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Title:The Isolation and Evaluation of Biological Effects of the Glucosinolate Hydrolysis Product 1-Isothiocyanato-3-(methylsulfinyl)-Propane
Author(s):Kore, Anita Maureen
Doctoral Committee Chair(s):Beasley, V.R.,
Department / Program:Veterinary Medical Science
Discipline:Veterinary Medical Science
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Health Sciences, Toxicology
Agriculture, Animal Culture and Nutrition
Health Sciences, Nutrition
Abstract:1-Isothiocyanato-3-(methylsulfinyl)-propane (IMSP) is a glucosinolate hydrolysis product formed from 3-methylsulfinylpropylglucosinolate when crucifers are eaten. The four most commonly consumed crucifers (cabbage, Brussels sprouts, cauliflower, and broccoli) have been shown to contain high concentrations of 3-methylsulfinylpropylglucosinolate, resulting in an estimated mean human intake of IMSP of 1 $\mu$mol/kg/day. Due to difficulties in obtaining purified compounds, methods were developed for the high yield purification of IMSP and related compounds from Lesquerella and broccoli seeds. The procedure used solvent extraction of autolyzed defatted seed meals, followed by hydrolysis product purification using gel filtration chromatography and reversed-phase HPLC.
The toxic effects of intragastrically administered IMSP were unknown. F344 rats were administered IMSP by gavage at 0.1, 0.3, 0.6, 1.0 and 2.0 mmol/kg and killed at 4, 24, and 72 hr post-dosing. Multifocal hemorrhages and erosions of the glandular portion of the stomach were grossly and histologically evident after 4 hr at doses above 0.1 mmol/kg, with severity increasing with dose, and lesions resolved by 72 hours in all but the 2 mmol/kg group. No significant lesions were observed in other tissues. No physiologically significant clinical chemistry changes were observed. Urine collected after a 1 mmol/kg dose of IMSP contained the intact compound, demonstrating that IMSP is absorbed from the gastrointestinal tract.
Several epidemiologic studies have identified a correlation between crucifer consumption and decreased incidence of colorectal cancer in humans. IMSP may be chemoprotective through the induction of xenobiotic metabolizing systems in the liver and small intestine. Doses of 1, 10, and 100 $\mu$mol IMSP/kg were administered by gavage for 7 days to F344 rats. Intestinal glutathione S-transferase and NAD(P)H:quinone reductase were significantly elevated 3.1- and 8.1-fold, respectively, at the 100 $\mu$mol/kg dose only. The administration of IMSP had no significant effect on hepatic Phase I or Phase II enzymes, and no effect on intestinal enzyme activities at doses below 100 $\mu$mol IMSP/kg. IMSP does not appear to induce xenobiotic metabolizing enzymes in rats at doses equivalent to those found in the human diet.
Issue Date:1992
Description:256 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1992.
Other Identifier(s):(UMI)AAI9305588
Date Available in IDEALS:2014-12-17
Date Deposited:1992

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