We have previously reported that CYP3A cross-links with polyubiquitinated proteins in microsomes from nicardipinetreated rats in a process that is distinct from classical polyubiquitination. To further examine the role of the proteasome in CYP3A degradation, we investigated the effects of proteasome inhibitors lactacystin, MG132, proteasome inhibitor 1, and hemin in primary cultures of rat and human hepatocytes. With the exception of hemin, these agents increased the total pool of ubiquitinated proteins in microsomes isolated from rat hepatocytes, indicating that lactacystin, MG132, and proteasome inhibitor 1 effectively inhibited the proteasome in these cells.
Effect of acute toxicity and chronic toxicity on attapulgite for animal was studied by Kunming mice and SD rats experiment through administering intragastrically with large dose of attapulgite suspension. The results showed that the mice were normal and grew well, and they did not appear death and toxicity symptoms when they received the same amount as 286 times of the adult dose, indicating that attapulgite mineral powders did not contain acute toxicity and administering intragastrically with large dose of attapulgite suspension had no obvious influence on blood environment and normal growth of rats, and attapulgite did not contain chronic toxicity.
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