Hervé A. Gambliel

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Cardiac effects of anthracyclines or their metabolites may include both the stimulation and inhibition of Ca(2+) release from sarcoplasmic reticulum. In this study, the ability of daunorubicin and its primary metabolite, daunorubicinol, to stimulate and inhibit Ca(2+) release from canine sarcoplasmic reticulum (SR) vesicles was investigated. It was observed(More)
Utilizing a model of chronic doxorubicin cardiomyopathy, this study examines the relationship between changes in expression and function of calcium handling proteins and contractile dysfunction. A possible mechanism to account for this relationship is suggested. New Zealand white rabbits were injected with either doxorubicin (1 mg/kg, twice weekly for 8 wk)(More)
Chronic anthracycline administration to rabbits causes impairment of cardiac contractility and decreased gene expression of the calcium-induced calcium release channel of sarcoplasmic reticulum (SR), the ryanodine receptor (RYR2). The C-13 hydroxy metabolite (doxorubicinol), formed in the heart, has been hypothesized to contribute to anthracycline(More)
Plasmalemmal caveolae are a membrane specialization that mediates transcytosis across endothelial cells and the uptake of small molecules and ions by both epithelial and connective tissue cells. Recent findings suggest that caveolae may, in addition, be involved in signal transduction. To better understand the molecular composition of this membrane(More)
Anthracyclines can cause cumulative dose-related cardiotoxicity characterized by changes in Ca(2+) metabolism, including dysfunction of the sacroplasmic reticulum (SR) and decreased expression of Ca(2+)-handling proteins, such as the ryanodine receptor (RyR2). In this study, we examined the effect of dexrazoxane (ICRF-187), an iron chelator which prevents(More)
Anthracyclines are useful chemotherapeutic agents whose utility is limited by the development of irreversible cardiotoxicity. When tested, the pediatric population demonstrates an increased sensitivity to the cardiotoxicity of this class of agents, although the reasons for this increased sensitivity are unclear. The sarcoplasmic reticulum (SR) is a target(More)
Abstract Purpose. Although dexrazoxane (ICRF-187) is used clinically to protect against doxorubicin cardiotoxicity, the age-related effect of dexrazoxane on doxorubicin pharmacokinetics has not been well studied. Methods. We therefore examined the effect of pretreatment with dexrazoxane (50 mg kg–1 i.p. 1 h prior to administration of doxorubicin 2 mg kg–1(More)
Carbonyl reductase (CR) catalyzes the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of several carbonyls. Anthracyclines used to treat cancer are reduced by CR at the C13 carbonyl and the resulting metabolites are implicated in the cardiotoxicity associated with anthracycline therapy. CR also is believed to have a role in(More)
Because the risk of chronic anthracycline cardiotoxicity increases with age, the effect of chronic daunorubicin was compared in young (6–9 mo) and senescent (24–26 mo) Fischer 344 rats in cumulative doses of 12 or 18 mg/kg. Senescent rats treated using 18 mg/kg of daunorubicin did not survive because of daunorubicin toxicity. Rats were euthanized 1 wk after(More)
Chronic anthracycline administration results in a time- and dose-dependent cardiomyopathy. The Ca-ATPase of the sarcoplasmic reticulum, SERCA2, has been implicated as a principal target for anthracycline-induced cardiotoxicity. This hypothesis predicts that improved SERCA2 function would provide protection from cardiotoxic effects of anthracycline(More)