Studies of the Pancreatotoxicity of 1-cyano-2-hydroxy-3-butene

Maher, Maurica (1991) Studies of the Pancreatotoxicity of 1-cyano-2-hydroxy-3-butene. Masters thesis, Memorial University of Newfoundland.

[img] [English] PDF (Migrated (PDF/A Conversion) from original format: (application/pdf)) - Accepted Version
Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.

Download (12Mb)
  • [img] [English] PDF - Accepted Version
    Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission.
    (Original Version)

Abstract

A racemic mixture of (R)- and (S)-1-cyano-2-hydroxy-3-butene (CHB) was synthesized using 1,3-butadiene as a starting compound. The effects of CHB on pancreatic non-protein thiol and glutathione S-transferase activity were investigated in adult male rats when administered orally in olive oil at a dose of 200 mg/kg. At 4 hours after dosing, pancreatic non-protein thiol content was depleted but rebounded at 24 hours to 3 times control values. At 120 hours after dosing, pancreatic non-protein thiol levels were still elevated over control levels. Hepatic non-protein thiol levels were greater than control levels at 4 hours after dosing, but were not significantly different from control values at 24 and 120 hours after dosing. The pattern of pancreatic non-protein thiol changes with synthetic CHB resembles that reported with the natural (S)- isomer of CHB. -- Glutathione S-transferase activity was decreased at 4 hours following CHB treatment in the rat pancreas, and elevated at 24 hours. Hepatic glutathione S-transferase activity was not altered by CHB treatment. -- The effect of increasing intraduodenal doses of CHB (25-200 mg/kg) on rat pancreatic juice secretion and bile secretion was investigated in conscious rats. CHB was administered intraduodenally and caused a stimulation in pancreatic juice secretion followed by a return to control values at the lower doses. At higher doses, CHB causes the same early stimulation, but is followed by a depression of pancreatic juice flow. All doses of CHB administered resulted in a dose-dependent decrease of protein concentration in pancreatic juice. -- CHB caused the pancreata of treated rats to become oedematous, a condition also seen in certain forms of acute pancreatitis. The severity of the oedema was dose-dependent and could be visually detected. The exudate collected from these pancreata had protein concentrations comparable to plasma. -- Radioactive CHB ([¹⁴C]) was synthesized and administered to rats intraduodenally that were also fitted with biliary fistulae. CHB was found to be excreted over 8 hours in the bile and urine, with higher amounts excreted in the urine. Little [¹⁴C] was detected in the pancreas and kidneys, but did accumulate in the adipose tissue (7.7%) and in the liver (5.5%). -- These results indicate that synthetic CHB is a powerful and selective pancreatotoxin and the present data are not incompatible with a glutathione-mediated mechanism, as is known to occur with other unsaturated nitriles.

Item Type: Thesis (Masters)
URI: http://research.library.mun.ca/id/eprint/4069
Item ID: 4069
Additional Information: Bibliography: leaves 151-158.
Department(s): Science, Faculty of > Biochemistry
Date: 1991
Date Type: Submission
Library of Congress Subject Heading: Pancreas; Cruciferae; Nitriles--Toxicology; Feeds--Contamination; Butene--Toxicology

Actions (login required)

View Item View Item

Downloads

Downloads per month over the past year

View more statistics