RESUMEN
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.
Asunto(s)
Antracenos/metabolismo , Antraquinonas/metabolismo , Ciego/microbiología , Intestinos/microbiología , Animales , Cromatografía Líquida de Alta Presión , Vida Libre de Gérmenes , Técnicas In Vitro , Masculino , Oxidación-Reducción , Ratas , Ratas EndogámicasRESUMEN
The effect of rhein and rhein anthrone on the transit and the transport of water and electrolytes in the large intestine was investigated in germ-free rats. After intracaecal administration, neither of the two compounds was found to accelerate the transit of a colour marker through the large intestine. Both drugs reduced the net absorption of sodium and chloride in the colon and enhanced net potassium secretion. Net water absorption was decreased by rhein and even reversed into net secretion by rhein anthrone. Our results show that the secretagogue activity of the compounds is not sufficient to induce laxation in germ-free rats. Furthermore rhein and rhein anthrone had no laxative properties under our experimental conditions.
Asunto(s)
Antracenos/farmacología , Antraquinonas/farmacología , Agua Corporal/metabolismo , Tránsito Gastrointestinal/efectos de los fármacos , Intestino Grueso/efectos de los fármacos , Animales , Electrólitos/metabolismo , Vida Libre de Gérmenes , Absorción Intestinal/efectos de los fármacos , Intestino Grueso/metabolismo , Masculino , RatasRESUMEN
The present study was undertaken to investigate the involvement of prostaglandins in the secretagogue action, observed after intraduodenal administration of rhein anthrone and rhein in rats. After intraduodenal administration of rhein anthrone (50 mg/kg), the active metabolite of sennosides, a very marked increase of secretion was observed compared to control. The amount of secretion was calculated by dividing the total weight of the small intestine, obtained 30 minutes after administration of the drug, by the total length. The effect seen with rhein (50 mg/kg) is far less pronounced than that with rhein anthrone and is not significant when compared with control. Pretreating the animals with indomethacin (15 mg/kg, p.o., 1 hour in advance) or with ibuprofen (15 mg/kg, p.o., 1 hour in advance) largely prevents the secretagogue effect of rhein anthrone, suggesting that prostaglandins play an important role in the observed pharmacological action. This idea is reinforced by the observation that pretreatment with hydrocortisone (50 mg/kg, p.o., 6 hours in advance) is also able to counteract the effect of rhein anthrone. After administration of rhein anthrone, an almost tenfold increase of the tissue content of prostaglandin E2 was observed. Here again, the results with rhein were far less pronounced. It is concluded that prostaglandins play an important role in the secretagogue action of rhein anthrone.