Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Long-Evans Cinnamon (LEC) rat, an animal model for Wilson's disease, is an inbred mutant strain, which because of the genetic copper metabolism disorder develops hepatitis approximately 4 months after birth, followed by chronic hepatitis later in life, and eventually all of the surviving animals from liver injury and hepatitis develop spontaneous hepatocellular carcinomas. This animal model also shows that the generation of reactive oxygen species and the accumulation of oxidative damage in the liver DNA has significantly increased over the lifetime of LEC versus the wild-type Long-Evans Agouti (LEA) rats. Thus, the LEC rats having this genetically induced oxidative condition are proved to be very useful model for the study of endogenous DNA lesions and their relation to spontaneous carcinogenesis. In this study, we tested the hypothesis that differences do exist between these two rat strains in respect to their capacity to repair oxidative DNA base modification, which could explain the elevation of endogenous oxidative damage in the LEC rat liver DNA. We found that both the activity and expression at the protein and RNA levels of major DNA glycosylases, endonuclease III and 8-oxoguanine DNA-glycosylase, which initiate the excision and repair of oxidized bases, were significantly altered during the acute (16-18 weeks) and early chronic (24 weeks) phases of hepatitis. Enzyme levels were restored in the later period of chronic hepatitis (week 40) in the LEC rat liver as compared with the age-matched LEA rats. This early reduction in the capacity to repair oxidative DNA base damage could have contributed to the accumulation of mutagenic adducts in liver DNA. These findings show for the first time in an animal model that acute hepatitis impairs the repair of oxidative DNA base damage and strongly suggest that the repair of endogenous DNA adducts plays a critical role in the development of spontaneous hepatocellular carcinoma in LEC rats.
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PMID:Evidence of alterations in base excision repair of oxidative DNA damage during spontaneous hepatocarcinogenesis in Long Evans Cinnamon rats. 1463 94

The One Health principle recognizes that human health, animal health, and environmental health are inextricably linked. An excellent example is the study of naturally occurring copper toxicosis in dogs to help understand human disorders of copper metabolism. Besides the Bedlington terrier, where copper toxicosis is caused by a mutation in the COMMD1 gene, more complex hereditary forms of copper-associated hepatitis were recognized recently in other dog breeds. The Labrador retriever is one such breed, where an interplay between genetic susceptibility and exposure to copper lead to clinical copper toxicosis. Purebred dog populations are ideal for gene mapping studies, and because genes involved in copper metabolism are highly conserved across species, newly identified gene mutations in the dog may help unravel the genetic complexity of different human forms of copper toxicosis. Furthermore, increasing knowledge with respect to diagnosis and treatment strategies will benefit both species.
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PMID:New canine models of copper toxicosis: diagnosis, treatment, and genetics. 2475 44