Key result
Nicorandil (3 mg/kg) protected rat cardiac tissues against doxorubicin-induced cardiotoxicity by normalizing biochemical and oxidative stress parameters, an effect reversed by glibenclamide.
Why the study?
Does nicorandil prevent doxorubicin-induced cardiotoxicity in rats?
Does nicorandil prevent doxorubicin-induced cardiotoxicity in rats?
Nicorandil demonstrates cardioprotective effects against doxorubicin-induced cardiotoxicity in a rat model, likely mediated through mitochondrial KATP channel opening.
Animal data preclude nicorandil use for doxorubicin cardiotoxicity; leaves open KATP-mediated cardioprotection for human trials.
Doxorubicin is a chemotherapeutic drug used to treat solid and haematopoietic tumours. Its use is limited by a major side effect of cardiotoxicity. It was reported that doxorubicin-induced cardiotoxicity is mediated through oxidative stress coupled with impaired NO bioavailability and NF-κB activation. Nicorandil, a mitochondrial ATP-dependent potassium (KATP ) channel opener, was reported to be cardioprotective on ischaemic myocardium. However, the effect of nicorandil against doxorubicin-induced cardiotoxicity has not yet been clarified. Accordingly, six groups of rats were used. The first three groups were injected with vehicle, nicorandil (3 mg/kg) orally and doxorubicin (a single intraperitoneal injection of 20 mg/kg), respectively. Group four was treated with nicorandil, whereas group five was treated with glibenclamide and then nicorandil starting 2 days before doxorubicin and continued for five consecutive days. Group six was treated with glibenclamide alone. At the end of the experiment, the rats were killed. Cardiac enzyme indexes were measured in serum. Heart tissues were processed for determination of nitrite/nitrate, NF-κB protein expression, glutathione (GSH), lipid peroxide (TBARS) levels and superoxide production. In addition to body-weight reduction, doxorubicin produced cardiotoxicity as indicated from the increase in lactate dehydrogenase (LDH), creatine kinase (CK) activities, TBARS, superoxide production, NF-κB expression and caspase-3 activity. Moreover, doxorubicin decreased GSH and nitrite/nitrate levels. Histopathological examination of doxorubicin-treated hearts revealed degenerative changes. On the other hand, nicorandil protected cardiac tissues against doxorubicin cardiotoxicity as demonstrated from normalization of cardiac biochemical and oxidative stress parameters and amelioration of histopathological changes. Glibenclamide, a blocker of the KATP channel, reversed most of the cardiac effects of nicorandil.
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Abdel‐Raheem et al. (2013) studied Doxorubicin-induced cardiotoxicity. Nicorandil vs. Vehicle, doxorubicin alone, and glibenclamide was evaluated on Cardiac enzyme indexes, oxidative stress parameters, and histopathological changes. Nicorandil (3 mg/kg) protected rat cardiac tissues against doxorubicin-induced cardiotoxicity by normalizing biochemical and oxidative stress parameters, an effect reversed by glibenclamide.
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