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      Acute toxicity of berberine and its correlation with the blood concentration in mice.

      Food and Chemical Toxicology
      Animals, Berberine, administration & dosage, blood, pharmacokinetics, toxicity, Biological Availability, Chromatography, High Pressure Liquid, Drug Administration Routes, Drugs, Chinese Herbal, Female, Lethal Dose 50, Male, Mice, Mice, Inbred ICR, Toxicity Tests, Acute

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          Abstract

          The aim of this study was to investigate the LD(50) (median lethal dosage) of berberine (BBR) through three different routes of injection in mice: intravenous (i.v.) injection, intraperitoneal (i.p.) injection, and intragastric (i.g.) oral administration. The concentration of BBR in blood from their i.g. doses (10.4, 20.8, 41.6, and 83.2 g/kg) and the content relationship of BBR among different injections were analyzed by high-performance liquid chromatography (HPLC). The LD(50) of BBR from i.v. and i.p. injections is 9.0386 and 57.6103 mg/kg, respectively; but no LD(50) was found in the i.g. group. A significant difference in bioavailability was observed between the different routes. Furthermore, the concentration of BBR in the blood from different i.g. doses was also significantly different. However, we discovered an interesting phenomenon indicating that the absorption of BBR by oral administration has a limit, therefore, explaining the difficulty in obtaining an LD(50) of BBR for i.g. injection. From the analysis of BBR content in blood after various administrations, we hypothesized that not only does the concentration of BBR in blood contribute to its acute toxicity, but also the routes of administration may be an important facet that affects this toxicity evaluation. 2010 Elsevier Ltd. All rights reserved.

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