US EPA

5360230 

Journal Article 

Effects of 1-isothiocyanato-3-(methylsulfinyl)-propane on xenobiotic metabolizing enzymes in rats 

Kore, AM; Jeffery, EH; Wallig, MA 

1993 

Yes 

Food and Chemical Toxicology
ISSN: 0278-6915
EISSN: 1873-6351 

Elsevier 

31 

10 

723-729 

English 

8225130 

10.1016/0278-6915(93)90143-M 

WOS:A1993ME10900005 

The glucosinolate hydrolysis product 1-isothiocyanato-3-(methylsulfinyl)-propane (IMSP), also known as iberin, is consumed in the average human (US) diet at approximately 1 mumol/kg/day. The chemoprotective effects observed with the consumption of cruciferous vegetables may be due to the presence of specific glucosinolate hydrolysis products either within the crucifers, or formed after ingestion of the crucifers. The mechanism of chemoprotection may be through selective induction of components of Phase II xenobiotic metabolizing enzymes. The influence of repeated administration of low concentrations of IMSP by gavage on components of Phase I and Phase II xenobiotic metabolizing systems was examined in the liver and small intestine of male Fischer 344 rats. Doses of 1, 10 and 100 mumol IMSP/kg, administered by gavage for 7 days, did not alter weight gain, or hepatic and renal weights, relative to body weight, and did not cause any histological lesions. Intestinal glutathione S-transferase (GST) activity and NAD(P)H:quinone reductase (QR) activities were significantly elevated to 3.1 and 8.1 times control values, respectively, at the 100 mumol/kg dose only. The administration of IMSP at 1, 10 or 100 mumol/kg had no significant effect on hepatic Phase I enzymes activities (cytochrome P-450 concentrations, ethoxycoumarin O-deethylase [ECD] and aminopyrine N-demethylase [AND] activities) or Phase II enzyme activities (GST, QR and UDP-glucuronosyltransferase [UDP-GT] activities towards 1-naphthol or 4-hydroxybiphenyl), at any of the doses tested and no effect on intestinal enzyme activities at doses below 100 mumol IMSP/kg. It is concluded that IMSP does not have a significant influence on induction of the Phase I or Phase II xenobiotic metabolizing enzymes in rats when tested at doses approximating those found in the human diet. 

1-naphthol GT = microsomal UDP-GT activity towards 1-naphthol; 4-dinitrobenzene; 4-HBP = 4-hydroxybiphenyl; 4-HBP GT = microsomal UDP-GT activity towards 4-hydroxybiphenyl; 6-dichlorophenolindophenol; AND = aminopyrine N-demethylase; ANOVA = analysis of variance; CDNB = 1-chloro-2; CYP = cytochrome P-450 protein; cyt P450 = cytochrome P-450; DPIP = 2; ECD = ethoxycoumarin O-deethylase; GST = glutathione S-transferase; IMSB = 1-isothiocyanato-4-(methylsulfiny)-butane; IMSP = 1-isothiocyanato-3-(methylsulfinyl)-propane (CAS No. 505-44-2); MSBN = 3-(methylsulfinyl)-butanenitrile (CAS No. 61121-65-1); QR = NAD(P)H:quinone reductase; UDP-GT = uridine diphosphate glucurono-syltransferase