Effect of experimental diabetes and insulin replacement on intestinal metabolism and excretion of 4-nitrophenol in rats

Emil Fischer, Attila Almási, Sztojan Bojcsev, Tamás Fischer, Noémi Piroska Kovács, Pál Perjési

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Luminal appearance of 4-nitrophenol (PNP) metabolites (4-nitrophenol-β-glucuronide (PNP-G) and 4-nitrophenol-sulfate (PNP-S)) and activity of the related metabolic enzymes have been investigated in control and experimental diabetic rats. Experimental diabetes was induced by administration of streptozotocin (65 mg/kg i.v.). PNP (500 μmol/L) was luminally perfused in the small intestine and the metabolites were determined in the perfusion solution. Effect of insulin replacement was also investigated in the diabetic rats. It was found that experimental diabetes increased the luminal appearance of PNP-G, which could be completely compensated by rapid-acting insulin administration (1 U/kg i.v.). Activities of the enzymes involved in PNP-G production (UDP-glucuronyltransferase and β-glucuronidase) were also elevated; however, these changes were only partially compensated by insulin. Luminal appearance of PNP-S was not significantly changed by administration of streptozotocin and insulin. Activities of the enzymes of PNP-S production (sulfotransferases and arylsulfatases) did not change in the diabetic rats. The results indicate that experimental diabetes can provoke changes in intestinal drug metabolism. It increased intestinal glucuronidation of PNP but did not influence sulfate conjugation. No direct correlation was found between the changes of metabolic enzyme activities and the luminal appearance of the metabolites.

Original languageEnglish
Pages (from-to)459-464
Number of pages6
JournalCanadian journal of physiology and pharmacology
Volume93
Issue number6
DOIs
Publication statusPublished - Feb 26 2015

Keywords

  • 4-nitrophenol
  • Experimental diabetes
  • Glucuronidation
  • Insulin
  • Intestinal drug metabolism
  • Sulfation

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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