Isosorbide dinitrate improves doxorubicin-induced cardiotoxicity via diminishing proinflammatory mediators, oxidative stress, and apoptosis

Main Article Content

Hussein J. Al-Amir
Ali M. Janabi
Salim F. Kadhim
Rafid M.A. Wasfi

Keywords

isosorbide dinitrate, doxorubicin-induced cardiotoxicity, inflammation, oxidative stress, and apoptosis

Abstract

Cardiotoxicity is the presence of cardiac dysfunction resulting from electrical or muscle injury, which results in heart toxicity. The heart weakens and becomes less efficient in pumping blood. Cardiotoxicity is one of chemotherapy most serious side effects, with significantly increased morbidity and mortality. Isosorbide dinitrate is an antianginal agent used to treat chest pain in people with a certain heart condition (coronary artery disease). This medication belongs to the nitrate drug class. It works by relaxing and widening blood vessels, allowing more blood to flow to the heart. The role of isosorbide dinitrate in doxorubicin-induced cardiotoxicity reduction or prevention is briefly discussed in this work. The 28 male rats were randomly split into four groups (7 rats in each group). The control group of rats was provided with natural food and drink. For two weeks, rats in the normal saline group were fed 0.9% normal saline. For those in the doxorubicin-induced group, 2.5 mg/kg was administered thrice weekly to the rats for two weeks. ISDN group (treated with ISDN): ISDN was administered orally (10 mg/kg/d) for two weeks. Heart damage was a result of doxorubicin treatment. Cardiac tissues of doxorubicin-treated rats showed elevated tumor necrosis factor-alpha, interleukin-1beta, malondialdehyde, and caspase-3 levels (p<0.05), while total antioxidant capacity and Bcl-2 levels were considerably decreased (P<0.05). Inflammatory markers (TNF-α and IL-1β) are reduced after ISDN treatment, providing strong evidence that ISDN considerably mitigates doxorubicin-induced cardiotoxicity (P<0.05). In addition, total antioxidant capacity was considerably increased in the ISDN group compared to the doxorubicin-only group (P<0.05), whereas the oxidative marker malondialdehyde in cardiac tissue was decreased (P<0.05). ISDN dramatically mitigated doxorubicin-induced cardiotoxicity in rats by modulating oxidative stress, the inflammatory response, and the apoptotic pathway. This research aimed to see if ISDN may prevent doxorubicin-induced cardiotoxicity by limiting the effects of the medication on inflammation pathways, oxidative pathways, and apoptotic pathways.

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