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• W2289668897 abstract "Pentavalent antimonial (Sb 5+ ) drugs such as meglumine antimoniate (MA) are the mainstay treatment of leishmaniases in developing countries. The effects of these compounds on drug-metabolizing enzymes have not been characterized and their potential pharmacokinetic interactions with other drugs are therefore unknown. The present study investigated whether treatment with MA (300 mg Sb 5+ /kg body weight/day, subcutaneously) for 24 days affected the activities of cytochrome P450 (CYP)1A (ethoxyresorufin- O-deethylase), CYP2A5 (coumarin 7-hydroxylase), CYP2E1 ( p-nitrophenol-hydroxylase), CYP2B9/10 (benzyloxy-resorufin- O-debenzylase), or CYP3A11 (erythromycin- N-demethylase) in the livers of Swiss Webster (SW) and DBA-2 male and female mice. The results showed that CYP2A5-, CYP2E1-, and CYP3A11-catalyzed reactions were unaffected by MA treatment. A decrease in CYP2B9/10 activity was noted in DBA-2 females (but not males) and was not observed in SW males or females. However, repeated MA administration reduced mouse liver CYP1A activity. CYP1A2 messenger RNA (mRNA) levels were not affected by MA and in vitro exposure of mouse liver microsomes to Sb 3+ and Sb 5+ did not reduce CYP1A activity. These findings suggested that in vivo treatment with Sb 5+ drugs depressed CYP1A activity, without downregulating CYP1A2 mRNA expression. Since in vitro treatment of liver microsomes failed to inhibit CYP1A activity, this effect may require intact cells." @default.
• W2289668897 created "2016-06-24" @default.
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• W2289668897 date "2016-07-11" @default.
• W2289668897 modified "2023-09-24" @default.
• W2289668897 title "In vivo and in vitro effects of pentavalent antimony on mouse liver cytochrome P450s" @default.
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• W2289668897 doi "https://doi.org/10.1177/0960327116637110" @default.
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