The possible protective effect of aldehyde dehydrogenase 2 agonist (Alda-1) on doxorubicin induced toxicity of the left ventricular cardiomyocytes of adult male mice.

Abstract

Background: Doxorubicin (DOX) is an effective antineoplastic drug. However, its cardiotoxicity is a major obstacle that limits its use. Therefore, a novel protective agent is urgently needed. Enzyme activation recently gained much interest as a new therapeutic strategy. In this context, Alda-1 is a newly emerged molecule in the field of cardioprotection through its activation of aldehyde dehydrogenase 2 enzyme. Aim of the Study:To evaluate the possible protective effect of aldehyde dehydrogenase agonist Alda-1 on doxorubicin induced cardiotoxicity. Material and methods: Twenty-four adult male C57BL/6 mice were divided equally into 4 groups. Group I received intraperitoneal injection of saline. Group II received intraperitoneal injection of Alda-1 (10 mg/kg) daily for 5 days. Group III received a single intraperitoneal injection of DOX (20 mg/kg). Group IV received both DOX and Alda-1 in the same regimen as in groups II and III, Alda-1 was administered 1 day before DOX. All mice were euthanized on the 5th day following DOX administration. Blood samples were collected, hearts were excised and further processed for anatomical, histological and biochemical analysis. Results: DOX administration caused extensive cardiotoxicity as evident by the marked decrease in the heart weight and the extensive myocardial lesions shown by the light and electron microscopic examination. Moreover, biochemical serum markers of cardiac injury (CK-MB &LDH) were markedly elevated. Increased oxidative stress was also encountered as shown by the decreased serum TAC and increased tissue MDA. Furthermore, mitochondrial morphometry showed increased mitochondrial size. However, concomitant administration of Alda-1 with DOX has markedly alleviated the heart injury as shown by the restoration of the heart weight and cardiac architecture together with preservation of the mitochondrial structure. Moreover, Alda-1 has ameliorated the biochemical markers of cardiac injury and the oxidative stress. Conclusion:Alda-1 provides a valuable protective effect against doxorubicin triggered cardiotoxicity.