Mitochondrial Uncoupling Activity as a Possible Base for a Laxative and Antipsoriatic Effect

Verhaeren, E. H. C.

doi:10.1159/000137397

Cited by 20 publications

(7 citation statements)

References 16 publications

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“…Figure 5 shows the increase in reduced cytochrome c as a function of time after addition of Frangulaemodinanthrone and the well-known antipsoriatic dithranoL One sees that Frangulaemodinanthrone reduces cytochrome c, while dithranol, a representative anthrone of the second group, has almost no effect Our results show that free 1,8-dihydroxyanthrones and -anthraquinones with an additional phenolic hydroxyl group or an carboxyl group inhibit Na + -K + -ATPase activation by reducing ATP level resulting from an interference with oxidative ATP production, while their corresponding O-and C-glycosyls-like aloins or glucofrangulins-have no influence (Table I). This is in agreement with the results of other authors who have demonstrated inhibition of Na + -K + -ATPase by several anthranoids (14,15). The question still remains open whether this inhibition is sufficient to explain the observed laxative effects.…”

Section: Part 1 Influence On Energy Metabolism: An Approach For Intesupporting

confidence: 93%

Herbal Laxatives: Influence of Anthrones—Anthraquinones on Energy Metabolism and Ion Transport in a Model System

Rauwald¹

1998

ACS Symposium Series

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There is good evidence that anthrones/anthraquinones, known as active metabolites of emodin-type O-and C-glycosyl compounds which are found in many plant laxatives, influence the ion transport across colon cells, although the target transport systems have not yet been elucidated. There are various contradictory results used to explain the laxative action of these drugs. To elucidate this problem we tested 25 different anthrone/anthraquinone metabolites of plant drugs for their influence on different ion transport systems in Ehrlich cells as a model system. Comparing the laxative potency of these substances with their influence on the different ion transport systems involved in trans -epithelial ion transport makes it possible to exclude some transport processes as primary targets of the drugs. The following results were found: (1) Na + -K + -2Cl -cotransport was not inhibited by any of the substances tested. (2) Na + /K + -ATPase (pump) was inhibited by those 1,8-dihydroxyanthrones/anthraquinones that bear an additional phenolic hydroxyl group. This inhibition is indirect by interference with oxidative ATP production. However, there is no correlation to laxative action. (3) Cation channels were not influenced by these drugs. (4) Cl --channels were inhibited significantly by those drugs that also show a laxative action. It is not clear, whether this effect is due to a direct interference with the channels or indirectly due to influences on the signal cascade triggering the transport. These results make it very likely that inhibition of Cl --channels is the primary action responsible for the laxative effect. Interference with oxidative ATP production as an additional effect may explain the known synergistic action described for the combination of different anthrones/anthraquinones or anthranoid drugs, respectively.

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Section: Part 1 Influence On Energy Metabolism: An Approach For Intesupporting

confidence: 93%

Herbal Laxatives: Influence of Anthrones—Anthraquinones on Energy Metabolism and Ion Transport in a Model System

Rauwald¹

1998

ACS Symposium Series

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“…The effect of anthranoids on secretion and absorption is principally induced by a direct interaction between the laxative and the epithelial cells 25 . Anthranoids uncouple mitochondrial oxidative phosphorylation, 26 –28 resulting in a decreased ATP‐production 26 . Lower intracellular concentrations of ATP, combined with a direct inhibition of the Na + /K + ATPase system 15 , 28 –30 on the basolateral membrane of the cell, 31 leads to a breakdown of the ion gradient over the epithelial cell membrane.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Review article: anthranoid laxatives and their potential carcinogenic effects

Gorkom¹,

Vries

Karrenbeld

et al. 1999

Aliment Pharmacol Ther

157

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Anthranoid laxatives are widely used laxatives of natural origin. Because of their chemical structure they are carried unabsorbed to the large bowel, where metabolism to the active aglycones takes place. These aglycones exert their laxative effect by damaging epithelial cells, which leads directly and indirectly to changes in absorption, secretion and motility. Damaged epithelial cells can be found as apoptotic bodies in the pigmented colonic mucosa, characteristic for pseudomelanosis coli. Pseudomelanosis coli is a condition caused by chronic (ab)use of anthranoid laxatives and has recently been associated with an increased risk of colorectal carcinoma. In vitro and animal studies have shown a potential role of anthranoid laxatives in both the initiation and promotion of tumorigenesis. Studies in humans have also suggested tumour promoting activities for these laxatives. Although the short-term use of these substances is generally safe, long-term use cannot be recommended.

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“…There are numerous data suggesting that, corresponding to the morphological changes, the function of the mitochondria is also af fected by dithranol [44,64,[69][70][71]. The ac tivity of nicotinamide adenine dinucleotide (NAD)-dependent isocitrate dehydrogenase (which is found exclusively in mitochondria) is elevated in psoriatic epidermis.…”

Section: Inhibition O F Mitochondrial Respirationmentioning

confidence: 99%

Dithranol: A Review of the Mechanism of Action in the Treatment of Psoriasis vulgaris

Kemény¹,

Ruzicka²,

Braun‐Falco³

1990

Skin Pharmacol Physiol

103

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Dithranol is highly effective in the treatment of psoriasis. The drug inhibits keratinocyte hyperproliferation, granulocyte function and, in addition, may exert an immunosuppressive effect. Free radicals, histamine, eicosanoids and platelet-activating factor have been shown to be involved in dithranol-induced dermatitis, and the oxidation products of the drug are responsible for the staining. Our experimental data suggest that extracellularly generated oxygen free radicals are responsible for both the antipsoriatic and irritative effect of the drug. Furthermore, we could recently provide evidence that extracellularly generated superoxide anion radical also induces an active adaptation mechanism resulting in increased tolerance to dithranol upon repeated application. This adaptive process may explain the requirement for increasing dithranol concentrations to maintain the antipsoriatic efficacy, and also the beneficial effect of other antipsoriatic modalities such as UV-B on dithranol-induced dermatitis. The recognition of this adaptive mechanism may open future prospects to overcome some limitations concerning the practical use of dithranol.

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Mitochondrial Uncoupling Activity as a Possible Base for a Laxative and Antipsoriatic Effect

Cited by 20 publications

References 16 publications

Herbal Laxatives: Influence of Anthrones—Anthraquinones on Energy Metabolism and Ion Transport in a Model System

Herbal Laxatives: Influence of Anthrones—Anthraquinones on Energy Metabolism and Ion Transport in a Model System

Review article: anthranoid laxatives and their potential carcinogenic effects

Dithranol: A Review of the Mechanism of Action in the Treatment of Psoriasis vulgaris

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