Flavonoids as protectors against doxorubicin cardiotoxicity: Role of iron chelation, antioxidant activity and inhibition of carbonyl reductase.

AB - Anthracycline antibiotics (e.g. doxorubicin and daunorubicin) are among the most effective and widely used anticancer drugs. Unfortunately, their clinical use is limited by the dose-dependent cardiotoxicity. Flavonoids represent a potentially attractive class of compounds to mitigate the anthracycline cardiotoxicity due to their iron-chelating, ant

New iron chelators in anthracycline-induced cardiotoxicity.

The use of anthracycline anticancer drugs is limited by a cumulative, dose-dependent cardiac toxicity. Iron chelation has long been considered as a promising strategy to limit this unfavorable side effect, either by restoring the disturbed cellular iron homeostasis or by removing redox-active iron, which may promote anthracycline-induced oxidative stress. Aroylhydrazone lipophilic iron chelators have shown promising results in the rabbit model of daunorubicin-induced cardiomyopathy as well as in cellular models. The lack of interference with the antiproliferative effects of the anthracyclines also favors their use in clinical settings. The dose, however, should be carefully titrated to prevent iron depletion, which apparently also applies for other strong iron chelators. We have shown that a mere ability of a compound to chelate iron is not the sole determinant of a good cardioprotector and the protective potential does not directly correlate with the ability of the chelators to prevent hydroxyl radical formation. These findings, however, do not weaken the role of iron in doxorubicin cardiotoxicity as such, they rather appeal for further investigations into the molecular mechanisms how anthracyclines interact with iron and how iron chelation may interfere with these processes

Usnic acid: potential role in management of wound infections

Usnic acid (UA) is a secondary lichen metabolite extensively studied for the broad variety of biological features. The most interesting property of UA is its antimicrobial activity against Gram-positive bacteria growing either in planktonic or in biofilm mode. In this chapter, the most relevant studies assessing usnic acid activity against microbial biofilms have been summarized and the potential role of UA in the management of biofilm-based wound infections has been critically discussed. Additionally, an overview of the main strategies adopted so far to reduce drug toxicity and increase bioavailability is given in the perspective of a safe use of UA in the clinical management of infected wounds