BACKGROUND: Predicting cardiovascular events remains challenging despite the range of known Biomarkers. AIM: To esta Blish 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 thio Bar Bituric acid reactive su Bstances 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 relia Bly predict cardiovascular dys/function in experimental rats.
- MeSH
- Biomarkers blood MeSH
- Cardiovascular Diseases * blood physiopathology MeSH
- Cardiovascular System * metabolism physiopathology MeSH
- Rats MeSH
- Oxidative Stress physiology MeSH
- Rats, Wistar MeSH
- Stroke Volume MeSH
- Troponin T blood MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov'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
- Iron Chelating Agents pharmacology MeSH
- Hemodynamics drug effects MeSH
- Myocardial Infarction chemically induced drug therapy MeSH
- Isoproterenol antagonists & inhibitors MeSH
- Cardiotonic Agents pharmacology therapeutic use MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Myocardium metabolism pathology MeSH
- Rats, Wistar MeSH
- Razoxane pharmacology therapeutic use MeSH
- Calcium metabolism MeSH
- Iron metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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
- Iron Chelating Agents chemistry MeSH
- Deferoxamine chemistry MeSH
- Flavanones chemistry MeSH
- Flavonoids chemistry MeSH
- Flavones chemistry MeSH
- Isoflavones chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Binding Sites MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Předložený článek poukazuje na významné preventivní a/nebo kurativní účinky oddenku kurkumy či kurkuminu, které byly zjištěny u modelů experimentálních zvířat u množství nemocí, zahrnující aterosklerózu, rakovinu, diabetes, respiratorní, jaterní, pankreatické, intestinální a žaludeční nemoci, neurodegenerativní a oční nemoci. Zároveň uvádí i možné interakce této drogy s ostatními léčivy.
The present article highlights significant preventive and/or curative effects of Rhizoma curcumae, or curcumin, that have been found in experimental animal models in a number of conditions, including atherosclerosis, cancer, diabetes, respiratory, hepatic, pancreatic, intestinal and gastric diseases, neurodegenerative conditions and eye diseases. It also deals with possible interactions of this drug with other medications.
- Keywords
- Curcuma xanthorrhiza, Curcuma longa, vedlejší účinky,
- MeSH
- Atherosclerosis drug therapy prevention & control MeSH
- Diabetes Mellitus drug therapy prevention & control MeSH
- Financing, Organized MeSH
- Cucurbitacins pharmacology adverse effects therapeutic use MeSH
- Curcumin MeSH
- Neoplastic Processes MeSH
- Digestive System Diseases drug therapy MeSH
- Lung Diseases drug therapy prevention & control MeSH
- Food Coloring Agents chemistry therapeutic use MeSH
- Dietary Supplements 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
- Platelet Activation drug effects MeSH
- Antioxidants pharmacology therapeutic use MeSH
- Cell Adhesion drug effects MeSH
- Enzyme Induction drug effects MeSH
- Flavonoids chemistry pharmacology therapeutic use MeSH
- Cardiovascular Diseases drug therapy physiopathology MeSH
- Humans MeSH
- Vasodilation drug effects MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review 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.
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
- Adrenergic beta-Agonists pharmacology MeSH
- Vascular Resistance drug effects MeSH
- Chelating Agents pharmacology MeSH
- Financing, Organized MeSH
- Heart Function Tests MeSH
- Glutathione metabolism MeSH
- Data Interpretation, Statistical MeSH
- Isoproterenol pharmacology MeSH
- Myocytes, Cardiac metabolism pathology drug effects MeSH
- Catecholamines antagonists & inhibitors toxicity MeSH
- Rats MeSH
- Cardiac Output drug effects MeSH
- Myocardium pathology MeSH
- Heart Diseases chemically induced pathology prevention & control MeSH
- Rats, Wistar MeSH
- Reactive Oxygen Species metabolism MeSH
- Rutin pharmacology MeSH
- Free Radical Scavengers metabolism MeSH
- Organ Size drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- MeSH
- Animal Experimentation MeSH
- Financing, Organized MeSH
- Flavonoids administration & dosage pharmacology MeSH
- Isoproterenol diagnostic use toxicity MeSH
- Cardiotoxins diagnostic use toxicity MeSH
- Cardiovascular Diseases etiology drug therapy MeSH
- Catecholamines diagnostic use toxicity MeSH
- Rats, Wistar MeSH
- Reactive Oxygen Species pharmacology MeSH
- Rutin diagnostic use MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Abstracts MeSH
