Astaxanthin extenuates the inhibition of aldehyde dehydrogenase and Klotho protein expression in cyclophosphamide-induced acute cardiomyopathic rat model.

Abstract

This study evaluated the mechanistic sequel ofaldehyde dehyrogenase (ALDH2) and Klotho protein in cyclophosphamide (CP)-induced cardiotoxicity in rats and the protective effect of astaxanthin (AST) against that sequel. A total of 40male Wistar albino ratswere divided into fourgroups of 10 animals each: Group 1wasinjected intraperitoneally(i.p.) with normal saline for 10successive days. Group 2 was injected with normal saline for 5days before and after a single dose of CP (200mg/kg, i.p.). Group 3 received AST (50mg/kg/day, i.p.) for 10days. Group 4 received CP as group 2 and AST as group 3. After the last dose of the treatment protocol, serum was separated to measure cardiotoxicity indices and the left ventricle was then dissected for mRNA and protein expression studies and histopathological examinations. Treatment with CP significantly increased serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and troponin, while significantly decreased soluble α Klotho protein and caused histopathological lesions in cardiac tissues. In cardiac tissues, CP significantly decreased gene expression of ALDH2, Klotho protein, mTOR, IGF, AKT, AMPK, BCL2, but significantly increased expression of BAX and caspase-8. Interestingly, administration of AST in combination with CP completely reversed all the biochemical, histopathological and gene expression changes induced by CP to the control values. The current study suggests that inhibition of ALDH2, Klotho protein, mTOR, and AMPK signals in cardiac tissues may contribute to CP-induced acute cardiomyopathy. AST supplementation attenuates CP-induced cardiotoxicity by modulating ALDH2 and Klotho protein expression in heart tissues, along with its downstream apoptosis effector markers.