility of isolated vas deferens. Furthermore, we investigated contractions elicited by electrical field stimulation (EFS) (1-64 Hz) which were significantly decreased in diabetic rats when compared with control rats. Treatment with ST or vitamin E alone partly enhanced the amplitude of the contractions induced by EFS, but a combination of ST and vitamin E treatment showed no additional effects. Contractile response of the vas deferens to exogenous noradrenaline, was increased in diabetic rats when compared with control rats. While the addition of vitamin E alone had no effect, ST completely returned noradrenaline-induced contractions to basal levels. The tension induced by 120 mm KCl was not statistically different among the experimental groups. In normal rats, EFS-induced contractions were significantly inhibited by pyrogallol (10(-4) m), a free-radical generator. Percentage inhibition of pyrogallol on EFS (32 Hz)-induced contractions in ring sections was 48 +/- 5.8 in control, 75 +/- 5.5 in untreated-diabetic, 54 +/- 2.7 in ST-treated diabetic, and 58 +/- 4.7 in vitamin E-treated diabetic rats. Combining both ST and vitamin E treatment had the same effects as each antioxidant alone with a percent inhibition of 48 +/- 6.8. These results are consistent with the degenerative changes seen in sympathetic nerves and the abnormal function observed in chronically diabetic rats, leading to a decrease in EFS response and an increase in response to adrenergic agonists in the vas deferens. Furthermore, we demonstrated that reactive oxygen species are responsible for impaired sympathetic neurotransmission and abnormal function of diabetic vas deferens, and that a combination of antioxidants may be better for the therapy of reproductive system disabilities in male diabetics.

Animals↗

PubMed2005

Temporal relationship between lens protein oxidation and cataract development in streptozotocin-induced diabetic rats.

We compared the progression of lens opacification with the time course of oxidation of lens proteins under conditions of streptozotocin-induced experimental diabetes in rats. By the end of the 17th week, approx. 50% of the diabetic animals developed mature cataracts. During the following month, 95% of the eyes in the diabetic group became cataractous. In the course of lens opacification we observed a time-dependent increase in the content of protein carbonyls and decrease in the concentration of protein sulfhydryls in the lenses of diabetic animals. Significantly higher protein carbonyl (p<0.01) and lower protein sulfhydryl (p<0.001) content was found in lenses with the advanced stage of cataract when compared with the diabetic lenses still transparent. We showed that the values of protein carbonyls exceeding 1.2 nmol/mg protein and of sulfhydryls falling below 60 nmol/mg protein corresponded to an approximately 50% incidence of mature cataract development. At the end of the 34th week, when all lenses of diabetic rats became cataractous, the corresponding values of protein carbonyls and sulfhydryls were 2.5 nmol/mg protein and 27 nmol/mg protein, respectively. The main finding of this study is the disclosure of quantitative relationship between the degree of protein oxidation and the rate of advanced cataract development in the widely used model of streptozotocin-induced experimental diabetes in rats.

Animals↗

PubMed2004

Effect of the pyridoindole antioxidant stobadine on sodium handling of renal Na,K-ATPase in rats with streptozotocin-induced diabetes.

Overload of reactive oxygen species during diabetes is known to impair cellular homeostasis and to promote deterioration of membrane function in the organism. The aim of the present study was to examine the effect of dietary supplementation with the pyridoindole atioxidant stobadine on functional properties of the renal Na, K-ATPase in diabetic rats. After 16 weeks of streptozotocin-induced diabetes (single intravenous dose of streptozotocin; 55 mg/kg), a significant inhibition (by 35%-42%) of the enzyme was observed throughout the range of NaCl 2-100 mmol/l, probably as an event of altered functional properties of Na,K-ATPase, suggested by the 42% decrease of the V(max) value. Administration of 0.05% (w/w) stobadine in the diet dramatically improved the function of renal Na,K-ATPase in diabetic rats with regard to sodium handling, as suggested by significant stimulation (by 104%-77% in accordance with increasing concentration of NaCl) of the enzyme over the whole NaCl concentration range investigated. This stimulatory effect was accompanied by an increase of V(max) value to the level of nondiabetic rats on standard diet. In conclusion, stobadine was found to antagonise the negative effects of diabetes on the renal Na,K-ATPase, preserving its normal function in regulation of intracellular homeostasis of Na(+) and K(+) ions.

Animals↗

PubMed2003

Involvement of L-arginine-nitric oxide system in the response of isolated trachea to reactive oxygen species.

The aim of this study was to investigate the effect of reactive oxygen species (ROS), generated by electrolysis of Krebs-Henseleit solution (GE-KHS), on isolated guinea pig trachea and to assess the possible involvement of nitric oxide (NO) in the observed effects. The isolated trachea was superfused in GE-KHS, generating H2O2 and hypochlorous acid (HOCl), both of which slowly increased in the organ bath and reached final stable concentrations of 42 and 63 microM, respectively, at the rate of 20 ml/min(-1), and 261 and 245 microM, respectively, at the rate of 5 ml/min(-1). ROS GE-KHS-induced relaxation of tracheal rings was preceded by a small transient contraction in 40% and 65% of experiments when tracheal rings were superfused at the rate of 20 ml/min(-1) and 5 ml/min(-1), respectively. Removal of tracheal epithelium abolished the relaxation of the trachea induced by ROS GE-KHS and unmasked or potentiated trachealis contraction. The ROS GE-KHS-induced changes in trachealis tension were accompanied by an increase in thiobarbituric acid reactive substances (TBARS) and a decrease in nonprotein (NP) thiols in the trachea. These changes were inhibited by treatment with the antioxidant N-acetylcysteine (100 microM). Pretreatment of tracheal rings with the inhibitor of NO synthase (NOS) N(omega)-nitro-L-arginine (L-NOARG; 100 microM) for 20 min prior to exposure to ROS GE-KHS decreased the ROS GE-KHS-induced relaxation. When L-NOARG (100 microM) was present in the superfusing solution, not only 20 min before but also during superfusion with ROS GE-KHS, the evoked trachealis relaxation was reduced in the first 15 min but was enhanced in the 30th min. This late enhancement of relaxation was accompanied by a 12-fold increase in nitric oxide metabolites (NO(x)). ROS GE-KHS-induced elevation of TBARS levels in the trachea was decreased to 63% by pretreatment with L-NOARG (100 microM). Elevation of TBARS levels induced by incubation of brain liposomes with a hydroxyl radical generating system was decreased to 90% by L-NOARG (10, 100 microM), while the antioxidant stobadine (100 microM) nearly completely inhibited the evoked lipid peroxidation. In comparison with Trolox, L-NOARG exerted a slight scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl radical. The presence of L-arginine and D-arginine in the superfusion fluid for 15-20 min before and during exposure of the trachea to ROS GE-KHS inhibited trachealis relaxation. Results indicate that epithelium derived NO may participate in the response of guinea pig trachea to ROS GE-KHS. The presence of L-NOARG in the bathing fluid during superfusion with ROS GE-KHS gave rise to NO(x), with relaxing activity. L- and D-arginine induced an inhibition of the relaxatory response to ROS GE-KHS and partially prevented a ROS-induced decrease in NP thiols. The involvement of the small antioxidant effects of L-NOARG and L- and D-arginine in the above mentioned actions of L-NOARG and L-arginine requires additional investigation.

Acetylcysteine↗

PubMed2003

Cardiac effects of endothelin-1 (ET-1) and related C terminal peptide fragment: increased inotropy or contribution to heart failure?

The contrasting pattern of cardiac inotropy induced by human peptide endothelin-1 (ET-1) has not been satisfactorily explained. It is not clear whether ET-1 is primarily responsible for increased myocardial ET-1 expression and release with resultant inotropic effects, or for the induction of myocardial hypertrophy and heart failure. There are at least two subtypes of endothelin receptors (ET(A) and ET(B)) and the inotropic effects of ET-1 differ depending on the receptor involved. Along with some other groups, we reported significant subtype-ET(B) endothelin receptor down-regulation in human cardiac cells preincubated with endothelin agonists (Drímal et al. 1999, 2000). The present study was therefore designed to clarify the subtype-selective mechanisms underlying the inotropic response to ET-1 and to its ET(B)-selective fragment (8-21)ET-1 in the isolated rat heart. The hearts were subjected to (1-21)ET-1 and to (8-21)ET-1, or to 30 min of stop-flow ischemia followed by 40 min of reperfusion, both before and after selective blockade of endothelin receptors. The present study revealed that both peptides, ET-1 and its (8-21)ET-1 fragment, significantly reduced coronary blood flow in nmolar and higher concentrations. The concomitant negative inotropy and chronotropy were marked after ET-1, while the infusion of the ET-1(8-21) fragment produced a slight but significant positive inotropic effect. Among the four endothelin antagonists tested in continuous infusion only the non-selective PD145065 and ET(B1/B2) selective BQ788 (in molar concentrations) slightly reduced the early contractile dysfunction of the heart induced by ischemia, whereas ET(A)-selective PD155080 partially protected the rat heart on reperfusion.

Amino Acid Sequence↗

PubMed2002

Structural aspects of antioxidant activity of substituted pyridoindoles.

Stobadine and its two structural analogues, dehydrostobadine and N-acetylated stobadine were used to examine how structural alteration in the close proximity of the indolic nitrogen would influence the antioxidant activity of the substituted pyridoindoles. The compounds were tested for their efficiency to scavenge stable free radicals of alpha,alpha'-diphenyl-beta-picrylhydrazyl as well as for their ability to prevent 2,2'-azobis-(2-amidinopropane)hydrochloride induced peroxidation of dioleoyl phosphatidylcholine liposomes. The results proved that the substituted pyridoindoles can act as potent scavengers of peroxyl radicals both in aqueous and lipid phases, the antioxidant activity being comparable with that of Trolox. Structural changes in the proximity of the indolic nitrogen were found crucial for the radical scavenging efficiency: aromatisation of the pyridoindole skeleton in dehydrostobadine lowered the antioxidant activity, while acetylation of the indolic nitrogen completely abolished the ability to scavenge peroxyl radicals. The results are in agreement with the notion that the antioxidant activity of stobadine and of the related pyridoindoles may be mediated via the indolic nitrogen centre. When stobadine and Trolox were present simultaneously in liposomal incubations, Trolox spared stobadine in a dose-dependent manner; a direct interaction of Trolox with stobadinyl radical appears to be a plausible explanation with possible consequences for the antioxidant capacity of stobadine under in vivo conditions, where re-cycling of stobadine by vitamin E might occur.

Antioxidants↗

PubMed2002

L-arginine reduces structural remodeling in the diabetic rat myocardium.

Metabolism, monitored via in situ catalytic enzyme histochemistry and fine structure, was studied in the myocardium of chronic diabetic male Wistar rats administered L-arginine (12.8 mg/100 g/day) for 24 weeks. Diabetes was induced with a single i.v. injection of 55 mg/kg streptozotocin. After 6 months, the tissue of the left ventricle was processed for electron microscope examination and transmural tissue blocks were frozen for enzyme histochemistry. In diabetic myocardium, heterogeneous ischemia-like subcellular alterations of cardiomyocytes and capillaries were observed, together with interstitial fibrosis. This structural remodeling was accompanied by significantly decreased activity of endothelial nitric oxide synthase (NOS) and heterogeneously decreased activities of glycogen phosphorylase (GlPh), hydroxybutyrate dehydrogenase (HBDH) and adenosine triphophatases (ATPases) throughout the myocardium. In arginine-treated diabetic rats, there was evidence of protected structural integrity of endothelial cells and attenuated structural disturbances of cardiomyocytes. This was associated with the markedly preserved histochemical activities of all detected enzymes in comparison with nontreated diabetic rats (NOS 98.7 +/- 10.5% vs. 35.4 +/- 4.1%; ATPases 82.7 +/- 9.1% vs. 69.3 +/- 5.2%; GlPh 65.2 +/- 8.3% vs. 45.5 +/- 3.8%; HBDH 68.9 +/- 8.5% vs. 44.1 +/- 6.7% of control values). The results indicate that long-term supplementation of L-arginine may account for the reduction of diabetes-induced myocardial structural remodeling.

Animals↗

PubMed2002

The pyridoindole antioxidant stobadine attenuates albuminuria, enzymuria, kidney lipid peroxidation and matrix collagen cross-linking in streptozotocin-induced diabetic rats.

The aim of the present study was to investigate the effect of dietary supplementation with the pyridoindole antioxidant stobadine on kidney status and function in streptozotocin-induced diabetic rats. Diabetic male Wistar rats were fed a standard diet for 32 weeks or a diet supplemented with stobadine (0.05% w/w). The diabetic state was characterized by significantly elevated plasma levels of glucose, HbA1c and urea, severe reduction of total body weight and relatively enlarged kidneys. Elevated levels of conjugated dienes were recorded in the diabetic kidney confirming the presence of oxidative stress in diabetic animals. All diabetic rats showed marked proteinuria and albuminuria along with elevated excretion of the enzyme N-acetyl-beta-D-glucosaminidase. Long-term treatment of diabetic animals with stobadine significantly reduced total proteinuria, albuminuria and enzymuria, yet left the overall physical and glycemic status unaffected. It reduced oxidative damage of kidney tissue as shown by decreased conjugated diene level, and decreased matrix collagen cross-linking, as indicated by decreased breaking time values of rat tail tendons. These beneficial effects of stobadine, supported also by histological findings, may be brought about by virtue of the combination of its antioxidant potential with other effects, e.g., the postulated cholesterol-lowering ability or its ability to alter vascular reactivity and reduce the vascular tone.

Acetylglucosaminidase↗

PubMed2001

Dietary supplementation of the pyridoindole antioxidant stobadine reduces vascular impairment in streptozotocin-diabetic rats.

We studied the influence of hyperglycemia lasting 1, 4, 6 and 8 months on the reactivity and ultrastructure of the aorta in Wistar rats. Moreover, the effect of the pyridoindole antioxidant stobadine ((-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole) on the changes induced by the 8-month hyperglycemia were studied. Hyperglycemia was induced by streptozotocin (STZ, 55 mg/kg i.v.). In the functional study, responses to KCl, acetylcholine (ACh), noradrenaline (NA) and hydrogen peroxide were evaluated under isometric conditions. The first changes in aortic reactivity started after 1 month of hyperglycemia and were exhibited by significantly increased NA-induced contractions. Relaxant responses to acetylcholine were decreased, although not significantly. Prolongation of hyperglycemia to 4, 6 and 8 months did not cause any additional significant changes in responsiveness to NA. Decreased ACh-induced relaxation and increased contractile responses to H2O2 were observed in month 4. The functional responses were not substantially deteriorated by prolongation of hyperglycemia to 6 and 8 months. Ultrastructural examination of the diabetic aorta showed disturbances in normal tissue organization. An 8-month supplementation of stobadine in diabetic rats resulted in the protection of aortic function as well as its ultrastructure. These results suggest that abnormalities occurring in the aorta of diabetic rats might result from the damaging effects of oxygen free radicals.

Animals↗

PubMed2001

Adaptive changes of antioxidant status in development of experimental diabetes.

BACKGROUND: In clinical and experimental research, attention is paid to the role of antioxidant defense systems in the prevention of diabetic complications. Little information is available about regulation of the endogenous level of antioxidants in the state of chronic oxidative stress in relation to the development of diabetes, and particularly about coenzyme Q as one of the most important endogenous antioxidants with an irreplaceable function in mitochondrial bioenergetics. PURPOSE: To examine changes in concentrations of two important lipophilic antioxidants, coenzyme Q9 and alpha-tocopherol, in rat tissues during the development of experimental diabetes. METHODS: Experimental diabetes in male Wistar rats, was induced by streptozotocin in the dose of 55 mg/kg intravenously. Coenzyme Q9 (CoQ9) and alpha-tocopherol (alpha-toc.) were determined in myocardial and skeletal muscles and in kidney tissue after 1, 6 and 8 months of diabetes duration by the method of high-performance liquid chromatography. RESULTS: Myocardial CoQ9 content increased progressively in the course of diabetes development by 14, 29 and 61%, while in skeletal muscles and kidney, the increases were not dependent on the duration of diabetes. The content of alpha-toc. increased in the myocardium after 8 months of diabetes duration, in kidney tissue and skeletal muscles, it did not change in comparison with control rats. CONCLUSIONS: An increased content of the lipophilic antioxidants coenzyme Q9 and alpha-tocopherol in tissues of diabetic rats is regarded as an adaptation of the antioxidant defense system to chronic oxidative stress. The exact mechanisms of accumulation of these antioxidants in diabetic tissues could be elucidated by studies investigating their relation to changes in lipid content and to the total of bioenergetic and antioxidant capacities. (Fig. 3, Ref. 25.)

Animals↗

PubMed2000

p-Dimethylaminobenzaldehyde-reactive substances in tail tendon collagen of streptozotocin-diabetic rats: temporal relation to biomechanical properties and advanced glycation endproduct (AGE)-related fluorescence.

In the present work, pepsin digests of tail tendons from streptozotocin-diabetic rats were found to contain material that reacted rapidly at room temperature with p-dimethylaminobenzaldehyde (Ehrlich's reagent) to give an adduct with an absorbance spectrum characteristic of the Ehrlich chromogen of pyrrolic nature determined in ageing collagens. A significant correlation of the Ehrlich adduct with tendon mechanical strength and collagen fluorescence characteristic of advanced glycation endproducts was observed. Collagen content of the Ehrlich-positive material was found to be significantly elevated in tendons of diabetic rats compared with age-matched healthy controls. The results indicate that the p-dimethylaminobenzaldehyde-reactive pyrrole moieties may contribute to the increased cross-linking of diabetic matrix collagen. Profound inhibitory effect of aminoguanidine was observed, underlining the role of non-enzymatic mechanisms of advanced glycation in pyrrolisation and cross-linking of collagen exposed to hyperglycaemia. It is hypothesised that quantification of the p-dimethylaminobenzaldehyde-reactive material in matrix collagen may provide a tissue measure of integrated hyperglycaemia over prolonged periods of time. Further research is to assess the significance of p-dimethylaminobenzaldehyde-reactive substances in diabetic collagen tissues and to reveal their relationship to enzyme-mediated physiological pyrrolisation of ageing collagens.

Animals↗

PubMed2000

Effect of dietary supplementation with the pyridoindole antioxidant stobadine on antioxidant state and ultrastructure of diabetic rat myocardium.

Consistent with the postulated role of oxidative stress in the etiology of late diabetic complications, pharmacological interventions based on biological antioxidants have been suggested. The aim of the present study was to investigate the effect of dietary supplementation with the pyridoindole antioxidant stobadine on the myocardial antioxidant status and ultrastructure of streptozotocin-diabetic rats. Diabetic male Wistar rats were fed for 32 weeks a standard diet or a diet supplemented with stobadine (0.05% w/w). Control rats received a standard diet or stobadine-supplemented diet (0.16% w/w). Plasma levels of glucose, cholesterol and triglycerides were increased significantly by diabetes. Activities of superoxide dismutase and catalase were markedly elevated in the diabetic myocardium. Myocardial levels of conjugated dienes increased after eight months of diabetes, in spite of significantly increased myocardial alpha-tocopherol and coenzyme Q9 content. The long-term treatment of diabetic animals with stobadine (i) reduced plasma cholesterol and triglyceride levels yet left the severe hyperglycemia unaffected, (ii) reduced oxidative damage of myocardial tissue as measured by conjugated dienes, (iii) reversed myocardial levels of alpha-tocopherol and coenzyme Q9 to near control values, (iv) reduced elevated activity of superoxide dismutase in the diabetic myocardium, and (v) attenuated angiopathic and atherogenic processes in the myocardium as assessed by electron microscopy examination. These results are in accordance with the postulated prooxidant role of chronic hyperglycemia and provide further evidence that development of pathological changes in diabetic myocardium is amenable to pharmacological intervention by biological antioxidants.

Animals↗

PubMed2000

Serum ferritin levels in subjects at high risk of atherosclerosis.

Serum ferritin levels were determined in a group of 148 subjects drawn from a community study who were found to be at high risk of atherosclerosis (evaluated on the basis of the following data: levels of non-HDL cholesterol, arterial pressure, smoking status, cardiovascular or cerebrovascular disease in a subject's history, diabetes mellitus, a positive family predisposition to, or accumulation of the above factors) and compared with the levels obtained in a control group of 148 examined age- and sex-matched subjects from the same community with non-significant risk factors. Mean serum ferritin levels were higher in the whole risk group and in the subgroups of risk men and postmenopausal women than in the corresponding controls (the whole risk group: 263.4 +/- 218.5 micrograms/l vs. 198.3 +/- 179.5 micrograms/l, p < 0.05; the subgroup of men 361.8 +/- 235.7 micrograms/l vs. 286.4 +/- 194.6 micrograms/l, p < 0.05 and the subgroup of postmenopausal women 184.1 +/- 143.1 vs. 126.7 +/- 108.4 micrograms/l, p < 0.05).

Adult↗

PubMed1999

Reactive oxygen species induced smooth muscle responses in the intestine, vessels and airways and the effect of antioxidants.

Numerous experimental data confirm the importance of reactive oxygen species (ROS) in physiological activities of smooth muscles and in the pathogenesis of various diseases with altered function of smooth muscles. The present study shows that smooth muscles of the intestine, airways and vessels, as well as their epithelium, endothelium and innervations, might be important targets of the ROS action. We demonstrated differences among the actions of various ROS (endogenous, exogenous, produced enzymatically, non-enzymatically) as well as among their actions in different smooth muscle tissues. Our results indicate that ROS are involved in changes in muscle tone, membrane conductance, calcium homeostasis, calcium-dependent processes, as well as in eicosanoid and nitric oxide metabolism. The effects of antioxidative enzymes (superoxide dismutase, catalase), of several drugs of natural origin (e.g. Kampo Medicines) and synthetic agents (e.g. stobadine, nitrosopine, ACE inhibitors) suggest that smooth muscle tissues are useful models to study ROS action and drug intervention in ROS induced injuries.

Animals↗

PubMed1999

Oxidative modification of serum albumin in an experimental glycation model of diabetes mellitus in vitro: effect of the pyridoindole antioxidant stobadine.

Under conditions of an experimental in vitro glycation model, the pyridoindole antioxidant stobadine significantly inhibited glycation-related fluorescence changes of bovine serum albumin as well as the yield of 2,4-dinitrophenylhydrazine-reactive carbonyls with an efficacy comparable to that of the reference antioxidants Trolox C and 2-keto-4-methiolbutyric acid, and more efficiently than did aminoguanidine. Since stobadine did not affect the covalent binding of glucose, the protective effect may be explained by the ability of the drug to eliminate free radical intermediates of glyco-oxidation reactions, operative after the preceding glycation steps.

Animals↗