Inhibition of tumor necrosis factor alpha secretion and prevention of liver injury in ethanol-fed rats by antisense oligonucleotides
Author | dc.contributor.author | Ponnappa, Biddanda C. | |
Author | dc.contributor.author | Israel Jacard, Yedy | es_CL |
Author | dc.contributor.author | Aini, María | es_CL |
Author | dc.contributor.author | Zhou, Feng | es_CL |
Author | dc.contributor.author | Russ, Rachel | es_CL |
Author | dc.contributor.author | Cao, Qing-na | es_CL |
Author | dc.contributor.author | Yiyang, Hu | es_CL |
Author | dc.contributor.author | Rubin, Raphael | es_CL |
Admission date | dc.date.accessioned | 2007-06-05T19:55:00Z | |
Available date | dc.date.available | 2007-06-05T19:55:00Z | |
Publication date | dc.date.issued | 2005-02-15 | |
Cita de ítem | dc.identifier.citation | BIOCHEMICAL PHARMACOLOGY | en |
Identifier | dc.identifier.issn | 0006-2952 | |
Identifier | dc.identifier.uri | https://repositorio.uchile.cl/handle/2250/120429 | |
Abstract | dc.description.abstract | Elevated serum tumor necrosis factor alpha JNF-alpha) levels predict mortality in patients with alcoholic liver disease. Administration of anti-TNF-alpha antibodies, obliteration of Kupffer cells or gut sterilization protect against ethanol-induced hepatocellular injury in animal models. In this study, we evaluated the in vivo efficacy of an antisense phosphorothioate oligodeoxynucleotide (S-ODN) targeted against TNF-alpha mRNA (TJU-2755). Naive rats that were administered TJU-2755 (10 mg/(kg body weight (BW)/day) for 2 days) in the free form were challenged with LPS to induce TNF-alpha secretion. Antisense TJU-2755 treatment reduced serum TNF-a levels by 62%. A comparison of the efficacies of mismatched and random S-ODNs with that of TJU-2755 showed that some non-specific inhibition might accompany the sequence-specific effects of TJU-2755. To optimize the targeting of the S-ODN, TJU-2755 was encapsulated in pH-sensitive liposomes for in vivo delivery to macrophages. The efficacy of liposome-encapsulated TJU-2755 was assessed in ethanol-fed animals that were administered LPS to induce liver injury. Liposomal delivery of TJU-2755 allowed a much lower dose (1.9 mg/kg BW/day, for 2 days) of the S-ODN to reduce LPS-induced serum TNF-alpha (by 54%) and liver injury (by 60%) in ethanol-fed rats. These data indicate that liposome-encapsulated S-ODNs targeted against TNF-a have therapeutic potential in the treatment of alcoholic liver disease. | en |
Lenguage | dc.language.iso | en | en |
Publisher | dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | en |
Keywords | dc.subject | INDUCED HEPATIC-INJURY | en |
Título | dc.title | Inhibition of tumor necrosis factor alpha secretion and prevention of liver injury in ethanol-fed rats by antisense oligonucleotides | en |
Document type | dc.type | Artículo de revista |
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