| Autor: |
Shruti Mohan, Louis-Antoine Barel, Djamal Eddine Benrahla, Bernard Do, Qiyue Mao, Hiroaki Kitagishi, Michael Rivard, Roberto Motterlini, Roberta Foresti |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Pharmacological Research, Vol 191, Iss , Pp 106770- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1096-1186 |
| DOI: |
10.1016/j.phrs.2023.106770 |
| Popis: |
Metal carbonyls have been developed as carbon monoxide-releasing molecules (CO-RMs) to deliver CO for therapeutic purposes. The manganese-based CORM-401 has been recently reported to exert beneficial effects in obese animals by reducing body weight gain, improving glucose metabolism and reprogramming adipose tissue towards a healthy phenotype. Here, we report on the synthesis and characterization of glyco-CORMs, obtained by grafting manganese carbonyls on dextrans (70 and 40 kDa), based on the fact that polysaccharides facilitate the targeting of drugs to adipose tissue. We found that glyco-CORMs efficiently deliver CO to cells in vitro with higher CO accumulation in adipocytes compared to other cell types. Oral administration of two selected glyco-CORMs (5b and 6b) resulted in CO accumulation in various organs, including adipose tissue. In addition, glyco-CORM 6b administered for eight weeks elicited anti-obesity and positive metabolic effects in mice fed a high fat diet. Our study highlights the feasibility of creating carriers with multiple functionalized CO-RMs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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