Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects

Despite the progress in the development of new anticancer strategies, cancer is rapidly spreading around the world and remains one of the most common diseases. For more than 40 years, doxorubicin has been widely used in the treatment of solid and hematological tumors. At the same time, the problem of its cardiotoxicity remains unresolved, despite the high efficiency of this drug. Symptomatic therapy is used as a treatment for side-effects of doxorubicin or pathological conditions that have already appeared in their background. To date, there are no treatment methods for doxorubicin cardiomyopathy as such. A drug such as nicotinamide riboside can play an important role in solving this problem. Nicotinamide riboside is a pyridine nucleoside similar to vitamin B3 that acts as a precursor to NAD+. There is no published research on nicotinamide riboside effects on cardiomyopathy, despite the abundance of works devoted to the mechanisms of its effects in various pathologies. The review analyzes information about the effects of nicotinamide riboside on various experimental models of pathologies, its role in the synthesis of NAD+, and also considers the possibility and prospects of its use for the prevention of doxorubicin cardiomyopathy.

Nicotinamide Riboside for the Prevention and Treatment of Doxorubicin Cardiomyopathy. Opportunities and Prospects.

Despite the progress in the development of new anticancer strategies, cancer is rapidly spreading around the world and remains one of the most common diseases. At the same time, oncological diseases are detected in patients with late stages of the course in the overwhelming majority of cases. This fact necessitates chemotherapy both as part of a combination and in the view of an independent form of treatment. For more than 40 years, doxorubicin has been widely used in the treatment of solid and hematological tumors. At the same time, the problem of its cardiotoxicity remains unresolved, despite the high efficiency of this drug. Symptomatic therapy is used as a treatment for side-effects of doxorubicin or pathological conditions that have already appeared on their background. To date, there are no treatment methods for doxorubicin cardiomyopathy as such. A drug such as nicotinamide riboside can play an important role in solving this problem. Nicotinamide riboside is a pyridine nucleoside similar to vitamin B3 that acts as a precursor to NAD+. There are no such works in cardiomyopathy, despite the abundance of works devoted to the mechanisms of realization of the effects of nicotinamide riboside in various pathologies. The review analyzes information about the effects of NR on various experimental models of pathologies, its role in the synthesis of NAD+, and also considers the possibility and prospects of its use for the prevention of doxorubicin cardiomyopathy.

Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician

Today the pharmacological possibilities of treating cancer are expanding and as a result, life expectancy is increasing against the background of chemotherapy and supportive treatment. In the conditions of successful antitumor treatment, complications associated with its toxic effect on healthy tissues and organs began to come to the fore. Anthracycline cardiomyopathy was the first serious cardiovascular complication to draw the attention of oncologists and cardiologists around the world. Anthracycline drugs such as doxorubicin, epirubicin, idarubicin are still widely used in oncological practice to treat a wide range of solid and hematological malignancies. Doxorubicin-induced cardiomyopathy is closely associated with an increase in oxidative stress, as evidenced by reactive oxygen species (ROS) nduced damage such as lipid peroxidation, and decreased levels of antioxidants. Myofibrillar destruction and dysregulation of intracellular calcium are also important mechanisms, usually associated with doxorubicin-induced cardiotoxicity. Despite the abundance of data on various mechanisms involved in the implementation of doxorubicin-induced cardiotoxicity, a final understanding of the mechanism of the development of doxorubicin cardiomyopathy has not yet been formed. It poses the most significant challenges to the development of new methods of prevention and treatment, as well as to the unambiguous choice of a specific treatment regimen using the existing pharmacological tools. In order to resolve these issues new models that could reflect the development of the chemotherapy drugs effects are needed. In this review we have summarized and analyzed information on the main existing models of doxorubicin cardiomyopathy using small laboratory animals. In addition, this paper discusses further areas of research devoted to the development and validation of new improved models of doxorubicin cardiomyopathy suitable both for studying the mechanisms of its implementation and for the preclinical drugs effectiveness assessment.

Acute Ischemic Stroke in a Young Patient with Left Ventricular Thrombus Attributed to Doxorubicin Cardiomyopathy

We report a case of acute middle cerebral territory ischemic infarction caused by left ventricular thrombus (LVT) in a doxorubicin cardiomyopathy patient. A major adverse effect of doxorubicin is cardiotoxicity. In doxorubicin cardiomyopathy, as the ventricular contractility decreases, LVT can occur and lead to systemic embolic events such as stroke.

Evaluation of the effectiveness of pharmacotherapy for brain and heart diseases by monitoring the effects of drugs

Introduction: The study aims at analyzing the possibility of using a method of monitoring the action of drugs in real-time to assess the effectiveness of pharmacotherapy for brain and heart lesions. Materials and methods: To assess the effect of drugs in the experiment and in the clinic, the temperature difference between the biologically active point and the intact skin zone was recorded every second for 2 minutes. The work involved experimental and clinical parts. The experimental study was performed on 81 rabbits. In the experiment, the effect of Meldonium was evaluated when treating doxorubicin cardiomyopathy and the effect of Cortexin – when treating experimental brain ischemia. The clinical testing of the method involved 10 healthy volunteers and 20 patients of both sexes, diagnosed with acute cerebrovascular events of the ischemic-stroke type. Results and discussions: An increase of some indicators of differential thermometry of the biologically active point by 60% or more on the 7th day of the treatment concerning the values obtained before the treatment is indicative of a high probability of pronounced positive dynamics in the treatment of doxorubicin cardiomyopathy. If on the 7th day of the treatment, some indicators of differential thermometry of biologically active point С7 to exceed by 20% or more the similar indicators before the treatment, a high probability of pronounced positive dynamics in the treatment of ischemic stroke can be inferred. Conclusion: A safe, non-invasive method for monitoring the effects of drugs in real-time, which does not require any special training of a doctor, has been developed.

Cardioprotective Effectiveness of a Combination of 2-Ethyl-6-Methyl-3-Hydroxypyridine Enantiomers and Rosuvastatin in a Model of Doxorubicin Cardiomyopathy

Aim. To study the cardioprotective effect of levorotatory ethylmethylhydroxypyridine malate enantiomer in combination with rosuvastatin on the model of doxorubicin cardiomyopathy.Material and methods. The research was conducted using 80 Langendorff perfused Wistar rat hearts (OOO “Kardioprotekt”, Saint-Petersburg) after a 3-day simulation of doxorubicin cardiomyopathy. The selection criteria for the evaluation of cardioprotective effect in the administration of ethylmethylhydroxypyridine derivatives and their combination with rosuvastatin were the indicators of left ventricular contractility, Tension-Time Index (t TTI), the diameter of cardiomyocytes.Results. During the experiment, it was found that the introduction of doxorubicin has a cardiotoxic effect, manifested through a decrease in the left ventricle contractility by 30–45% and an increase in the t TTI index by 4 times (“diastolic defect”). The introduction of a racemic mixture of ethylmethylhydroxypyridine malate at a dose of 93 mg/kg prevents the reduction of the left ventricle contractility and prevents the development of a “diastolic defect”, restraining the increase in the t TTI index by 32%, while the ethylmethylhydroxypyridine enantiomer at a dose of 93 mg/kg is more effective and its positive effect increases in combination with rosuvastatin at a dose of 0.4 mg/kg.Conclusion. The use of oxypyridine derivatives at doses of 50 mg/kg and 93 mg/kg, as well as their combination with rosuvastatin prevented the development of a “diastolic defect”. The highest effi ciency was revealed for the use of a combination of levorotatory ethylmethylhydroxypyridine malate enantiomer at a dose of 93 mg/kg with rosuvastatin at a dose of 0.4 mg/kg.