title: Evaluation of the safety and bioactivity of purified and semi-purified glucoraphanin.
abstract: The anti-carcinogenic effects of broccoli have been attributed to sulforaphane, the hydrolysis product of glucoraphanin (GRP). Here we determined if purified GRP, in the absence of the plant-derived hydrolyzing enzyme myrosinase, could affect pulmonary and hepatic ethoxyresorufin O-deethylase (EROD) and/or NAD(P)H-quinone oxidoreductase 1 (NQO1) activity. Male F344 rats were administered semi-synthetic, semi-purified or purified GRP (240 mg/kg: 550 micromol/kg rat daily for 4 days) by gavage. Hepatic and pulmonary NQO1 activity increased ( approximately 20%), but not EROD. Varying doses of semi-purified GRP (30, 60, or 120 mg/kg rat daily for 4 days) again caused no change in EROD activity, although a dose-dependent increase in NQO1 was seen. Urinary excretion of mercapturic acids showed no difference between preparations, and recovery increased with decreasing dose. Histopathologic examination revealed no abnormal tissues other than cecum, where inflammation was dose dependent; mild at 120 mg/kg and severe at 240 mg/kg, a greatly supra-physiological dose. We conclude that GRP 30-60 mg/kg p.o. is safe and effectively enhances NQO1 in all tissues evaluated.
authors.affiliation: Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, Illinois 61801, USA.
authors.forename: R-H
authors.initials: RH
authors.lastname: Lai
authors.forename: A-S
authors.initials: AS
authors.lastname: Keck
authors.forename: M A
authors.initials: MA
authors.lastname: Wallig
authors.forename: L G
authors.initials: LG
authors.lastname: West
authors.forename: E H
authors.initials: EH
authors.lastname: Jeffery
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D001937:Brassica / Q000737:chemistry; D002432:Cecum / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification; D005961:Glucosinolates / Q000009:adverse effects / Q000302:isolation & purification / Q000494:pharmacology*; D007096:Imidoesters / Q000009:adverse effects / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010084:Oxidation-Reduction; D010091:Oximes; D051381:Rats; D011916:Rats, Inbred F344; D012639:Seeds / Q000737:chemistry; D013454:Sulfoxides