| Autor: |
Lindeblad M; Toxicology Research Laboratory, Department of Pharmacology, University of Illinois at Chicago, Chicago, Illinois 60612, USA., Kapetanovic IM, Kabirov KK, Dinger N, Mankovskaya I, Morrisey R, Martín-Jiménez T, Lyubimov A |
| Jazyk: |
angličtina |
| Zdroj: |
Drug and chemical toxicology [Drug Chem Toxicol] 2011 Jul; Vol. 34 (3), pp. 300-10. |
| DOI: |
10.3109/01480545.2010.536771 |
| Abstrakt: |
9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 mg/kg/day to CD® rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglobulinemia resulted in a decreased albumin/globulin ratio. Histopathology revealed hepatocellular change consistent with hepatic glycogen deposition. Toxicity studies in dogs did not show treatment-related toxicity at doses as high as 100 mg/kg/day (highest dose tested) administered by capsules for 28 days. No effects on the central nervous system (functional observational battery in rats) or cardiovascular function (safety pharmacology study in telemeterized dogs) were seen. The no observed adverse effect level (NOAEL) in the rat studies was 3 mg/kg/day; however, the adverse effects seen in rats receiving 15 mg/kg/day (the least observed adverse effect level) was a slight, but statistically significant, elevation in fibrinogen and decrease in prothrombin time, which may be a sign of some tendency for increased blood coagulation. The NOAEL in the dog study was at least 100 mg/kg/day. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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