Gastrointestinal Effects of Crude Khat (Catha Edulis F) Extract Following Acute and Sub-Chronic Administration in Rodents
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Date
2011-08
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Addis Ababa University
Abstract
Khat (Catha edulis F) belongs to the Celastraceae family and is a dicotyledonous evergreen shrub/tree used for recreation and alleviation of fatigue in several countries of East Africa and South Arabia. Recently, this habit has spread considerably, raising concern in view of medical and socio-economic consequences of khat consumption. Even though khat has several medicinal, social, and economical values, there are numerous reports regarding its gastrointestinal tract (GIT) adverse effects. As the effects of khat chewing on digestive system mentioned in earlier studies were based on clinical observations, the present study was designed to evaluate the GIT activity of the crude khat extract after acute and sub-chronic administration using different rodent models and parameters used for ulcer and motility measurement were quantified. For acute study, animals were randomly assigned into different groups. Negative control received Tween 80 2% in distilled water, whereas positive controls were given ranitidine (pylorus ligation and cysteamine HCl models), misoprostol (indomethacin induced gastric ulcer), and loperamide (castor oil induced diarrhea and enteropooling assay). The other group received different doses of crude khat extract: 100 mg/kg, 200 mg/kg and 300 mg/kg. For sub-chronic study, one group was administered vehicle and served as control, whilst the other three were administered three doses of khat extract (100, 200, and 300 mg/kg) for 45 days.
Acute khat administration in pylorus ligation model was shown to aggravate ulcer compared to controls in the highest dose used, as evidenced by increased volume of gastric acid secretion (p<0.05), total acidity (p<0.05) and ulcer index (p<0.01). Similar results were obtained in indomethacin induced gastric ulcer model where 300 mg/kg khat extract increased mucosal damage as demonstrated by a significant reduction in mucin content compared with misoprostol (p<0.001) and vehicle (p<0.05) treated animals. Khat at 300 mg/kg was also shown to accentuate duodenal ulcer induced by cysteamine HCl by significantly increasing (p<0.01) ulcer area as compared to vehicle-treated rats. Whilst ranitidine was shown to offer antiulcer activity in the models tested, khat at 100 mg/kg was devoid of any significant ameliorating or accentuating effect. Surprisingly, sub-
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chronic administration of khat at all doses failed to produce neither gastric nor duodenal ulcer. In castor oil induced diarrhea, 300 mg/kg (p<0.001) and 100 mg/kg (p<0.01) khat extracts significantly decreased the number of watery fecal discharge against vehicle treated rats. In addition, 300 mg/kg dose decreased (p<0.05) weight and volume of intestinal content in castor oil induced enteropooling model. In sub-chronic studies, 300 mg/kg and 200 mg/kg khat extracts significantly inhibited intestinal motility in in-vivo gastrointestinal motility model by 53.2% and 48.6%, respectively. On the other hand, weight change on sub-chronic khat extract administration was observed and the change became significant at the 3rd (p<0.05), 4th and 5th week (p<0.01), and 6th week (p<0.001) with 300 mg/kg dose. While in 200 mg/kg decline of weight at 4th week (p<0.05) and for following weeks (p<0.01) was obtained. In conclusion, acute use of khat at higher dose in the presence of ulcerogenic agents could aggravate gastric and duodenal ulcer, while sub-chronic khat administration alone did not produce ulcer. Furthermore, acute and sub-chronic administration of khat extract at higher dose produced a significant constipating activity. And sub-chronic administration of khat extract at higher dose markedly decreased body weight. These effects collectively indicate that khat consumption in large amount and for a longer period of time is associated with adverse GIT outcomes. Key words: Catha edulis, Pylorus ligation, Cysteamine HCl, Indomethacin, Castor oil, and Mucin.
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Catha edulis; Pylorus ligation; Cysteamine HCl; Indomethacin; Castor oil and Mucin