BACKGROUND: Predicting cardiovascular events remains challenging despite the range of known biomarkers. AIM: To establish relationships between various biochemical and functional parameters of the cardiovascular system. METHOD: The relationship between cardiovascular dys/function and various biomarkers was examined in 145 experimental rats half of which received isoprenaline 100 mg/kg s.c. to induce cardiac impairment. RESULTS: Serum concentration of cardiac troponin T (cTnT), a known marker of cardiac derangement, correlated strongly with degree of myocardial injury (e.g. calcium overload, stroke volume) but correlations between cTnT and oxidative stress parameters were weak (for glutathione and vitamin C) or not found (for serum vitamin E and plasma thiobarbituric acid reactive substances levels). Relationships between cTnT and other parameters were exponential with the exception of myocardial calcium, where a power function was found. CONCLUSIONS: Commonly used biomarkers of oxidative stress cannot reliably predict cardiovascular dys/function in experimental rats.

• MeSH
• biologické markery krev   MeSH
• kardiovaskulární nemoci * krev   patofyziologie   MeSH
• kardiovaskulární systém * metabolismus   patofyziologie   MeSH
• krysa rodu Rattus MeSH
• oxidační stres fyziologie   MeSH
• potkani Wistar MeSH
• tepový objem MeSH
• troponin T krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• troponin T MeSH

Positive effects of dexrazoxane (DEX) in anthracycline cardiotoxicity have been mostly assumed to be associated with its iron-chelating properties. However, this explanation has been recently questioned. Iron plays also an important role in the catecholamine cardiotoxicity. Hence in this study, the influence of DEX on a catecholamine model of acute myocardial infarction (100 mg/kg of isoprenaline by subcutaneous injection) was assessed: (i) the effects of an intravenous dose of 20.4 mg/kg were analyzed after 24 h, (ii) the effects were monitored continuously during the first two hours after drug(s) administration to examine the mechanism(s) of cardioprotection. Additional in vitro experiments on iron chelation/reduction and influence on the Fenton chemistry were performed both with isoprenaline/DEX separately and in their combination. DEX partly decreased the mortality, reduced myocardial calcium overload, histological impairment, and peripheral haemodynamic disturbances 24 h after isoprenaline administration. Continuous 2 h experiments showed that DEX did not influence isoprenaline induced atrioventricular blocks and had little effect on the measured haemodynamic parameters. Its protective effects are probably mediated by inhibition of late myocardial impairment and ventricular fibrillation likely due to inhibition of myocardial calcium overload. Complementary in vitro experiments suggested that iron chelation properties of DEX apparently did not play the major role.

• MeSH
• chelátory železa farmakologie   MeSH
• hemodynamika účinky léků   MeSH
• infarkt myokardu chemicky indukované   farmakoterapie   MeSH
• isoprenalin antagonisté a inhibitory   MeSH
• kardiotonika farmakologie   terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• potkani Wistar MeSH
• razoxan farmakologie   terapeutické užití   MeSH
• vápník metabolismus   MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chelátory železa MeSH
• isoprenalin MeSH
• kardiotonika MeSH
• razoxan MeSH
• vápník MeSH
• železo MeSH

Flavonoids have been demonstrated to possess miscellaneous health benefits which are, at least partly, associated with iron chelation. In this in vitro study, 26 flavonoids from different subclasses were analyzed for their iron chelating activity and stability of the formed complexes in four patho/physiologically relevant pH conditions (4.5, 5.5, 6.8, and 7.5) and compared with clinically used iron chelator deferoxamine. The study demonstrated that the most effective iron binding site of flavonoids represents 6,7-dihydroxy structure. This site is incorporated in baicalein structure which formed, similarly to deferoxamine, the complexes with iron in the stoichiometry 1:1 and was not inferior in all tested pH to deferoxamine. The 3-hydroxy-4-keto conformation together with 2,3-double bond and the catecholic B ring were associated with a substantial iron chelation although the latter did not play an essential role at more acidic conditions. In agreement, quercetin and myricetin possessing all three structural requirements were similarly active to baicalein or deferoxamine at the neutral conditions, but were clearly less active in lower pH. The 5-hydroxy-4-keto site was less efficient and the complexes of iron in this site were not stable at the acidic conditions. Isolated keto, hydroxyl, methoxyl groups or an ortho methoxy-hydroxy groups were not associated with iron chelation at all.

• MeSH
• chelátory železa chemie   MeSH
• deferoxamin chemie   MeSH
• flavanony chemie   MeSH
• flavonoidy chemie   MeSH
• flavony chemie   MeSH
• isoflavony chemie   MeSH
• koncentrace vodíkových iontů MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7-hydroxyflavanone MeSH Prohlížeč
• chelátory železa MeSH
• daidzein MeSH Prohlížeč
• deferoxamin MeSH
• flavanony MeSH
• flavone MeSH Prohlížeč
• flavonoidy MeSH
• flavony MeSH
• isoflavony MeSH

Epidemiological, as well as most in vivo, studies suggest that flavonoids have a positive influence on various cardiovascular diseases. Traditionally, these effects were only attributed to their antioxidant activity, which has been extensively studied. Apart from the direct antioxidant properties, which include direct reactive oxygen species scavenging activity and transient metal chelation, this review reports on many other effects that in pharmacologically achievable concentrations may also be responsible for their positive cardiovascular influence. These include direct inhibition of some radical-forming enzymes (xanthine oxidase, NADPH oxidase, and lipoxygenases), decreased platelet aggregation and leukocyte adhesion, and vasodilatory properties. For each of the aforementioned effects different structural features are necessary. Briefly, a catecholic B-ring is necessary for scavenging activity; hydroxyl groups in an ortho position, the 3-hydroxy-4-keto group, or the 5-hydroxy-4-keto group enable iron chelation; planar conformation with the 4-keto group and 2,3-double bond is essential for inhibition of leukocyte adhesion and platelet aggregation; specific hydroxy-methoxy ortho conformation in ring B is necessary for the inhibition of NADPH oxidase; and the 4-keto group is a requisite for vasodilatory action. This review shows that positive cardiovascular effects of flavonoids are achieved by various flavonoids via the interaction with different targets.

• MeSH
• aktivace trombocytů účinky léků   MeSH
• antioxidancia farmakologie   terapeutické užití   MeSH
• buněčná adheze účinky léků   MeSH
• enzymová indukce účinky léků   MeSH
• flavonoidy chemie   farmakologie   terapeutické užití   MeSH
• kardiovaskulární nemoci farmakoterapie   patofyziologie   MeSH
• lidé MeSH
• vazodilatace účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• flavonoidy MeSH

Coumarins are a large group of natural substances with diverse pharmacological properties that may predetermine some of them for the prevention and/or treatment of cardiovascular diseases and also other pathologies. Free iron participates in the production of reactive oxygen species (ROS) and plays an important role in the pathogenesis of cardiovascular diseases. Therefore, chelation of iron may attenuate some ROS consequences, but on the other hand, reduction of ferric ions to ferrous ones is unfavourable and leads to intensification of ROS production. In this study, we have examined the interaction of iron with coumarins which has been rarely analyzed. A series of naturally occurring and chemically synthesized 4-methylcoumarins were analyzed for their ferrous and total iron-chelating properties and compared with standard iron chelator deferoxamine. The iron chelation activity was assessed by a simple spectrophotometric approach based on the specific indicator for ferrous ions--ferrozine. The methodology was also extended for the measurement of total iron. Among the tested coumarins, ortho-dihydroxyderivatives were the most potent iron chelators and 7,8-dihydroxy-4-methylcoumarin even reached the efficiency of deferoxamine in neutral pH. However, these ortho-dihydroxycoumarins did not bind iron firmly in acidic conditions (e.g., in acute myocardial infarction) and, moreover, they reduced ferric ions that could lead to intensification of the Fenton chemistry. Other tested coumarins did not substantially chelate iron with the exception of ortho-diacetoxycoumarins. Conclusively, the use of iron-chelating coumarins in acidic conditions may be disadvantageous in contrast to neutral conditions.

• MeSH
• antioxidancia chemie   MeSH
• chelátory železa chemie   MeSH
• ferrozin chemie   MeSH
• koncentrace vodíkových iontů MeSH
• kumariny chemie   MeSH
• molekulární struktura MeSH
• železo chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• chelátory železa MeSH
• ferrozin MeSH
• kumariny MeSH
• železo MeSH

High levels of catecholamines are cardiotoxic and may trigger acute myocardial infarction (AMI). Similarly, the synthetic catecholamine isoprenaline (ISO) evokes a pathological state similar to AMI. During AMI there is a marked increase of free iron and copper which are crucial catalysts of reactive oxygen species formation. Rutin, a natural flavonoid glycoside possessing free radical scavenging and iron/copper chelating activity, may therefore be potentially useful in reduction of catecholamine cardiotoxicity as was previously demonstrated after its long-term peroral administration. Male Wistar:Han rats received rutin (46 or 11.5 mg kg(-1) i.v.) alone or with necrogenic dose of ISO (100 mg kg(-1) s.c.). Haemodynamic parameters were measured 24h after drug application together with analysis of blood, myocardial content of elements and histological examination. Results were confirmed by cytotoxicity studies using cardiomyoblast cell line H9c2. Rutin in a dose of 46 mg kg(-1) aggravated ISO-cardiotoxicity while the dose of 11 mg kg(-1) had no effect. These unexpected results were in agreement with in vitro experiments, where co-incubation with larger concentrations of rutin significantly augmented ISO cytotoxicity. Our results, in contrast to previous studies in the literature, suggest that the reported positive effects of peroral administration of rutin were unlikely to have been mediated by rutin per se but probably by its metabolite(s) or by some other, at this moment, unknown adaptive mechanism(s), which merit further investigation.

• MeSH
• agonisté adrenergních beta-receptorů farmakologie   MeSH
• cévní rezistence účinky léků   MeSH
• chelátory farmakologie   MeSH
• funkční vyšetření srdce MeSH
• glutathion metabolismus   MeSH
• interpretace statistických dat MeSH
• isoprenalin farmakologie   MeSH
• kardiomyocyty účinky léků   metabolismus   patologie   MeSH
• katecholaminy antagonisté a inhibitory   toxicita   MeSH
• krysa rodu Rattus MeSH
• minutový srdeční výdej účinky léků   MeSH
• myokard patologie   MeSH
• nemoci srdce chemicky indukované   patologie   prevence a kontrola   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rutin farmakologie   MeSH
• scavengery volných radikálů metabolismus   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté adrenergních beta-receptorů MeSH
• chelátory MeSH
• glutathion MeSH
• isoprenalin MeSH
• katecholaminy MeSH
• reaktivní formy kyslíku MeSH
• rutin MeSH
• scavengery volných radikálů MeSH