Why does doxorubicin affect the heart?
Doxorubicin appears to induce toxic damage to the mitochondria of cardiomyocytes. Several mitochondrial enzymes such as NADH dehydrogenase, cytochrome P-450 reductase and xanthine oxidase are involved in generating oxygen free radicals (reactive oxygen species) [3,23,24,25].
What is doxorubicin cardiomyopathy?
Doxorubicin (Dox) is a highly effective anticancer drug but cause acute ventricular dysfunction, and also induce late-onset cardiomyopathy and heart failure. Despite extensive studies, the pathogenic sequelae leading to the progression of Dox-associated cardiomyopathy remains unknown.
What is the primary toxicity of doxorubicin?
3. Multi-organ toxicity induced by Dox
| S·No. | Cell line/model | Dox dose |
|---|---|---|
| 11. | Ovarian cancer patients | – |
| Nervous system | ||
| 12. | Male Sprague-Dawley rats | 15 mg/kg as six injections for 2 weeks |
| 13. | Neuroblastic PC12 cells | 0–200 μM |
What chemo drug causes cardiotoxicity?
Cytostatic antibiotics of the anthracycline class are the best known of the chemotherapeutic agents that cause cardiotoxicity. Alkylating agents such as cyclophosphamide, ifosfamide, cisplatin, carmustine, busulfan, chlormethine and mitomycin have also been associated with cardiotoxicity.
How do you reduce cardiotoxicity of doxorubicin?
Use of PEGylated liposomal doxorubicin has been shown to decrease the cardiotoxicity of this anthracycline, even at doses >500 mg/m2 [64, 65]. The antioxidant, probucol, has been shown to prevent the decrease in LVEF in animal models of doxorubicin cardiotoxicity [66, 67].
What is the most common adverse reaction of doxorubicin?
Commonly reported side effects of doxorubicin include: severe nausea and vomiting, nausea and vomiting, and alopecia.
Why is doxorubicin fatal to a cell?
By binding to DNA and blocking mRNA synthesis, adriamycin effectively inhibits protein synthesis. Cessation of this process prevents the cell from replacing enzymes and other proteins required for cellular survival.
Is doxorubicin toxic to the heart?
It is well recognized that doxorubicin may cause damage to the heart in some individuals. While other anthracyclines (like epirubicin and mitoxantrone) may also cause heart damage, the chances are more common with doxorubicin. Doxorubicin causes both early and late heart damage (also called cardiotoxicity).
What is the most common chemotherapy drug to cause significant cardiotoxicity?
The most common chemotherapy drugs related to cardio-toxicity include: 5-fluorouracil (Adrucil) Paclitaxel (Taxol) Anthracyclines (a class of drugs)
Is doxorubicin cardiotoxicity reversible?
Because severe doxorubicin cardiotoxicity is reversible in some patients, aggressive supportive therapy is warranted.