DOX and induced cardiotoxicity

Abstract

Cancer, one of the most important and deadly diseases of our age, is very difficult to treat. The toxic effects of the drugs used affect the antineoplastic treatment. Anthracyclines are substances that have been proven to be beneficial in cancer chemotherapy in research on microbial products. Doxorubicin is one of the chemotherapeutic agents used in cancer treatment. A broad-spectrum anthracycline is known to have beneficial effects such as antibiotics, as well as adverse effects such as cardiac damage. Doxorubicin causes reactive oxygen radicals in the cell. Today, new natural antioxidant sources are of great importance because of the importance of using antioxidant molecules in the treatment of diseases caused by free radicals. Therefore, it has been shown that the use of antioxidants may be protective against oxidative stress caused by doxorubicin and other cytotoxic drugs. Due to the antioxidant properties of Pistacia vera L. (P. v. L.), which has a high phenolic content, it has been shown in various studies that it is beneficial in anti-inflammatory activity, glycemic control and protection of endothelial function and prevents low oxidation.

Keywords

Discussion

With the increasing incidence of cancer in recent years, increased doses of antineoplastic drugs and more diverse combinations have been used to provide better toxicity control in these patients.²⁷ DOX is a chemotherapeutic agent of the anthracycline group used for the destruction of tumors. DOX has the ability to inhibit DNA biosynthesis by DNA intercalation. This drug has high affinity for sites containing Guanine-Cytosine (GC) base pairs and forming hydrogen bonds between DOX and guanine, causing the formation of triple DOX-DNAtopoisomerase II complexes that activate DNA damage responses and eventually cause cell death.²⁸ Demir et al. evaluated the antioxidant system and lipid peroxidation after the last DOX injection in cardiotoxicity studies induced by DOX, and showed that DOX reduces heart tissue GSH-Px and increases lipid peroxidation products in the chronic process.²⁹ In recent years, biological markers have been used together with ECHO to detect cardiotoxicity due to anthracyclines. ProBNP and troponin I are two of these markers.³⁰ Troponin (Troponin-I, Troponin-C), CK-MB and brain natriuretic peptide (BNP) markers are the most important markers used to define cardiac damage and to describe the failure that occurs after this damage. DOX has long been thought to act as a pro-oxidative agent, but a large number of studies, demonstrated that this anticancer drug can induce significant oxidative stress within cells.³¹ Free radicals, which are the products of oxidation reactions, cause damage to cells and tissues; Eventually, it causes many chronic diseases such as cardiovascular and cancer.³² Oxidative damage to membrane lipids and other cellular components is thought to be the major factor in the toxicity of DOX and other anthracyclic antibiotics. For this reason, it has been proven in most studies that the use of natural and artificial antioxidants protects against oxidative stress caused by DOX and other drugs in this derivative.³³ While the use of antioxidants has been shown to play a positive role in the treatment of the most common diseases such as CVD and cancer, studies among healthy people and people with heart disease have shown that antioxidants reduce free radicals and protect LDL against oxidation.³⁴ Dong et al.³⁵ reported that quercetin, a powerful antioxidant, suppressed DOX-induced cardiotoxicity. Carino-Cortes et al.³⁶ reported that naringin, with Daunorubicin, an anticancer agent, prevents DNA damage that starts as a result of oxidative stress in hepatocytes and cardiocytes.In recent years, P.v.L., rich in phenolic compounds, which is a very powerful antioxidant, has been shown to have protective effects against diseases associated with increased oxidative stress as a result of excessive production of free radicals such as cardiovascular diseases (CVD) and cancer.³⁷ Studies have shown that consumption of green pistachios (P.v.L.) significantly reduces total cholesterol.³⁸ and LDL.³⁹ while significantly increasing low-density lipoprotein. In a study on this subject, it was determined that the outer shell of the peanut contains high antioxidants.⁴⁰

Conclusion

As a result of this research, besides the advantages provided by the therapeutic properties of DOX, the cardiotoxicity caused by its use causes the production of free oxygen radicals. To reduce these effects, the use of natural or artificial antibiotics is needed. Therefore, the discovery of new antibiotics is of great importance.

Declarations

Abbreviations

BNP: Brain natriuretic peptide
CK-MB: Creatine kinase myocardial band
CVD: Cardiovascular disease
DNA: Deoxyribonucleic acid
DOX: Doxorubicin
GC: Guanine-cytosine
GSH-Px: Glutathione peroxidase
LDL: Low-density lipoprotein
P. v. L.: Pistacia vera L.
RNA: Ribonucleic acid
SOR: Superoxide oxygen radicals

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Figures

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Figure 1. Chemical structure of DOX.¹

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