The Influence of 1′-Methyl- and 1′-Ethylascorbigen on Metabolism of Arachidonic Acid in Murine Spleen Cells

doi:10.1006/bbrc.1993.1133

Biochemical and Biophysical Research Communications

Volume 190, Issue 3, 15 February 1993, Pages 895-900

https://doi.org/10.1006/bbrc.1993.1133 Get rights and content

Abstract

Ascorbigens are indole-containing derivatives of L-ascorbic acid, some or them (e.g., 1′-methylascorbigen) have been shown to inhibit growth or experimental murine tumors. Immunomodulating properties of 1′-methylascorbigen correlated with its antitumor effect. The immunomodulating action of 1′-methyl-ascorbigen is to a marked degree based on its influence on arachidonic acid metabolism in murine spleen cells. A single injection of 50 mg/kg 1′-methylascorbigen leads to pronounced anti immediate increase of the cells′ ability to produce PGE₂ and LTB₄ (up to 550% and 460%, correspondingly). Till the tenth day after injection the levels of these metabolites of arachidonic acid were double that of the control.

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Cited by (4)

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The clastogenic and mutagenic effects of ascorbigen and 1′-methylascorbigen
1994, Mutation Research Letters
Ascorbingen, which occurs naturally in the human diet, and a synthetic analogue (1′-methylascorbigen), were assayed for cytotoxic and clastogenic activities in a SV₄₀-transformed Indian Muntjac cell line (SVM), and for mutagenic activity in the Ames test using Salmonella typhimurium strains TA98 and TA100. Ascorbigen had no effect upon the clonal survival of SVM at concentrations below 0.21 mg/ml and did not induce either chromosome aberrations or sister-chromatid exchanges (SCEs) at any concentration tested up to the maximum compatible with the assay conditions; nor did it induce mutations in either Salmonella strain. In contrast, 1′-methylascorbigen was an order of magnitude more cytotoxic, demonstrating a D_q of 0.03 mg/ml, and whilst it too was not found to induce chromosome aberrations it did induce SCEs in SVM (although only at higly cytotoxic doses) and mutations in the Ames test.
Ascorbigen and other indole-derived compounds from Brassica vegetables and their analogs as anticarcinogenic and immunomodulating agents
1993, Pharmacology and Therapeutics
Searches for the natural compounds that determine the anticarcinogenic properties of a cruciferous-vegetable diet, revealed the products of alkaloid glucobrassicin biotransformations; among these, ascorbigen, an indole-containing derivative of l-ascorbic acid, was found to be the most abundant. Study of chemical properties of ascorbigen showed that it is capable of different transformations in acidic (including gastric juice) and slightly alkaline (including blood) media. The stable and unstable products of ascorbigen transformation determine the biological properties of the compound. The most important product of ascorbigen transformation in gastric juice is 5,11-dihydroindolo[3,2-b]-carbazole, with a binding affinity to the Ah receptor only 3.7 × 10⁻² lower than that of tetrachlorodibenzodioxin. This compound may be responsible for modifying P450 enzyme activities. Ascorbigen and its analogs are available synthetically. Their biological evaluation showed that some of the compounds of these series are immunomodulators. The most active is N-methylascorbigen, which demonstrates therapeutic effects (inhibition of tumor growth, protection of animals from bacterial and viral infections). The immunomodulatory activity of natural ascorbigen may be an additional factor of importance for the anticarcinogenic properties of a cruciferous-vegetable diet.
Indole derivatives in vegetables of the Cruciferae family
2000, Bioorganicheskaya Khimiya

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Regular ArticleThe Influence of 1′-Methyl- and 1′-Ethylascorbigen on Metabolism of Arachidonic Acid in Murine Spleen Cells

Abstract

Regular Article
The Influence of 1′-Methyl- and 1′-Ethylascorbigen on Metabolism of Arachidonic Acid in Murine Spleen Cells