Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits

Abstract

<jats:p> This study compares the chronic toxicity of two anthracyclines–daunorubicin and doxorubicin, commonly used for induction of anthracycline cardiomyopathy in the rabbit model. Such a comparative study has not been published until now. Both drugs were administered intravenously to male Chinchilla rabbits in doses at 3 mg/ kg (50 mg/m<jats:sup>2</jats:sup>) once weekly for 10 weeks. Selected biochemical, haematological and cardiovascular parameters and body weights were regularly monitored; additionally, a histological evaluation of heart, kidney and liver was performed at the end of the experiment. In the daunorubicin group, there were marked signs of the progressive development of heart failure, like the significant increases of the pre-ejection period/left ventricular ejection time index values (up to 134%)–and histological changes within the myocardium were also observed. On the other hand, the 10-week doxorubicin administration did not cause these changes that are typical for heart injury. Haematotoxicity, manifested particularly by aplastic anaemia, was apparent in both the experimental groups. Significant body weight loss (by 45.2%) and high premature mortality (100% versus 36.4%) reflected a greater general toxicity, especially nephrotoxicity of doxorubicin in comparison with daunorubicin. Further studies are necessary to find a possible explanation for these findings. </jats:p>

Cardioprotective Effect of Grape Seed Extract on Chronic Doxorubicin-Induced Cardiac Toxicity in Wistar Rats

“…25 In the present study, GSE treatment was also able to prevent the development of ECG changes induced by DOX and to confirm that GSE has a cardioprotective effect against DOX-induced cardiac dysfunction. In this study typical histopathological alterations such as noticeable interstitial edema, focal myocardial fibrosis, perinuclear vacuolation and myocardial necrosis was observed following DOX treatment as reported in different experimental animal models, 21,[47][48][49] including noticeable interstitial edema, focal myocardial fibrosis, perinuclear vacuolation and myocardial necrosis. Treatment with GSE decreased the infiltration of inflammatory cells including lymphocytes and macrophages into the myocardium of rats significantly, in comparison to DOX group ( Figure 7).…”

Cytoprotectivity of the natural honey against the toxic effects of Doxorubicin in mice

“…There has been a significant difference in demorphism and activities of mice treated with DOX and between those treated with DOX + honey. This difference might refer to the potency of honey to protect or to minimize the deteriorating effects of DOX via reducing free H 2 O 2 radicals [8,9] minimizing lipophosphate (LPO) which destroys the plasma membranes leading to many pathological and cellular changes [12][13][14][15][16]. Daily ingestion of honey therefore could protect body from many toxic effects of DOX or other chemicals.…”

“…These free radicals are believed to have a destructive role via provoking cells to produce H 2 O 2 radicals which react with lipids forming lipid peroxides (LPO) which destroy the plasma membranes leading to many pathological and cellular changes in a few body parts, e.g. heart [12], kidneys [13], liver [14,15] and genital organs [16].…”

Therapeutic effect of α-fetoprotein promoter-mediated tBid and chemotherapeutic agents on orthotopic liver tumor in mice

“…It is known that Dox can result in heavy body weight loss. 40,41 Further experiments using lower dose of Dox are needed to explore the possibility of its combination with Ad/ AFPtBid for treatment of HCC.…”