Adriamycin-induced Cardiac Toxicity Research Articles

Cardioprotective Effect of High-Intensity Aerobic Interval Training against Adriamycin-Induced Cardiac Toxicity in Rats

Cardioprotective Effect of High-Intensity Aerobic Interval Training against Adriamycin-Induced Cardiac Toxicity in Rats

Protective effect of <i>Balanites aegyptiaca</i> on antioxidant defense system against adriamycin-induced cardiac toxicity in expermental mice

Adriamycin is an anthracycline antibiotic that is widely used as a chemotherapeutic agent. However, usefulness of this agent is limited due to its cardiotoxic effects. Increased oxidative stress and antioxidant deficit have been suggested to play a major role in adriamycin induced cardiomyopathy and congestive heart failure due to multiple treatments with adriamycin. The rationale of the present study was to evaluate the potential protective effect of Balanites aegyptiaca (B. aegyptiaca) as a source of the natural antioxidants against adriamycin-induced cardiotoxicity in experimental mice. In present study, four groups (ten animals in each group) of experimental mice were used as follows: Group 1, mice not received both Adriamycin drug and B. aegyptiaca extract and served as a negative control group; Group 2, mice received Adriamycin intraperitoneally (2.5 mg/kg BW) in six equal injections over a period of two weeks for a cumulative dose of 15 mg/kg BW; Group 3, mice orally administered with B. aegyptiaca extract (400 mg/kg BW), through an intragastric feeding tube over a period of three weeks; Group 4, mice treated orally with B. aegyptiaca extract plus intraperitoneally adriamycin administration (2.5 mg/kg BW). Serum Lactate dehydrogenase (LDH), Creatine phosphokinase (CPK), Glutamate oxaloacetate transaminase (GOT), Glutamate pyruvate transaminase (GPT), Lipid peroxide (LPO), total Nitric oxide (NO), erythrocyte lysate Superoxide dismutase (SOD), Glutathion peroxidase (GPx) and plasma Catalase (CAT) were measured in all tested groups. The results showed that, Adriamycin elevated the activities of LDH, CPK, GOT, GPT, LPO and total NO content in the mice heart tissue. Also, Adriamycin drug reduced the activities of SOD, GPx and CAT. Pretreatment with B. aegyptiaca extract significantly (p either reduced or completely prevented its toxic effects. So, these findings demonstrate the cardio protective effect of B. aegyptiaca on antioxidant tissue defense system during Adriamycin induced cardiac damage in mice. Therefore it could be recommended for further investigation in this potentially new indication for clinical application. Keywords: Adriamycin, Cardiotoxicity, natural antioxidant, antioxidant enzymes.

Effects of Adriamycin on Ionic Currents in Single Cardiac Myocytes of the Rabbit

Adriamycin has been widely used as an anticancer drug, but its clinical use is limited by a dose-dependent cardiac toxicity. Proposed mechanisms for the adriamycin-induced cardiomyopathy include increasing the Ca current, inhibiting the Na/Ca exchange and dysfunction of the sarcoplasmic reticulum (SR). Using the whole cell voltage clamp technique in single isolated atrial and ventricular myocytes of the rabbit, we have investigated the effect of adriamycin on various current systems which are related to regulating intracellular Ca concentration: the Ca current, the Na/Ca exchange current and [Ca2+]1-dependent currents (ouabain-induced transient inward current and the inward tail current). Adriamycin, 0.05 mg/ml, increased Ca current (L-type) by 61%. Adriamycin inhibited the inward tail current in a dose-dependent manner between 0.02 and 0.1 mg/ml and when low concentration was used the effect was reversible. Ouabain-induced transient inward current was also suppressed by 0.05 mg/ml adriamycin. Na/Ca exchange current which is partly responsible for inducing [Ca2+]1-dependent currents was, however, not affected by adriamycin, suggesting that the effect adriamycin on [Ca2+]1-dependent currents is due to inhibition of SR function. From these results it is suggested that the increase of Ca current and inhibition of SR function cause adriamycin-induced cardiac toxicity: SR dysfunction not only causes a decease of myocardial contractility, it can also accelerate the Ca overload process which might originate from the increase of Ca current.

A model of left ventricular dysfunction caused by intracoronary adriamycin

Experimental evaluation of new therapy for congestive heart failure has been hampered by the lack of a simple and reliable animal model of heart failure. This study was undertaken to develop a canine model of chronic left ventricular dysfunction. A left thoracotomy was performed in 9 adult mongrel dogs. A 1.5-mm Silastic (Dow Corning) catheter with an attached subcutaneous access port was positioned in the left main coronary artery. Six animals received five weekly infusions of Adriamycin (doxorubicin hydrochloride) (10 mg/wk), and 3 received saline solution. Hemodynamic studies were performed before insertion of the catheter and 2 weeks after completion of the infusions. In animals that received Adriamycin, rest ejection fraction declined from 0.54 ± 0.03 to 0.35 ± 0.03, cardiac output fell from 5.6 ± 0.6 to 3.9 ±0.5 L/min, and left ventricular end-diastolic volume increased from 76 ± 9 to 99 ± 12 mL ( p < 0.05). There was a small increase in right atrial pressure (2.7 ± 1 versus 5.7 ± 1 mm Hg) but no change in right ventricular ejection fraction (0.31 ± 0.04 versus 0.30 ± 0.03). In no animal did alopecia, weight loss, neutropenia, or anemia develop. Histological changes consistent with Adriamycin-induced cardiac toxicity were found in each dog. No significant hemodynamic or histological changes occurred in the control animals. Administration of Adriamycin into the left main coronary artery causes left ventricular dysfunction without resulting in systemic side effects or compromising right ventricular function. This animal model could be used to evaluate the effects of new possible therapy, such as cardiomyoplasty, on left ventricular failure.

Clinical and pharmacologic investigation of the effects of alpha-tocopherol on adriamycin cardiotoxicity.

Our data indicate that alpha-tocopherol used in an oral dose of 2 g/m2 daily results in a six- to eightfold increase of the vitamin E levels in serum. The occurrence of congestive heart failure in three patients and the observation of significant pathologic changes in endomyocardial biopsies in approximately half of the patients treated with a median cumulative adriamycin dose level of 550 mg/m2 indicate that alpha-tocopherol does not offer substantial protection against adriamycin-induced cardiac toxicity. The antitumor activity of the drug, however, is not compromised by the concomitant administration of the vitamin.

Radionuclide Demonstrations of Adriamycininduced Cardiac Toxicity

A case is presented in which adriamycin toxicity was clinically suspected and confirmed through the use of 99mTc-pyrophosphate myocardial scanning. Additionally, the course of regression of this process also appeared to be confirmed by serial myocardial scanning. A possible use of this diagnostic technique in the evaluation of patients receiving adriamycin chemotherapy is suggested.