Muscle regeneration is regulated through interaction between muscle and immune cells. Studies showed that treatment with supra-physiological doses of Non-Steroidal Anti-Inflammatory Drug (NSAID) abolished inflammatory signaling and impaired muscle recovery. The present study examines the effects of pharmacologically-relevant NSAID treatment on muscle regeneration. C57BL/6 mice were injected in the tibialis anterior (TA) with either PBS or cardiotoxin (CTX). CTX-injected mice received ibuprofen (CTX-IBU) or were untreated (CTX-PLAC). After 2 days, Il-1beta and Il-6 expression was upregulated in the TA of CTX-IBU and CTX-PL vs. PBS. However, Cox-2 expression and macrophage infiltration were higher in CTX-PL vs. PBS, but not in CTX-IBU. At the same time, anabolic markers were higher in CTX-IBU vs. PBS, but not in CTX-PL. Nevertheless, ibuprofen did not affect muscle mass or muscle fiber regeneration. In conclusion, mild ibuprofen doses did not worsen muscle regeneration. There were even signs of a transient improvement in anabolic signaling and attenuation of inflammatory signaling.

• MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• hojení ran účinky léků   fyziologie   MeSH
• ibuprofen farmakologie   MeSH
• kardiotoxiny toxicita   MeSH
• kosterní svaly účinky léků   zranění   patologie   fyziologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• regenerace účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antitumorózní látky toxicita   MeSH
• časná detekce nádoru MeSH
• karcinogeny toxicita   MeSH
• kardiotoxicita * diagnóza   etiologie   MeSH
• kardiotoxiny toxicita   MeSH
• kritické orgány MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kongresy MeSH
• zprávy MeSH

Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (PKA) to accelerate aging by inhibiting transcription factors Msn2/4. Here, we show that fasting or glucose restriction (GR) regulate PKA and AMP-activated protein kinase (AMPK) to protect against DXR in part by activating the mammalian Msn2/4 ortholog early growth response protein 1 (EGR1). Increased expression of the EGR1-regulated cardioprotective peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart tissue may also contribute to DXR resistance. Our findings suggest the existence of a glucose-PKA pathway that inactivates conserved zinc finger stress-resistance transcription factors to sensitize cells to toxins conserved from yeast to mammals. Our findings also describe a toxic role for drugs widely used in cancer treatment that promote hyperglycemia and identify dietary interventions that reverse these effects.

• MeSH
• antitumorózní látky farmakologie   MeSH
• atriální natriuretický faktor metabolismus   MeSH
• časové faktory MeSH
• cytoprotekce účinky léků   MeSH
• dexamethason farmakologie   MeSH
• dieta MeSH
• fyziologický stres účinky léků   MeSH
• glukosa farmakologie   MeSH
• hyperglykemie patologie   MeSH
• kardiotoxiny toxicita   MeSH
• metformin farmakologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• natriuretický peptid typu B metabolismus   MeSH
• omezení příjmu potravy metabolismus   MeSH
• protein 1 časné růstové odpovědi metabolismus   MeSH
• proteinkinasy aktivované AMP metabolismus   MeSH
• proteinkinasy závislé na cyklickém AMP metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The synthetic catecholamine isoprenaline (ISO) has been used as an inductor in the acute myocardial infarction model for more than a half century. Despite the fact that many articles were published on this topic, precise early haemodynamic pathology remains unknown. Acute haemodynamic changes were measured in rats; first, in preliminary experiments by the thermodilution method; and second, in main experiments continuously for 2 h using a Millar catheter. Animals received saline or ISO in the cardiotoxic dose (100 mg/kg, subcutaneously). Also, additional experiments were performed with salbutamol in order to evaluate the role of β(2)-receptors. ISO caused a rapid, within 1 min, approximately 40% decrease in arterial blood pressures, 30% increase in the heart rate, and 30% decrease in the stroke volume. Within the first 2 min, the changes were followed by decreases in afterload (-40%), preload (-10%), diastolic relaxation (-50%), diastolic filling (-40%), and a marked, but short-term, increase in the left ventricle contractility (+100%). Ejection fraction did not significantly change, suggesting diastolic dysfunction. Salbutamol, with the exception of diastolic pressure and afterload, did not substantially influence other parameters. In conclusion, this study demonstrated that diastolic dysfunction precedes systolic dysfunction and β(2)-receptor stimulation alone is not sufficient for an early induction of diastolic dysfunction.

• MeSH
• agonisté adrenergních beta-receptorů toxicita   MeSH
• funkce levé komory srdeční účinky léků   MeSH
• hemodynamika účinky léků   MeSH
• isoprenalin toxicita   MeSH
• kardiotoxiny toxicita   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• potkani Wistar MeSH
• srdce účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• dospělí MeSH
• kardiotoxiny škodlivé účinky   toxicita   MeSH
• kardiovaskulární nemoci etiologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   toxicita   MeSH
• nádory prsu farmakoterapie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• abstrakt z konference MeSH

Catecholamines are stress hormones and sympathetic neurotransmitters essential for control of cardiac function and metabolism. However, pathologically increased catecholamine levels may be cardiotoxic by mechanism that includes iron-catalyzed formation of reactive oxygen species. In this study, five iron chelators used in clinical practice were examined for their potential to protect cardiomyoblast-derived cell line H9c2 from the oxidative stress and toxicity induced by catecholamines epinephrine and isoprenaline and their oxidation products. Hydroxamate iron chelator desferrioxamine (DFO) significantly reduced oxidation of catecholamines to more toxic products and abolished redox activity of the catecholamine-iron complex at pH 7.4. However, due to its hydrophilicity and large molecule, DFO was able to protects cells only at very high and clinically unachievable concentrations. Two newer chelators, deferiprone (L1) and deferasirox (ICL670A), showed much better protective potential and were effective at one or two orders of magnitude lower concentrations as compared to DFO that were within their clinically relevant plasma levels. Ethylenediaminetetraacetic acid (EDTA), dexrazoxane (ICRF-187, clinically approved cardioprotective agent against anthracycline-induced cardiotoxicity) as well as selected beta adrenoreceptor antagonists and calcium channel blockers exerted no effect. Hence, results of the present study indicate that small, lipophilic and iron-specific chelators L1 and ICL670A can provide significant protection against the oxidative stress and cardiomyocyte damage exerted by catecholamines and/or their reactive oxidation intermediates. This potential new application of the clinically approved drugs L1 and ICL670A warrants further investigation, preferably using more complex in vivo animal models.

• MeSH
• buněčné linie MeSH
• chelátory železa farmakologie   MeSH
• kardiomyocyty účinky léků   metabolismus   MeSH
• kardiotonika farmakologie   MeSH
• kardiotoxiny antagonisté a inhibitory   toxicita   MeSH
• katecholaminy antagonisté a inhibitory   toxicita   MeSH
• krysa rodu rattus MeSH
• oxidace-redukce účinky léků   MeSH
• oxidační stres účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: Dexrazoxane (DEX, ICRF-187) is the only clinically approved cardioprotectant against anthracycline cardiotoxicity. It has been traditionally postulated to undergo hydrolysis to iron-chelating agent ADR-925 and to prevent anthracycline-induced oxidative stress, progressive cardiomyocyte degeneration and subsequent non-programmed cell death. However, the additional capability of DEX to protect cardiomyocytes from apoptosis has remained unsubstantiated under clinically relevant in vivo conditions. METHODS: Chronic anthracycline cardiotoxicity was induced in rabbits by repeated daunorubicin (DAU) administrations (3 mg kg(-1) weekly for 10 weeks). Cardiomyocyte apoptosis was evaluated using TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling) assay and activities of caspases 3/7, 8, 9 and 12. Lipoperoxidation was assayed using HPLC determination of myocardial malondialdehyde and 4-hydroxynonenal immunodetection. RESULTS: Dexrazoxane (60 mg kg(-1)) co-treatment was capable of overcoming DAU-induced mortality, left ventricular dysfunction, profound structural damage of the myocardium and release of cardiac troponin T and I to circulation. Moreover, for the first time, it has been shown that DEX affords significant and nearly complete cardioprotection against anthracycline-induced apoptosis in vivo and effectively suppresses the complex apoptotic signalling triggered by DAU. In individual animals, the severity of apoptotic parameters significantly correlated with cardiac function. However, this effective cardioprotection occurred without a significant decrease in anthracycline-induced lipoperoxidation. CONCLUSION: This study identifies inhibition of apoptosis as an important target for effective cardioprotection against chronic anthracycline cardiotoxicity and suggests that lipoperoxidation-independent mechanisms are involved in the cardioprotective action of DEX.

• MeSH
• antracykliny antagonisté a inhibitory   toxicita   MeSH
• apoptóza účinky léků   MeSH
• financování organizované MeSH
• kardiomyocyty cytologie   účinky léků   MeSH
• kardiotonika farmakologie   MeSH
• kardiotoxiny antagonisté a inhibitory   toxicita   MeSH
• králíci MeSH
• nemoci srdce chemicky indukované   patologie   prevence a kontrola   MeSH
• razoxan farmakologie   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• cytostatické látky aplikace a dávkování   škodlivé účinky   toxicita   MeSH
• ischemická choroba srdeční diagnóza   komplikace   MeSH
• kardiotoxiny klasifikace   škodlivé účinky   toxicita   MeSH
• lékařská onkologie metody   normy   MeSH
• lidé MeSH
• mezinárodní klasifikace nemocí normy   využití   MeSH
• National Cancer Institute (U.S.) normy   využití   MeSH
• nežádoucí účinky léčiv diagnóza   komplikace   MeSH
• perikarditida diagnóza   komplikace   MeSH
• srdeční arytmie diagnóza   komplikace   MeSH
• srdeční selhání diagnóza   komplikace   MeSH
• statistika jako téma MeSH
• Světová zdravotnická organizace MeSH
• Check Tag
• lidé MeSH

• MeSH
• experimenty na zvířatech MeSH
• financování organizované MeSH
• flavonoidy aplikace a dávkování   farmakologie   MeSH
• isoprenalin diagnostické užití   toxicita   MeSH
• kardiotoxiny diagnostické užití   toxicita   MeSH
• kardiovaskulární nemoci etiologie   farmakoterapie   MeSH
• katecholaminy diagnostické užití   toxicita   MeSH
• potkani Wistar MeSH
• reaktivní formy kyslíku farmakologie   MeSH
• rutin diagnostické užití   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• abstrakty MeSH

• MeSH
• antitumorózní látky * terapeutické užití   toxicita   MeSH
• antracykliny * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• dysfunkce levé srdeční komory diagnóza   komplikace   MeSH
• echokardiografie metody   využití   MeSH
• elektrokardiografie metody   využití   MeSH
• hematologické nádory farmakoterapie   komplikace   MeSH
• hodnotící studie jako téma MeSH
• kardiotoxiny * škodlivé účinky   toxicita   MeSH
• lékařská onkologie trendy   MeSH
• leukemie farmakoterapie   komplikace   MeSH
• lidé MeSH
• srdeční arytmie diagnóza   komplikace   MeSH
• statistika jako téma MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• Check Tag
• lidé MeSH