Metabolism of &lt;sup&gt;14&lt;/sup&gt;C-Rhein and &lt;sup&gt;14&lt;/sup&gt;C-Rhein Anthrone in Rats

Witte, Peter de; Lemli, J

doi:10.1159/000138435

Cited by 19 publications

(13 citation statements)

References 3 publications

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“…Senna activity depends on the release, by bacterial enzymes, of active metabolites, rhein and rhein anthrone in the gut lumen [12,13]. Perfusion of rat colon in vitro with either rhein or rhein anthrone did not in crease colonic PAF levels, even when the con centrations used were higher than those com monly present in human intestinal lumen.…”

Section: Discussionmentioning

confidence: 99%

Effect of Senna Is Not Mediated by Platelet-Activating Factor

Capasso

Izzo²,

Mascolo³

et al. 1993

Pharmacology

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The effect of in vivo treatment with senna was examined on the ex vivo formation of platelet-activating factor (PAF) by small and large intestine of rat, mouse and guinea pig. A single or a prolonged oral administration of senna (60-240 mg/kg) to animals did not increase intestinal PAF content. Nor did senna increase the intraluminal release of acid phosphatase. A similar result was obtained in the colonic tissue of rat perfused in vitro with rhein (1-500 μg/ml) or rhein anthrone (1-500 μg/ ml). In contrast, a single oral administration of phenolphthalein (20 mg/kg), bile salts (20 mg/kg) or magnesium sulfate (30 mg/kg) to rats increased intestinal PAF content. Magnesium sulfate also increased the intraluminal release of acid phosphatase. Colonic tissue of rats perfused in vitro with calcium ionophore A23187 (10 μg/ml) formed large amounts of PAF and acid phosphatase. PAF stimulates intestinal motility and secretion and mediates gut damage while acid phosphatase is a marker of cellular damage. Therefore, our data suggest that senna is well tolerated in animals and PAF does not mediate senna-induced laxation.

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Section: Discussionmentioning

confidence: 99%

Effect of Senna Is Not Mediated by Platelet-Activating Factor

Capasso

Izzo²,

Mascolo³

et al. 1993

Pharmacology

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“…In fact it has been shown [28][29][30] that after intracecal administration of phar macologically active amounts of [14C]rhein anthrone to rats, about 88% of the dose was excreted with the produced diarrhea in the first hours. However, 3% of the administered radioactive dose can be recovered in urine in a 5-day period, and therefore has been ab sorbed [28][29][30] (fig. 4).…”

Section: Fate O F Rhein Anthrone After Absorptionmentioning

confidence: 99%

“…However, kidneys revealed a higher retention ability: 8.6 pg/g the first day, de creasing by some 40% over the following 4 days. This affinity for kidney tissue was con firmed by studies with radiolabelled anthraquinones like rhein and emodin [28][29][30][31][32], Since anthraquinones can be reduced to anthrones by the intestinal flora (see further), it is presently not known if, besides the an- throne, also the anthraquinone form is re tained in the kidney.…”

Section: Fate O F Rhein Anthrone After Absorptionmentioning

confidence: 99%

“…A study with rhesus monkeys gave simi lar results [34], Several metabolites in urine were found but the small amount of anthranoids detected in urine hampered their identification. Proba bly several of them were glucuronides and sul phates, as detected in urine of rats after ad ministration of [14C]rhein anthraquinone [28][29][30][31] and [14C]emodin [32], The origin of the conjugates is not known. Of interest, Sund and Elvegard [35] found that anthraquinone undergo an intestinal wall metabolism pro ducing second-phase conjugates.…”

Section: Fate O F Rhein Anthrone After Absorptionmentioning

confidence: 99%

“…This instability of rhein anthrone [14] as well as the antipsoriatic drug dithranol [36] in oxidative circumstances are well docu mented, although the degradation products are still unknown. Probably the reactions are initiated with the formation of an highly reac tive 10-anthranyl radical, which then is grad ually degraded in several oxidation products, including substances with a brown color [14,36], Also a study with [l4C]rhein anthrone ad ministered intracecally to rats [28][29][30] re vealed the same unknown derivatives in ex tracts of feces collected daily. Furthermore, only 36% of the radioactivity present could be extracted.…”

Section: Fate O F Rhein Anthrone In Fecal Extractsmentioning

confidence: 99%

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Metabolism and Pharmacokinetics of Anthranoids

Witte¹

1993

Pharmacology

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Anthranoid derivatives are used all over the world as a treatment for constipation. These compounds are present in several drugs of plant origin, especially as O- or C-glycosides. Besides featuring different substituents, the aglycone might consist of an anthraquinone, an anthrone or a dianthrone. So far, detailed information concerning their metabolism and pharmacokinetic characteristics is available only in a few cases. The best characterized compounds are sennoside, a dianthrone O-glycoside present in senna leaves and senna pods, and its aglycone (rhein anthrone). After oral administration, sennoside is degraded only in the lower parts of the gastrointestinal tract, releasing its active metabolite rhein anthrone. Nowadays, this process is understood at the molecular level. A study with ¹⁴C-labelled rhein anthrone administered intracecally to rats, revealed that the compound is scarcely absorbed. Since on the contrary its anthraquinone equivalent is absorbed to a much larger extent, it is inferred that dianthrone- or anthrone-glycosides exhibit a lower systemic availability than anthraquinone O-glycosides.

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In vitro reduction of rhein anthraquinone to rhein anthrone by rat cecal microflora and some intestinal bacterial strains

Witte

Hoestenberghe

Eyssen

1992

Biopharm & Drug Disp

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After in vitro incubation of cecal content from CVL or gnotobiotic rats with rhein anthraquinone (1 mg g-1) for 18 h at 37 degrees, the anthraquinone was converted to rhein anthrone for 23.5 (SD +/- 3.4) per cent and 19.4 (+/- 4.7) per cent, respectively. Liquid cultures of some strictly anaerobic fecal bacteria of man and mouse incubated with rhein anthraquinone (62.5 micrograms ml-1) for 48 h at 37 degrees, revealed only small amounts of reduced substance. Although the underlying mechanisms of the differences in both conditions remain unclear, the experimental data accentuate the need for using cecal content when exploring the in vitro metabolism of anthranoids by the intestinal microflora. The conversion was chemically proven by derivatization of the anthrone with 4-nitroso-N-N-dimethylaniline in pyridine, followed by hydrolysis and identification of the released anthranoid by mass spectrometry. The in vitro reduction capacity of the cecal content of CVL rats was drastically decreased by oral administration to rats of different combinations of neomycin sulfate, metronidazole, bacitracin and Na-penicillin G. In these cases the conversion ranked between 0.2 per cent and 5.2 per cent the first day after administration. It is concluded that rhein anthraquinone in cecal content is reduced to the highly reactive and labile rhein anthrone, which accounts for the in vivo disappearance of dihydroxy-anthranoid equivalents in routine analysis after oral administration of anthraquinones to experimental animals.

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Metabolism of <sup>14</sup>C-Rhein and <sup>14</sup>C-Rhein Anthrone in Rats

Cited by 19 publications

References 3 publications

Effect of Senna Is Not Mediated by Platelet-Activating Factor

Effect of Senna Is Not Mediated by Platelet-Activating Factor

Metabolism and Pharmacokinetics of Anthranoids

In vitro reduction of rhein anthraquinone to rhein anthrone by rat cecal microflora and some intestinal bacterial strains

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