Induction of Rat Hepatic and Intestinal Glutathione S-Transferases and Glutathione by Dietary Naturally-Occurring Anticarcinogens

Nijhoff, W.A.; Groen, Gm; Peters, W.H.M.

doi:10.3892/ijo.3.6.1131

Cited by 42 publications

(35 citation statements)

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“…Significantly, such conjugative metabolism does not seem to include reaction with GSH, thus rendering the possibility unlikely that GSH conjugates of quercetin are causally implicated in its putative nephrotoxic potential. In addition, there is no consistent conclusion to the effect of quercetin on cellular GSH levels by quercetin (Nijhoff et al, 1993, CanivencLavier et al, 1996Sahu and Gray, 1996).…”

Section: Discussionmentioning

confidence: 94%

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

et al. 2004

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Quercetin (3,5,7,3 0 ,4 0 -pentahydroxyflavone) is a flavone with putative ability to prevent cancer and cardiovascular diseases. Its metabolism was evaluated in rats and human. Rats received quercetin via the intravenous (i.v.) route and metabolites were isolated from the plasma, urine and bile. Analysis was by high-performance liquid chromatography and confirmation of species identity was achieved by mass spectrometry. Quercetin and isorhamnetin, the 3 0 -O-methyl analogue, were found in both the plasma and urine. In addition, several polar peaks were characterised as sulphated and glucuronidated conjugates of quercetin and isorhamnetin. Extension of the metabolism studies to a cancer patient who had received quercetin as an i.v. bolus showed that (Quercetin removed) isorhamnetin and quercetin 3 0 -O-sulphate were major plasma metabolites. As a catechol, quercetin can potentially be converted to a quinone and subsequently conjugated with glutathione (GSH). Oxidation of quercetin with mushroom tyrosinase in the presence of GSH furnished GSH conjugates of quercetin, two mono-and one bis-substituted conjugates. However, these species were not found in biomatrices in rats treated with quercetin. As cyclo-oxygenase-2 (COX-2) expression is mechanistically linked to carcinogenesis, we examined whether quercetin and its metabolites can inhibit COX-2 in a human colorectal cancer cell line (HCA-7). Isorhamnetin and its 4 0 -isomer tamarixetin were potent inhibitors, reflected in a 90% decrease in prostaglandin E-2 (PGE-2) levels, a marker of COX-2 activity. Quercetin was less effective, with a 50% decline. Quercetin 3-and 7-O-sulphate had no effect on PGE-2. The results indicate that quercetin may exert its pharmacological effects, at least in part, via its metabolites. Naturally occurring flavonoids in the diet are associated with several beneficial health effects and understanding the mechanisms underlying these effects has become the focus of much research. Quercetin (3,5,7,3 0 ,4 0 -pentahydroxyflavone, for structure see Figure 1) is a prime example of such a flavonoid. Its glycosylated form occurs in kale, French beans, broccoli, apples and especially in onions, with an abundance as high as a quarter to half a gram per kg (Hertog et al, 1992). On ingestion with the diet, quercetin glycosides are rapidly hydrolysed to generate quercetin.Epidemiological evidence links diets rich in quercetin with decreased incidence of cardiovascular and neoplastic diseases

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Section: Discussionmentioning

confidence: 94%

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

et al. 2004

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“…minor non-nutritive constituents of vegetables and fruits which are correlated with decreased cancer risk (6,25,26). From animal studies it has been suggested that these compounds may, at least in part, be effective by virtue of enhancing detoxification systems (6,7,22,26). These detoxi fication enzymes, such as GSTs can reduce carcinogenicity by conjugation reactions with GSH, which is an efficient biochemical mechanism that transforms the carcinogen to a compound with lower biological activity and increased excretability (12,14).…”

Section: Discussionmentioning

confidence: 99%

“…Staining on the immunoblots was quantified using a laser densitometer (Ultrascan; LKB, Bromma, Sweden). Known amounts of purified GST-a, -(.I and -7t were run in parallel with the experimental samples and served as standards for calculation of the absolute amounts of these enzymes (7,21,22). Glutathione was quantised by high performance liquid chromatography after reaction with monobromobi marie as described previously (7).…”

Section: Assaysmentioning

confidence: 99%

“…(iso)thiocyanates and indoles (3). A possible mechanism of action of these constituents may be the induction of gastrointestinal detoxi fication enzymes (4)(5)(6)(7)(8)(9). Important drug metabolizing or detoxi fication enzymes are glutathione S-transferases (GST*; EC 2.5.1.18), a family of isozymes divided into three main classes, a, 7T and ]i (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans

et al. 1995

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A high intake of glucosinolate-containing cruciferous vege tables, such as Brussels sprouts (Brassica oleraceae), has been linked to a decreased cancer risk, but the underlying mechanism is still unclear. The aim of this study was to reveal possible modulating effects of consumption of Brussels sprouts on duodenal, rectal and lymphocytic (i) glutathione S-transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) glutathione (GSH) content. Ten healthy non-smoking volunteers were randomly assigned to two groups in a cross-over design. Five persons started on a glucosinolate-free diet (control period), while the other five consumed 300 g/day cooked Brussels sprouts, at the expense of 300 g glucosinolate-free vegetables (sprouts period). After 7 days the regimen was changed for a further week. At the end of both periods blood samples and duodenal and rectal biopsies were taken. Mean GST activity showed marked differences between duodenal, rectal and lymphocytic cytosols (737 ± 54, 321 ± 29 and 154 ± 14 nmol/min/mg protein respectively), but was uninfluenced by the dietary regimen. Isozyme distribution varied greatly between the tissues. In duodenum GST-a, -7C and -[i iso zymes were expressed in considerable amounts (8441 ± 1365,3002 ± 223 and 536 ± 248 ng/mg protein respectively). Rectal biopsies also contained above three GST classes, but here GST-n was the most pronounced expressed isozyme (2849 ± 246) followed by GST-|n (495 ± 242), while GSTa was only present in minor quantities (149 ± 31). In lymphocytes only GST-71; (755 ± 96) and GST-p, (83 ± 54) could be detected. As a result of the dietary regimen rectal GST-a and -71 levels were slightly increased at the end of the sprouts period, by 30 and 15% respectively. GSH contents were uninfluenced by the dietary regimen. In conclusion, consumption of glucosinolate-containing Brussels sprouts for 1 week results in increased rectal GST-a and -tc isozyme levels. We hypothesize that these enhanced detoxification enzyme levels may partly explain the epidemiological association between a high intake of glucosinolates (cruciferous vegetables) and a decreased risk of colorectal cancer.

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“…Total GSM was quantised by high performance liquid chromatography as described by us recently (17). GSTs class u, j.t and it were quantilied in cytosolic fractions by densilometrie analyses of immunohlois, essentially as described before (12).…”

Section: Tpjmulder Et Aimentioning

confidence: 99%

Glutathione S-transferases and glutathione in human head and neck cancer

Mulder¹,

Manni

Roelofs³

et al. 1995

Carcinogenesis

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Glutathione S-transferase (GST) enzyme activity, GST isoenzyme composition and glutathione (GSH) concentra tion were assessed in normal and squamous cell carcinoma specimens of 14 patients with oral or oropharyngeal cancer and 11 patients with laryngeal cancer. Comparing malig nant with normal oral/oropharyngeal tissues, no significant differences in GSH content, GST enzyme activity or iso enzyme composition were found. However, some tumours had up to 3-fold increased GST enzyme activities and 11 malignant samples over-expressed GST-tc. GST-tc was present in all normal and malignant oral/oropharyngeal specimens investigated, whereas class a and class \i were detected in only a few samples. GST-fj. was present in 28% of the patients with oral/oropharyngeal tumours as compared with -60% in the normal population. GST-a, -|i and -71 were detected in 91, 64 and 100% of the normal laryngeal tissues respectively. In laryngeal tumours signi ficantly higher levels of GST-tc and GSH but signi ficantly lower amounts of GST-a were detected. Levels of class p GST were generally lower in cancerous tissues, but differences were not significant. In comparison with normal oral/oropharyngeal tissues, normal laryngeal tissues con tained almost twice the amount of GST enzyme activity due to higher class a enzyme levels. It is concluded that (ÏST-7C is elevated in 11 out of 14 tumours of the oral cavity and values are significantly increased in tumours of the larynx, which may contribute to the inherent anti-cancer drug resistance of these malignancies. In laryngeal tumours the increased GSH levels may confer additional resistance to radiation therapy.

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Induction of Rat Hepatic and Intestinal Glutathione S-Transferases and Glutathione by Dietary Naturally-Occurring Anticarcinogens

Cited by 42 publications

References 0 publications

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans

Glutathione S-transferases and glutathione in human head and neck cancer

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