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A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats

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Title: A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats
Authors: Mukai, Takahiro / Mera, Kunihiro / Nishida, Koyo / Nakashima, Mikiro / Sasaki, Hitoshi / Sakaeda, Toshiyuki / Nakamura, Junzo
Issue Date: Nov-2002
Publisher: Pharmaceutical Society of Japan
Citation: Biological & Pharmaceutical Bulletin v.25(11) p.1494-1497, 2002
Abstract: Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition.
Keywords: animal model / liver damage / carbon tetrachloride / liver targeting / rat
URI: http://hdl.handle.net/10069/8379
ISSN: 09186158
DOI: 10.1248/bpb.25.1494
PubMed ID: 12419969
Relational Links: http://dx.doi.org/10.1248/bpb.25.1494
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/8379

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