Toxicity and antioxidant capacity of Frangula alnus Mill. bark and its active component emodin.

In the present study toxicity of Frangula alnus Mill. bark, widely used as laxative, was investigated. Human peripheral blood lymphocytes (HPBLs) were treated with F. alnus bark extract or emodin (emodin is bark component with laxative property), and cytotoxicity, genotoxicity and parameters of oxidative stress were assessed. Also, polyphenol content of bark extract and antioxidant activity of the extract and emodin measured by DPPH, ABTS and FRAP methods were examined. The bark extract (500 µg/ml) produced cell death and DNA damage, while level of ROS changed at 250 µg/ml. Emodin induced cell death and DNA damage at 150 µg/ml and 200 µg/ml, respectively, and the increase of ROS was observed at 25 µg/ml. These results suggest that both, bark extract and emodin, are cyto/genotoxic to HPBLs and that oxidative stress is involved in the mechanism of their toxicity. The results on antioxidant activity showed that, unlike emodin, bark extract possess moderate antioxidant capacity (44.6%, 46.8% and 2.25 mmol Fe(2+)/g measured by DPPH, ABTS and FRAP assay, respectively) that can be related to relatively high phenolic content (116.07 mg/g). However, due to toxicological properties use of F. alnus bark as well as emodin-containing preparations should be taken with caution.

Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon.

Laxatives abuse has been associated with an increased risk for colon cancer. However, little is known about laxatives long-term carcinogenic potential in experimental studies. The present study was designed to investigate the effects of bisacodyl (4.3 and 43 mg/kg) and cascara (140 and 420 mg/kg) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors. Animals, divided in 10 groups were treated with AOM and laxatives (alone or in combination) for 13 weeks. At the end of treatment animals were killed and the colon removed and analysed for the determination of ACF and tumors. Bisacodyl (4.3 and 43 mg/kg), given alone, did not induce the development of colonic ACF and tumors. Bisacodyl (4.3 mg/kg) coupled with AOM increased the number of crypt per focus, but not the number of tumors. Bisacodyl (43 mg/kg) significantly increased the number of crypt per focus and tumors. Cascara (140 and 420 mg/kg) did not induce the development of colonic ACF and tumors and did not modify the number of AOM-induced ACF and tumors. The results of the present study indicate a possible promoting effect of bisacodyl on rat colon carcinogenesis (especially at higher doses) and absence of any promoting or initiating activity of a laxative and diarrhoeal dose of cascara.

Factores geográficos en la epidemiología de la intoxicación por Karwinskia (tullidora) en México / Geographical factors in the epidemiology of intoxication by Karwinskia (tullidora) in Mexico

Las Parálisis Flácidas causadas por el consumo de los frutos de las plantas del género Karwinskia (tullidora) han emergido como un problema de salud pública en ciertas regiones de México. Investiga los factores geográficos asociados a esta patología, en 72 casos reportados en México de 1990 a 1994. La distribución geográfica de casos coincide con las 11 especies reportadas de Karwinskia en México. La mayoría se relacionaron con la K. humboldtiana y, en menor medida, con K. mollis, K. parvifolia, K. johnstonil y K. rzedowskii. La presencia de casos es mayor en regiones con climas secos (79,2 por cento), vegetación de Matorrales Aridos (41,7 por cento) y altitudes menores de mil metros (54,1 por cento). Se determinaron tres diferentes zonas de riesgo: la zona del río Balsas, la región norte del país, así como las zonas áridas y secas centrales de los estados de Puebla, Hidalgo, San Luis Potosí y Querétaro. Las comunidades menores de 2.500 habitantes y con niveles de bienestar y de educación bajos son las más afectadas.

The role of constitutive and inducible nitric oxide synthase in senna- and cascara-induced diarrhoea in the rat.

The role of constitutive and inducible nitric oxide (NO) synthase in rats treated with senna and cascara was studied. Senna (60 mg/kg p.o.) and cascara (800 mg/kg p.o.) ex vivo significantly increased Ca(2+)-dependent constitutive NO synthase activity in the rat colon. Induction of NO synthase (12% of the total NO synthase) was associated with cascara, but not senna, administration. Dexamethasone (0.03-0.3 mg/kg i.p.), which inhibits the expression of inducible NO synthase, significantly and dose-dependently reduced cascara-(but not senna-) induced diarrhoea and colonic fluid secretion. These findings suggest that senna probably exerts its laxative effect through stimulation of the constitutive isoform of NO synthase, while the inducible isoform of NO synthase also seems to be involved in the laxative effect of cascara.

Evaluation of the potential carcinogenic activity of Senna and Cascara glycosides for the rat colon.

Anthraquinone glycosides of Senna and Cascara were investigated for their ability to induce aberrant crypt foci (ACF) in the rat colon mucosa, which are considered putative preneoplastic lesions. Dietary exposure to high doses of these glycosides for 56 successive days did not cause the appearance of ACF or increase in incidence of ACF induced by 1,2-dimethyl-hydrazine (DMH). However, in rats treated with both DMH and the highest dose of glycosides, the average number of aberrant crypts per focus, considered a consistent predictor of tumor outcome, was higher than in rats given DMH alone. These findings suggest that Senna and Cascara glycoside might behave as weak promoters in rat colon carcinogenesis.

Gastrointestinal toxicity of melos conquer mixture in rats.

GIT effects of Melos Conquer Mixture were investigated - using albino wister rats. Conquer Mixture was administered orally at different concentrations whereas the control group received water. The experiment lasted from 3 to 21 days. Pathological examination was carried out on the dead animals. The animals showed (1) loss of weight and appetite (2) weakness (3) faeces was soft (4) out of 10 animals which received 1.20 ml/kg died on day 5(5) the Glt of the dead rats was virtually empty except in the colon, (6) pieces from various parts of GIT revealed evidence of acute and sub acute inflammatory cellular reactions. The results indicate that Conquer Mixture may be toxic to the gastrointestinal tract and suggest that a re-evaluation of the therapeutic usefulness of the drug in the management of malaria is warranted.