Pegylated and liposomal doxorubicin is associated with high mortality and causes limited cardiotoxicity in mice

BMC Research Notes
Christoffer StarkJuha Koskenvuo

Abstract

We wanted to determine the impact of different doses of a pegylated and liposomal formulation of the cardiotoxic drug doxorubicin on cardiac function, fibrosis and survival in mice. The drug causes myocardial damage by producing reactive oxygen species, mitochondrial damage and lipid peroxidation. Thymosin beta 4 is a peptide with cardioprotective, anti-oxidant and anti-fibrotic properties and we further investigated whether the peptide could attenuate this drug-induced injury by measuring cardiac function and fibrosis. Mice receiving high doses of doxorubicin died early during follow-up. Lowering the dose improved survival but did not markedly impair cardiac function on echocardiography and caused only limited fibrosis on histology. Thymosin beta 4 had only a mild protective effect on early cardiac function and did not significantly influence myocardial fibrosis. In conclusion, the use of pegylated and liposomal doxorubicin was not appropriate for inducing experimental cardiomyopathy. Thymosin beta 4 therapy was not beneficial in this setting.

References

Oct 26, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Xiaoming YiRalph V Shohet
May 27, 2008·Clinical Lymphoma & Myeloma·Rebecca Soloman, Alberto A Gabizon
Jul 11, 2008·Pediatric Research·Wuqiang ZhuLoren J Field
Oct 18, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jinzhou ZhuWei Han
Nov 15, 2011·Expert Opinion on Biological Therapy·Allan L GoldsteinHynda K Kleinman
Oct 11, 2012·Annals of the New York Academy of Sciences·Sudhiranjan GuptaIl-Kwon Kim
Apr 22, 2014·Current Treatment Options in Cardiovascular Medicine·Shashi RajSteven E Lipshultz
Jan 19, 2016·Toxicology and Applied Pharmacology·Michela PecoraroAda Popolo

❮ Previous
Next ❯

Citations

May 15, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Silvia BrunatoPaolo Caliceti
Aug 21, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Lulu AnTao Yan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiotoxicity

Cardiotoxicity refers to the muscle damage or dysfunction of heart electrophysiology caused by drug intake or due to disease complications. It is a well-known side effect of several cytotoxic drugs, especially of the anthracyclines and can lead to long term morbidity. Here is the latest research.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.