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Effect of glucagon-like peptide 2 on hepatic, renal, and intestinal disposition of 1-chloro-2,4-dinitrobenzene.
Drug Metab Dispos. 2012 Jul; 40(7):1252-8.DM

Abstract

The ability of the liver, small intestine, and kidney to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for multidrug resistance-associated protein 2 (Mrp2), was assessed in rats treated with glucagon-like peptide 2 (GLP-2, 12 μg/100 g b.wt. s.c. every 12 h for 5 consecutive days). An in vivo perfused jejunum model with simultaneous bile and urine collection was used. A single intravenous dose of 30 μmol/kg b.wt. 1-chloro-2,4-dinitrobenzene (CDNB) was administered, and its conjugate, DNP-SG, and dinitrophenyl cysteinyl glycine (DNP-CG), resulting from the action of γ-glutamyltransferase on DNP-SG, were determined in bile, intestinal perfusate, and urine by high-performance liquid chromatography. Tissue content of DNP-SG was also assessed in liver, intestine, and kidneys. Biliary excretion of DNP-SG+DNP-CG was decreased in GLP-2 rats with respect to controls. In contrast, their intestinal excretion was substantially increased, whereas urinary elimination was not affected. Western blot and real-time polymerase chain reaction studies revealed preserved levels of Mrp2 protein and mRNA in liver and renal cortex and a significant increase in intestine in response to GLP-2 treatment. Tissue content of DNP-SG detected 5 min after CDNB administration was decreased in liver, increased in intestine, and unchanged in kidney in GLP-2 versus control group, consistent with GLP-2-induced down-regulation of expression of glutathione transferase (GST) Mu in liver and up-regulation of GST-Alpha in intestine at both protein and mRNA levels. In conclusion, GLP-2 induced selective changes in hepatic and intestinal disposition of a common GST and Mrp2 substrate administered systemically that could be of pharmacological or toxicological relevance under therapeutic treatment conditions.

Authors+Show Affiliations

Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Suipacha 570, S2002LRL Rosario, Argentina.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22453052

Citation

Villanueva, Silvina S M., et al. "Effect of Glucagon-like Peptide 2 On Hepatic, Renal, and Intestinal Disposition of 1-chloro-2,4-dinitrobenzene." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 40, no. 7, 2012, pp. 1252-8.
Villanueva SS, Perdomo VG, Ruiz ML, et al. Effect of glucagon-like peptide 2 on hepatic, renal, and intestinal disposition of 1-chloro-2,4-dinitrobenzene. Drug Metab Dispos. 2012;40(7):1252-8.
Villanueva, S. S., Perdomo, V. G., Ruiz, M. L., Rigalli, J. P., Arias, A., Luquita, M. G., Vore, M., Catania, V. A., & Mottino, A. D. (2012). Effect of glucagon-like peptide 2 on hepatic, renal, and intestinal disposition of 1-chloro-2,4-dinitrobenzene. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 40(7), 1252-8. https://doi.org/10.1124/dmd.111.044339
Villanueva SS, et al. Effect of Glucagon-like Peptide 2 On Hepatic, Renal, and Intestinal Disposition of 1-chloro-2,4-dinitrobenzene. Drug Metab Dispos. 2012;40(7):1252-8. PubMed PMID: 22453052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of glucagon-like peptide 2 on hepatic, renal, and intestinal disposition of 1-chloro-2,4-dinitrobenzene. AU - Villanueva,Silvina S M, AU - Perdomo,Virginia G, AU - Ruiz,María L, AU - Rigalli,Juan P, AU - Arias,Agostina, AU - Luquita,Marcelo G, AU - Vore,Mary, AU - Catania,Viviana A, AU - Mottino,Aldo D, Y1 - 2012/03/27/ PY - 2012/3/29/entrez PY - 2012/3/29/pubmed PY - 2013/1/18/medline SP - 1252 EP - 8 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab Dispos VL - 40 IS - 7 N2 - The ability of the liver, small intestine, and kidney to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for multidrug resistance-associated protein 2 (Mrp2), was assessed in rats treated with glucagon-like peptide 2 (GLP-2, 12 μg/100 g b.wt. s.c. every 12 h for 5 consecutive days). An in vivo perfused jejunum model with simultaneous bile and urine collection was used. A single intravenous dose of 30 μmol/kg b.wt. 1-chloro-2,4-dinitrobenzene (CDNB) was administered, and its conjugate, DNP-SG, and dinitrophenyl cysteinyl glycine (DNP-CG), resulting from the action of γ-glutamyltransferase on DNP-SG, were determined in bile, intestinal perfusate, and urine by high-performance liquid chromatography. Tissue content of DNP-SG was also assessed in liver, intestine, and kidneys. Biliary excretion of DNP-SG+DNP-CG was decreased in GLP-2 rats with respect to controls. In contrast, their intestinal excretion was substantially increased, whereas urinary elimination was not affected. Western blot and real-time polymerase chain reaction studies revealed preserved levels of Mrp2 protein and mRNA in liver and renal cortex and a significant increase in intestine in response to GLP-2 treatment. Tissue content of DNP-SG detected 5 min after CDNB administration was decreased in liver, increased in intestine, and unchanged in kidney in GLP-2 versus control group, consistent with GLP-2-induced down-regulation of expression of glutathione transferase (GST) Mu in liver and up-regulation of GST-Alpha in intestine at both protein and mRNA levels. In conclusion, GLP-2 induced selective changes in hepatic and intestinal disposition of a common GST and Mrp2 substrate administered systemically that could be of pharmacological or toxicological relevance under therapeutic treatment conditions. SN - 1521-009X UR - https://www.unboundmedicine.com/medline/citation/22453052/Effect_of_glucagon_like_peptide_2_on_hepatic_renal_and_intestinal_disposition_of_1_chloro_24_dinitrobenzene_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=22453052 DB - PRIME DP - Unbound Medicine ER -