Protection from spontaneous hepatocellular damage by N-benzyl-D-glucamine dithiocarbamate in Long-Evans Cinnamon rats, an animal model of Wilson's disease
| Autor: | Akira Yasutake, Akinori Shimada, Tadashi Okawara, Yorishige Imamura, Hideaki Shimada, Morio Kiyozumi, Makiko Takahashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Bilirubin Urinary system Spleen Toxicology Lesion chemistry.chemical_compound Hepatolenticular Degeneration Thiocarbamates Internal medicine medicine Animals Humans Sorbitol Rats Long-Evans Chelating Agents Pharmacology Kidney Dose-Response Relationship Drug business.industry Body Weight Penicillamine medicine.disease Rats Wilson's disease Disease Models Animal Endocrinology medicine.anatomical_structure Long-Evans Cinnamon rats Liver chemistry N-benzyl-D-glucamine dithiocarbamate Toxicity Female medicine.symptom business Copper medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 202(1):59-67 |
| ISSN: | 0041-008X |
| Popis: | The Long–Evans Cinnamon (LEC) rat is a mutant strain that accumulates excessive tissue copper (Cu) and models the clinical symptoms and biological features of Wilson's disease in humans. We compared the effects of three metal chelating agents, N -benzyl- d -glucamine dithiocarbamate (BGD), d -penicillamine (D-PEN), and triethylenetetramine (TETA), on the biliary and urinary excretions of Cu using LEC rats. The animals were treated ip with each chelating agent (1 mmol/kg body weight) and then the bile and urine samples were collected for 3 h. Because single treatment with BGD markedly stimulated biliary excretion of Cu, the protective effect of repeated BGD injection on spontaneous hepatocellular damage was further examined. Separate groups received two weekly injections of BGD starting at 11 weeks of age and were compared to saline-injected controls. Serum alanine aminotransferase (ALT) activity and bilirubin level were significantly increased in control LEC rats by 19 weeks of age and histopathological analysis demonstrated extensive hepatic damage in these rats. However, repeated BGD injections prevented the increases in serum ALT and bilirubin and blocked the histopathological changes in the liver. Furthermore, although Cu rapidly accumulated in the liver, kidney, spleen, and serum of control LEC rats during the test period, repeated BGD injection largely prevented these increases. These results indicate that BGD treatment is effective in blocking excessive Cu accumulation in LEC rats that, in turn, provides protection from spontaneous liver damage. |
| Databáze: | OpenAIRE |
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