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PubMed2005

Chemopreventive functions of isothiocyanates.

Numerous animal and epidemiological studies have demonstrated that consumption of cruciferous vegetables is inversely correlated with the cancer incidence. Strong anticarcinogenic activities of cruciferous vegetables are attributed to the high abundance of glucosinolates. Upon consumption, glucosinolates are hydrolyzed into iso-thiocyanates (ITCs), which in turn are conjugated with intracellular glutathione and excreted via mercapturic acid pathway. On the basis of the principle that ITCs can interact with 1,2-benzenedithiole to produce 1,3-benzodithiole-2-thione, a simple high-pressure liquid chromatography-based assay (namely cyclocondensation assay) has been devised to carry out the accurate measurement of the intracellular ITC accumulation. This assay has been adopted to assess the pharmacokinetic profiles of ITCs in humans, to evaluate the enzymatic efficiency of glucosinolate breakdown by myrosinase and to investigate the intracellular absorption and elimination mechanisms of ITCs. In addition, LC-MS-MS has recently been introduced as an alternative quantitative method for ITCs and proved to be superior to cyclocondensation assay, in terms of sensitivity as well as selectivity. Among several possible cellular mechanisms, both the modulation of nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1) and the induction of phase II cellular detoxification and antioxidant enzymes (in brief phase II enzymes) have been proposed as potential molecular mechanisms of chemoprevention by ITCs. In the present review, we describe how ITCs modulate the activity of NF-kappaB and AP-1 and discuss how Nrf2/ARE module was discovered as the central core in the transcriptional regulation of phase II cellular detoxification and antioxidant enzymes.

Animals↗
PubMed2004

Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts.

Intratracheal injection of FITC results in acute lung injury and progresses to fibrosis by day 21 postchallenge. In response to FITC, BALB/c mice produce IL-4 and IL-13 in the lung. To investigate whether IL-4 and/or IL-13 were important profibrotic mediators in this model, we examined the fibrotic response to FITC in mice that were genetically deficient in IL-4 (IL-4(-/-)), IL-13 (IL-13(-/-)), or IL-4 and IL-13 combined (IL-4/13(-/-)). Baseline levels of collagen were similar in all mice. In response to FITC, both BALB/c and IL-4(-/-) mice developed fibrosis, whereas the IL-13(-/-) and IL-4/13(-/-) mice were significantly protected, as measured by total lung collagen levels and histology. Total leukocyte recruitment to the lung was similar in all four strains of mice when measured on days 7, 14, and 21 post-FITC. BALB/c mice showed prominent eosinophilia on day 7 that was absent in IL-4(-/-), IL-13(-/-), and IL-4/13(-/-) mice, suggesting that eosinophilia is not necessary for development of a fibrotic response. There were no significant differences in the percentages of any other leukocytes analyzed between the genotypes. Similarly, protection in IL-13(-/-) mice was not associated with alterations in cytokine or eicosanoid profiles. Interestingly, TGF-beta1 production was not reduced in IL-13(-/-) mice. Analyses of fibroblasts isolated from the four genotypes demonstrated that although there were similar numbers of fibroblasts present in cultures of lung minces, fibroblasts from IL-13-deficient strains have reduced basal and stimulated levels of collagen production. IL-13Ralpha1 expression increases on fibroblasts during fibrotic responses in vivo, and IL-13 increases collagen synthesis in fibroblasts. Thus, IL-13 mediates its profibrotic actions through direct effects on fibroblast production of extracellular matrix.

Animals↗
PubMed2002

[Experience of biologically active supplements to food containing indoles and isothiocyanates in patients with chronic viral hepatitis].

We have studied the effect of dietary supplement "ExPress" on clinical and biochemical parameters and on the activity of detoxification enzymes of liver in patients with chronic viral hepatitis B and C. 24 patients (19 females and 5 males aged 16-39 years) were enrolled in the study. Patients in case group received dietary supplement "ExPress" in addition to basic treatment. Average indices of total bilirubin in cases after treatment were 26.98 +/- 2.85 mmol/l, while in controls--34.31 +/- 5.72 mmol/l (p > 0.05). Average indices of alanin-aminotransferase and aspartate-aminotransferase were 78.75 +/- 11.25 and 160.75 +/- 23.67 units while in controls--208.5 +/- 56.4 and 330.25 +/- 65.14 units respectively (p < 0.05). In case group we observed full normalization of thymol test--from 9.99 +/- 1.51 to 4.03 +/- 0.73 units (p = 0.001), while in controls--from 7.9 +/- 1.56 only to 5.2 +/- 1.15 units (p = 0.194). Contents of non-metabolized antipyrine in cases decreased from 9.76 +/- 1.2% (p = 0.0002) whilst in controls--from 9.38 +/- 1.28% only to 3.93 +/- 1.18% (p = 0.01). Results of the study show that dietary supplement "ExPress" induces the activity of detoxification enzymes of liver and increases the efficiency of basic treatment.

Adolescent↗