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Pharmaceuticsに論文が掲載されました。（薬剤性心不全に対する血中滞留型チオレドキシンの有効性）

2022/03/30

Pharmaceuticsに論文が掲載されました。（薬剤性心不全に対する血中滞留型チオレドキシンの有効性）

（九州大学・生理研の西田基宏教授との共同研究）

Murata R, Watanabe H, Nosaki H, Nishida K, Maeda H, Nishida M, Maruyama T.
Long-Acting Thioredoxin Ameliorates Doxorubicin-Induced Cardiomyopathy via Its Anti-Oxidative and Anti-Inflammatory Action.
Pharmaceutics. 2022 Mar 3;14(3):562. doi: 10.3390/pharmaceutics14030562.

Abstract

Although the number of patients with heart failure is increasing, a sufficient treatment agent has not been established. Oxidative stress and inflammation play important roles in the development of myocardial remodeling. When thioredoxin (Trx), an endogenous anti-oxidative and inflammatory modulator with a molecular weight of 12 kDa, is exogenously administered, it disappears rapidly from the blood circulation. In this study, we prepared a long-acting Trx, by fusing human Trx (HSA-Trx) with human serum albumin (HSA) and evaluated its efficacy in treating drug-induced heart failure. Drug-induced cardiomyopathy was created by intraperitoneally administering doxorubicin (Dox) to mice three times per week. A decrease in heart weight, increased myocardial fibrosis and markers for myocardial damage that were observed in the Dox group were suppressed by HSA-Trx administration. HSA-Trx also suppressed the expression of atrogin-1 and myostatin, myocardial atrophy factors in addition to suppressing oxidative stress and inflammation. In the Dox group, a decreased expression of endogenous Trx in cardiac tissue and an increased expression of macrophage migration inhibitory factor were observed, but these changes were restored to normal levels by HSA-Trx administration. These findings suggest that HSA-Trx improves the pathological condition associated with Dox-induced cardiomyopathy by its anti-oxidative/anti-inflammatory and myocardial atrophy inhibitory action.

Keywords: albumin fusion; cardiomyopathy; doxorubicin; inflammation; oxidative stress; thioredoxin.