Efficacyof Sulforaphane in EradicatingHelicobacter pyloriin HumanGastric Xenografts Implanted in NudeMice

Abstract

Sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli sprouts, has shown in vitro activity against Helicobacter pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by using human gastric xenografts in nude mice. H. pylori was completely eradicated in 8 of the 11 sulforaphane-treated grafts. This result suggests that sulforaphane might be beneficial in the treatment of H. pylori-infected individuals.The recommended treatment of Helicobacter pylori-associated diseases today includes a combination of two or more antibiotics with an inhibitor of acid secretion. However, even with these treatments, some bacteria may persist, in a nongrowing, tolerant form or possibly intracellularly (5,7,10). This may lead to eradication failure, which is defined as the persistence of H. pylori at least 1 month after the end of antimicrobial therapy (9). Moreover, development of resistance of H. pylori strains to one or more of the antibiotics commonly used has been demonstrated previously (28). Thus, a need for new therapeutic agents that are effective against extracellular and potentially intracellular forms of H. pylori exists. We recently showed that sulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli and broccoli sprouts, is a potent bactericidal agent against both extra-and intracellular H. pylori in vitro (11). Substantial quantities of isothiocyanates (up to 100 mg daily) and even greater quantities of their glucosinolate precursors are widely consumed by humans (12,13,29). They may act locally within the gastrointestinal tract or may distribute systemically after conversion to their cognate isothiocyanates (12,15,34). In this study, we investigated the efficacy of sulforaphane in vivo against H. pylori by using a recently developed model which uses human gastric xenografts in nude mice (22).Sulforaphane, i.e., [(Ϫ)-1-isothiocyanato-(4R)-(methylsulfinyl)butane] was kindly provided by J. W. Fahey (Johns Hopkins University School of Medicine, Baltimore, Md.). Stock solutions were prepared in acetonitrile, and further dilutions were made in sterile water. H. pylori strain 26695, which was previously adapted for use in the gastric xenograft model (23), was used for graft inoculation. The strain was grown on Columbia agar supplemented with 10% horse blood under microaerobic conditions as previously described (22). For this isolate, the MIC of sulforaphane was 4 g/ml, as determined by using the agar dilution method (pH 7.4) as recommended by the National Committee for Clinical Laboratory Standard (NCCLS) (30).Xenografts exhibiting human mature gastric epithelium and acidic secretion were obtained in nude mice as previously described (22) and with the approval of the French National Consultative Ethical Committee. Bacterial inoculation was performed by using a catheter that was implanted in the xenograft lumen (22). Two weeks after inoculation, each graft was microsurgically opened. Mucus was sampled for qualitative cult...

Chemoprotection by sulforaphane: Keep one eye beyond Keap1

“…SFN was recently shown to inhibit several strains of H. pylori, including antibiotic-resistant strains, with a minimal inhibitory concentration of 4 μg/ ml [30]. Moreover, SFN administered at 7.5 μmol per day for 5 days eradicated H. pylori from human gastric xenografts in nude mice [33]. The precise mechanism(s) through which SFN protected in these studies remains unknown.…”

Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis

“…Purified SFN inhibited the growth and killed multiple strains of H. pylori in the test tube and in tissue culture, including antibiotic resistant strains [125]. In an animal model of H. pylori infection, SFN administration for 5 days eradicated H. pylori from 8 out of 11 xenografts of human gastric tissue implanted in immune-compromised mice [126]. However, in a small clinical trial, consumption of up to 56 g/d (2 oz/d) of glucoraphanin-rich broccoli sprouts for a week was associated with H. pylori eradication in only 3 out of 9 gastritis patients [127].…”

Biosynthesis and bioactivity of glucosinolates and their production in plant in vitro cultures

“…On the other hand, glucosinolates and isothiocyanates also have antibacterial and antifungal activities. In fact, the allyl isothiocyanate or sulforaphane has antibacterial and antifungal activity against various human pathogens (Ishida et al 2014 and references therein; Fahey et al 2002;Haristoy et al 2003;Vig et al 2009). In addition, sulforaphane has been considered as a potent agent against viruses (Furuya et al 2016).…”