{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:13:18Z","timestamp":1780319598947,"version":"3.54.1"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The effect of antichagasic benznidazole (BZL; 100 mg\/kg body weight\/day, 3 consecutive days, intraperitoneally) on biotransformation systems and ABC transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP-glucuronosyltransferase (UGT1A), glutathione<jats:italic>S<\/jats:italic>-transferases (alpha glutathione<jats:italic>S<\/jats:italic>-transferase [GST-\u03b1], GST-\u03bc, and GST-\u03c0), multidrug-resistance-associated protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney was estimated by Western blotting. Increases in hepatic CYP3A (30%) and GST-\u03bc (40%) and in intestinal GST-\u03b1 (72% in jejunum and 136% in ileum) were detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver from BZL-treated rats were observed without changes in kidney. P-gp and Mrp2 were also increased by BZL in jejunum (170% and 120%, respectively). In ileum, only P-gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlated well with the upregulation of proteins in liver and jejunum. Plasma decay of a test dose of BZL (5 mg\/kg body weight) administered intraduodenally was faster (295%) and the area under the concentration-time curve (AUC) was lower (41%) for BZL-pretreated rats than for controls. The biliary excretion of BZL was higher (60%) in the BZL group, and urinary excretion of BZL did not show differences between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in pretreated rats than in controls. In conclusion, induction of biotransformation enzymes and\/or transporters by BZL could increase the clearance and\/or decrease the intestinal absorption of coadministered drugs that are substrates of these systems, including BZL itself.<\/jats:p>","DOI":"10.1128\/aac.02531-12","type":"journal-article","created":{"date-parts":[[2013,7,23]],"date-time":"2013-07-23T02:15:44Z","timestamp":1374545744000},"page":"4894-4902","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Modulation of Biotransformation Systems and ABC Transporters by Benznidazole in Rats"],"prefix":"10.1128","volume":"57","author":[{"given":"Virginia G.","family":"Perdomo","sequence":"first","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental (CONICET)-Area Fisiolog\u00eda, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (UNR), Rosario, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Rigalli","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Experimental (CONICET)-Area Fisiolog\u00eda, Facultad de Ciencias Bioqu\u00edmicas y Farmac\u00e9uticas (UNR), Rosario, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvina S. 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