In vivo production and enzyme-inducing activity of indolo[3,2-b]carbazole

Kwon, Chong Suk; Grose, Karl R.; Riby, Jacques; Chen, Yue Hwa; Bjeldanes, Leonard F.

doi:10.1021/jf00047a030

Cited by 27 publications

(22 citation statements)

References 12 publications

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“…It has been shown in vitro to bind with high affinity to the Ah receptor (37) and transcriptionally activate the CYP1A1 gene (38). Taking into account the variation in I3C dosage between studies, the levels of ICZ in the liver reported in this study are higher than those reported previously (18,39). However, neither of these groups fully validated their analytical method, and without taking factors such as extraction efficiency into account, it is difficult to assess absolute concentrations.…”

Section: Discussioncontrasting

confidence: 73%

Pharmacokinetics and Tissue Disposition of Indole-3-carbinol and Its Acid Condensation Products after Oral Administration to Mice

Anderton

Manson²,

Verschoyle³

et al. 2004

Clinical Cancer Research

196

172

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Indole-3-carbinol (I3C) and 3,3-diindolylmethane (DIM) are promising cancer chemopreventive agents in rodent models, but there is a paucity of data on their pharmacokinetics and tissue disposition. The disposition of I3C and its acid condensation products, DIM, [2-(indol-3-ylmethyl)-indol-3-yl]indol-3-ylmethane (LTr 1 ), indolo[3,2b]carbazole (ICZ) and 1-(3-hydroxymethyl)-indolyl-3-indolylmethane (HI-IM) was studied, after oral administration of I3C (250 mg/kg) to female CD-1 mice. Blood, liver, kidney, lung, heart, and brain were collected between 0.25 and 24 h after administration and the plasma and tissue concentrations of I3C and its derivatives determined by high-performance liquid chromotography. I3C was rapidly absorbed, distributed, and eliminated from plasma and tissues, falling below the limit of detection by 1 h. Highest concentrations of I3C were detected in the liver where levels were approximately 6-fold higher than those in the plasma. Levels of DIM, LTr 1 , and HI-IM were much lower, although they persisted in plasma and tissues for considerably longer. DIM and HI-IM were still present in the liver 24 h after I3C administration. Tissue levels of DIM and LTr 1 were found to be in equilibrium with plasma at almost every time point measured. In addition to acid condensation products of I3C, a major oxidative metabolite (indole-3-carboxylic acid) and a minor oxidative metabolite (indole-3-carboxaldehyde) were detected in plasma of mice after oral administration of I3C. ICZ was also tentatively identified in the liver of these mice. This study shows for the first time that, after oral administration to mice, I3C, in addition to its acid condensation products, is absorbed from the gut and distributed systemically into a number of well-perfused tissues, thus allowing the possibility for some pharmacological activity of the parent compound in vivo.

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Section: Discussioncontrasting

confidence: 73%

Pharmacokinetics and Tissue Disposition of Indole-3-carbinol and Its Acid Condensation Products after Oral Administration to Mice

Anderton

Manson²,

Verschoyle³

et al. 2004

Clinical Cancer Research

196

172

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“…Microbial metabolism of I3C may contribute to endogenous formation of AHR ligands, and could impact the observed physiological effects of dietary broccoli by increasing AHR ligand bioavailability in the distal colon (Kwon 1994). To address this hypothesis, we performed parallel dietary feeding studies in which conventional and germ-free C57BL6/J mice were fed a purified diet with or without supplementation of I3C (125 mg/kg) for seven days.…”

Section: Resultsmentioning

confidence: 99%

Dietary broccoli impacts microbial community structure and attenuates chemically induced colitis in mice in an Ah receptor dependent manner

Hubbard

Murray

Nichols

et al. 2017

Journal of Functional Foods

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Consumption of broccoli mediates numerous chemo-protective benefits through the intake of phytochemicals, some of which modulate aryl hydrocarbon receptor (AHR) activity. Whether AHR activation is a critical aspect of the therapeutic potential of dietary broccoli is not known. Here we administered isocaloric diets, with or without supplementation of whole broccoli (15% w/w), to congenic mice expressing the high-affinity Ahrb/b or low-affinity Ahrd/d alleles, for 24 days and examined the effects on AHR activity, intestinal microbial community structure, inflammatory status, and response to chemically induced colitis. Cecal microbial community structure and metabolic potential were segregated according to host dietary and AHR status. Dietary broccoli associated with heightened intestinal AHR activity, decreased microbial abundance of the family Erysipelotrichaceae, and attenuation of colitis. In summary, broccoli consumption elicited an enhanced response in ligand-sensitive Ahrb/b mice, demonstrating that in part the beneficial aspects of dietary broccoli upon intestinal health are associated with heightened AHR activity.

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“…(248). I3C is a product of glucobrassicin catabolism, a natural ingredient of the above-mentioned foods (188,336).…”

Section: Malassezia-produced Ahr Ligands and Significance Of Ahr Actimentioning

confidence: 99%

The Malassezia Genus in Skin and Systemic Diseases

et al. 2012

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SUMMARY In the last 15 years, the genus Malassezia has been a topic of intense basic research on taxonomy, physiology, biochemistry, ecology, immunology, and metabolomics. Currently, the genus encompasses 14 species. The 1996 revision of the genus resulted in seven accepted taxa: M. furfur , M. pachydermatis , M. sympodialis , M. globosa , M. obtusa , M. restricta , and M. slooffiae. In the last decade, seven new taxa isolated from healthy and lesional human and animal skin have been accepted: M. dermatis , M. japonica , M. yamatoensis , M. nana , M. caprae , M. equina , and M. cuniculi. However, forthcoming multidisciplinary research is expected to show the etiopathological relationships between these new species and skin diseases. Hitherto, basic and clinical research has established etiological links between Malassezia yeasts, pityriasis versicolor, and sepsis of neonates and immunocompromised individuals. Their role in aggravating seborrheic dermatitis, dandruff, folliculitis, and onychomycosis, though often supported by histopathological evidence and favorable antifungal therapeutic outcomes, remains under investigation. A close association between skin and Malassezia IgE binding allergens in atopic eczema has been shown, while laboratory data support a role in psoriasis exacerbations. Finally, metabolomic research resulted in the proposal of a hypothesis on the contribution of Malassezia -synthesized aryl hydrocarbon receptor (AhR) ligands to basal cell carcinoma through UV radiation-induced carcinogenesis.

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In vivo production and enzyme-inducing activity of indolo[3,2-b]carbazole

Cited by 27 publications

References 12 publications

Pharmacokinetics and Tissue Disposition of Indole-3-carbinol and Its Acid Condensation Products after Oral Administration to Mice

Pharmacokinetics and Tissue Disposition of Indole-3-carbinol and Its Acid Condensation Products after Oral Administration to Mice

Dietary broccoli impacts microbial community structure and attenuates chemically induced colitis in mice in an Ah receptor dependent manner

The Malassezia Genus in Skin and Systemic Diseases

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