Can short-term fasting protect against doxorubicin-induced cardiotoxicity?

Abstract

a potential strategy to prevent Dox-induced cardiotoxicity. Future research should aim to determine the optimal regimen of fasting, confirmation that this regimen does not interfere with the antitumor properties of Dox, as well as the underlying mechanisms exerting the cardioprotective effects.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Fasting; Doxorubicin; Cardiotoxicity; Cardioprotection Core tip: Doxorubicin (Dox)-induced cardiotoxicity remains a significant cause of morbidity and mortality in cancer survivors, despite the intensive investigation of potential protective strategies. Studies have shown that shortterm fasting induces cardioprotective effects against Doxinduced injury. Importantly, evidence suggests that fasting may enhance the antitumor effects of Dox. Thus, shortterm fasting may be a feasible practice that can easily be incorporated into the treatment plans of cancer patients. Abstract Doxorubicin (Dox) is one of the most effective chemotherapeutic agents used in the treatment of several types of cancer. However the use is limited by cardiotoxicity. Despite extensive investigation into the mechanisms of toxicity and preventative strategies, Dox-induced cardiotoxicity still remains a major cause of morbidity and mortality in cancer survivors. Thus, continued research into preventative strategies is vital. Short-term fasting has proven to be cardioprotective against a variety of insults. Despite the potential, only a few studies have been conducted investigating its ability to prevent Dox-induced cardiotoxicity. However, all show proof-of-principle that short-term fasting is cardioprotective against Dox. Fasting affects a plethora of cellular processes making it difficult to discern the mechanism(s) translating fasting to cardioprotection, but may involve suppression of insulin and insulin-like growth factor-1 signaling with stimulated autophagy. It is likely that additional mechanisms also contribute. Importantly, the literature suggests that fasting may enhance the antitumor activity of Dox. Thus, fasting is a regimen that warrants further investigation as

Effects of Dietary Restriction on Cancer Development and Progression

“…The usefulness of STS has also been demonstrated for its attenuating properties on chemotherapy side effects. Indeed, its cardioprotective properties have been recently demonstrated during doxorubicin-based treatments (Dirks-Naylor et al 2014). In addition, a recent work on murine models revealed that following a prolonged fasting of 48-60 h prior to the administration of a high dose of etoposide, the side effects, generally resulting from the treatment, were attenuated (Raffaghello et al 2008).…”

Doxorubicin-Induced Cardiotoxicity

“…Although calorie restriction mimetics are more practical in terms of sustainability, they are less accessible and cost ineffective. Fasting has been shown to exert beneficial effects on certain forms of cardiovascular diseases including age-related cardiac hypertrophy, myocardial ischemic injury, and coronary heart disease risk factors through diverse mechanisms including remodeling of mitochondrial networks, improvement of energy metabolism, reduction in signaling pathways related to survival such as insulin and insulin-like growth factor-1 signaling, decrease in mitochondrial oxidative stress, and enhancement of autophagic flux [97,98]. Recent studies suggest that fasting also conferred cardioprotection against DOX cardiotoxicity.…”

“…Recent studies suggest that fasting also conferred cardioprotection against DOX cardiotoxicity. In animal models, short-term fasting ameliorates cardiac damage and cardiac dysfunction caused by DOX [98]. Alternate-day fasting, a type of intermittent fasting, is capable of mitigating DOX cardiotoxicity in mouse models of both acute and chronic DOX cardiotoxicity [30].…”

Dietary restriction: could it be considered as speed bump on tumor progression road?

“…Some studies have shown that STS induces cardioprotective effects against the injury caused by doxorubicin [56]. Moreover, Raffaghello et al [54] studied the effects of high-dose etoposide, a chemotherapeutic drug with a non-specific toxicity profile, in murine models undergone to fasting for 48-60 h, before the administration of a high-dose drug, and in a control group fed ad libitum.…”