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Long-Acting Thioredoxin Ameliorates Doxorubicin-Induced Cardiomyopathy via Its Anti-Oxidative and Anti-Inflammatory Action
| Content Provider | MDPI |
|---|---|
| Author | Murata, Ryota Watanabe, Hiroshi Nosaki, Hiroto Nishida, Kento Maeda, Hitoshi Nishida, Motohiro Maruyama, Toru |
| Copyright Year | 2022 |
| Description | 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. |
| Starting Page | 562 |
| e-ISSN | 19994923 |
| DOI | 10.3390/pharmaceutics14030562 |
| Journal | Pharmaceutics |
| Issue Number | 3 |
| Volume Number | 14 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-03-03 |
| Access Restriction | Open |
| Subject Keyword | Pharmaceutics Peripheral Vascular Disease Albumin Fusion Thioredoxin Oxidative Stress Inflammation Cardiomyopathy Doxorubicin |
| Content Type | Text |
| Resource Type | Article |
