rutin and Cardiomyopathies

We report the case of a 55-year-old woman with heart failure with preserved ejection fraction (HFpEF), who presented with hypertensive urgency and pulmonary oedema. The patient was medically optimized and underwent cardiac catheterization revealing pulmonary hypertension, elevated pulmonary capillary wedge pressure, normal cardiac index, and non-obstructive coronary disease. Invasive evaluation of coronary flow revealed blunted coronary flow reserve and increased index of microvascular resistance. Cardiac magnetic resonance imaging demonstrated reduced global myocardial perfusion and diffuse interstitial fibrosis. This case exhibits a potential HFpEF phenotype associated with microvascular dysfunction, fibrosis, and elevated filling pressures.

Topics: Cardiomyopathies; Coronary Angiography; Coronary Circulation; Coronary Vessels; Echocardiography; Electrocardiography; Female; Fibrosis; Heart Failure; Humans; Hydroxyethylrutoside; Microcirculation; Middle Aged; Myocardium; Pulmonary Wedge Pressure; Stroke Volume; Ventricular Function, Left

Cardiac damage is the major limiting factor for the clinical use of doxorubicin (DOX). Preclinical studies indicate that inflammatory effects may be involved in DOX-induced cardiotoxicity. Nepsilon-(carboxymethyl) lysine (CML) is suggested to be generated subsequent to oxidative stress, including inflammation. Therefore, the aim of this study was to investigate whether CML increased in the heart after DOX and whether anti-inflammatory agents reduced this effect in addition to their possible protection on DOX-induced cardiotoxicity. These effects were compared with those of the potential cardioprotector 7-monohydroxyethylrutoside (monoHER).BALB/c mice were treated with saline, DOX alone or DOX preceded by ketoprofen (KP), dexamethasone (DEX) or monoHER. Cardiac damage was evaluated according to Billingham. Nepsilon-(carboxymethyl) lysine was quantified immunohistochemically. Compared to saline, a 21.6-fold increase of damaged cardiomyocytes was observed in mice treated with DOX (P<0.001). Addition of KP, DEX or monoHER before DOX significantly reduced the mean ratio of abnormal cardiomyocytes in comparison to mice treated with DOX alone (P

Topics: Animals; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Cardiomyopathies; Dexamethasone; Doxorubicin; Glycation End Products, Advanced; Hydroxyethylrutoside; Immunohistochemistry; Ketoprofen; Lysine; Male; Mice; Mice, Inbred BALB C; Myocytes, Cardiac

Despite its well-known cardiotoxicity, the anthracyclin doxorubicin (DOX) continues to be an effective and widely used chemotherapeutic agent. DOX-induced cardiac damage presumably results from the formation of free radicals by DOX. Reactive oxygen species particularly affect the cardiac myocytes because these cells seem to have a relatively poor antioxidant defense system. The semisynthetic flavonoid monohydroxyethylrutoside (monoHER) showed cardioprotection against DOX-induced cardiotoxicity through its radical scavenging and iron chelating properties. Because of the relatively short final half-life of monoHER (about 30 min), it is expected that the time interval between monoHER and DOX might be of influence on the cardioprotective effect of monoHER. Therefore, the aim of the present study was to investigate this possible effect.. Six groups of 6 BALB/c mice were treated with saline, DOX alone or DOX (4 mg/kg i.v.) preceded by monoHER (500 mg/kg i.p.) with an interval of 10, 30, 60 or 120 min. After a 6-week treatment period and additional observation for 2 weeks, the mice were sacrificed. Their cardiac tissues were processed for light microscopy, after which cardiomyocyte damage was evaluated according to Billingham (in Cancer Treat Rep 62(6):865-872, 1978). Microscopic evaluation revealed that treatment with DOX alone induced significant cardiac damage in comparison to the saline control group (P<0.001).. The number of damaged cardiomyocytes was 9.6-fold (95% CI 4.4-21.0) higher in mice treated with DOX alone than that in animals of the control group. The ratio of aberrant cardiomyocytes in mice treated with DOX preceded by monoHER and those in mice treated with saline ranged from 1.6 to 2.8 (mean 2.2, 95% CI 1.2-4.1, P=0.019). The mean protective effect by adding monoHER before DOX led to a significant 4.4-fold reduction (P<0.001, 95% CI 2.3-8.2) of abnormal cardiomyocytes. This protective effect did not depend on the time interval between monoHER and DOX administration (P=0.345).. The results indicate that in an outpatient clinical setting monoHER may be administered shortly before DOX.

Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Dose-Response Relationship, Drug; Doxorubicin; Hydroxyethylrutoside; Injections, Intraperitoneal; Injections, Intravenous; Male; Mice; Mice, Inbred BALB C; Microscopy, Video; Myocytes, Cardiac; Time Factors; Toxicity Tests, Acute; Vacuoles

The cumulative dose-related cardiotoxicity of doxorubicin is believed to be caused by the production of oxygen- free radicals. 7-Monohydroxyethylrutoside (monoHER), a semisynthetic flavonoid and powerful antioxidant, was investigated with respect to the prevention of doxorubicin-induced cardiotoxicity in mice and to its influence on the antitumor activity of doxorubicin in vitro and in vivo. Non-tumor-bearing mice were equipped with a telemeter in the peritoneal cavity. They were given six weekly doses of 4 mg/kg doxorubicin i.v., alone or in combination with either 100 or 250 mg/kg monoHER i.p., 1 h prior to doxorubicin administration and for the following 4 days. Cardiotoxic effects were measured from electrocardiogram changes up to 2 weeks after treatment. Protection against cardiotoxicity was found to be dose dependent, with 53 and 75% protection, respectively, as calculated from the reduction in the increase in the ST interval. MonoHER and several other flavonoids with good antioxidant properties were tested for their antiproliferative effects in the absence or the presence of doxorubicin in A2780 and OVCAR-3 human ovarian cancer cells and MCF-7 human breast cancer cells in vitro. Some flavonoids were directly toxic at 50 and 100 microM, whereas others, including monoHER, did not influence the antiproliferative effects of doxorubicin at these concentrations. The influence of monoHER was further tested on the growth-inhibitory effect of 8 mg/kg doxorubicin i.v., given twice with an interval of 1 week in A2780 and OVCAR-3 cells that were grown as s.c. xenografts in nude mice. MonoHER, administered 1 h before doxorubicin in a dose schedule of 500 mg/kg i.p. 2 or 5 days per week, was not toxic and did not decrease the antitumor activity of doxorubicin. It can be concluded that monoHER showed a dose-dependent protection against chronic cardiotoxicity and did not influence the antitumor activity of doxorubicin in vitro or in vivo.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Breast Neoplasms; Cardiomyopathies; Catechin; Chelation Therapy; Cystadenocarcinoma, Serous; Dose-Response Relationship, Drug; Doxorubicin; Drug Interactions; Electrocardiography; Female; Flavonoids; Flavonols; Free Radical Scavengers; Free Radicals; Humans; Hydroxyethylrutoside; Iron; Iron Chelating Agents; Kaempferols; Mice; Mice, Nude; Molecular Structure; Neoplasm Transplantation; Ovarian Neoplasms; Quercetin; Razoxane; Rutin; Telemetry; Tumor Cells, Cultured; Weight Loss