Chronic effects of losartan on the muscles and the serologic profiles of mdx mice
| Autor: | Eun-Mi Lee, Jin-Kyu Park, Sang-Hyeob Kim, Myeong-Mi Lee, Eun-Joo Lee, Dae-Yong Kim, Soo-Eun Sung, Kyu-Shik Jeong, Ah Young Kim |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Duchenne muscular dystrophy Administration Oral Losartan General Biochemistry Genetics and Molecular Biology Mice Transforming Growth Factor beta Fibrosis Internal medicine medicine Animals General Pharmacology Toxicology and Pharmaceutics Muscle Skeletal Receptor biology business.industry Therapeutic effect General Medicine Transforming growth factor beta medicine.disease Angiotensin II Mice Inbred C57BL Muscular Dystrophy Duchenne Treatment Outcome Endocrinology Mice Inbred mdx cardiovascular system biology.protein business Angiotensin II Type 1 Receptor Blockers Biomarkers hormones hormone substitutes and hormone antagonists medicine.drug Transforming growth factor |
| Zdroj: | Life Sciences. 143:35-42 |
| ISSN: | 0024-3205 |
| Popis: | Aims Losartan, an angiotensin II type 1 receptor blocker, attenuates transforming growth factor-β (TGF-β) signaling, which inhibits myogenic regeneration. Although many researchers have demonstrated that losartan has anti-fibrotic and protective effects on cardiac and skeletal muscles, for long-term administration to treat dystrophic disorders, it is essential to demonstrate not only the therapeutic effects of losartan on muscles but also its effects on other organs and on blood biochemistry. Main methods Mdx mice, an animal model of Duchenne muscular dystrophy (DMD), were fed losartan dissolved in tap water. After 44 weeks, the skeletal (gastrocnemius), cardiac, and diaphragm muscles of mdx mice were removed. Tissue and blood samples were collected from all experimental animals. Effects of losartan on muscle regeneration, fibrosis, and blood enzymatic profiles were evaluated. Key findings In histopathological findings and serum biochemistry analyses, chronic losartan administration showed muscular protective effects and inhibited fibrosis in skeletal (gastrocnemius), cardiac, and diaphragmatic muscles. In addition, losartan had no effects on other solid organs. Interestingly, losartan had beneficial effects on serum HDL ratio. Significance This study demonstrates the therapeutic effects of losartan on muscles and its effects on other organs and on blood biochemistry. In conclusion, our results provide useful information for consideration of chronic losartan administration be as a treatment of DMD. |
| Databáze: | OpenAIRE |
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