Khat (Catha Edulis) Extract Use and Its Effects Following Withdrawal on Endocrine and Gonadal Function in Male Rabbits

Abstract

Gonadal and endocrine effects following withdrawal from sub-chronic to chronic khat (Catha edulis) use remains scanty. Most literature available, though contradictory, highlights on effects of khat on functional systems of the body including the reproductive system in humans and experimental animals during khat exposure. This information, to a large extent, does not provide insights into the possible recovery of „khat addicts‟ from the vice. The aim of this study was to investigate effects of khat extract during sub-chronic exposure and accompanying effects on reproductive function in male rabbits following withdrawal from use. Fresh leaves and shoots of khat were weighed, crushed with mortar and pestle, and dissolved in distilled water in a conical flask for extraction. The working volume of the stock solution for each dose was obtained by factoring in the body weight of the rabbits. The final volumes were standardised by adding normal saline. Sixteen male rabbits were grouped into four groups of 4 rabbits each. The first group (G1) were controls and administered normal saline while the other three groups (G2, G3 and G4) were administered 1.0 g/kg, 10 g/kg and 20 g/kg body weight of khat extract respectively. The test animals were administered the doses of khat extract via oral gavage on alternate days of the week (Monday, Wednesday and Friday) for 12 weeks. Thereafter two animals from each group were sacrificed for histological evaluation of testis, epididymis and kidney. The remaining 2 animals from each group were taken through the withdrawal period of 4 weeks before sacrifice. Blood samples were collected, processed and plasma stored at -20oC until assayed for FSH and testosterone levels for treatment groups as well as controls. Hormonal data and data on clinical observation for difference in means among groups and over the experimental period were analysed by two- way ANOVA at 95% confidence interval followed by Tukey‟ s multiple comparison for post hoc test. Intergroup analysis was done using paired t test. The relationship between weight and levels of testosterone was done using spearman rank correlation analysis at 5% significance level. Khat extract at low dose increased plasma levels of testosterone and FSH while at high dose and over experimental time significantly suppressed testosterone production but the FSH levels were only slightly reduced. This was reversed during withdrawal period where plasma testosterone and FSH in both controls and treatment groups showed no significant difference in their measurements. Histological data on testis during sub-chronic exposure showed vacuolation in germinal epithelium of moderate and high dose treatment groups over experimental period. The same was observed in the epithelial lining of proximal convoluted tubules of kidney nephrons of high dose treatment groups at sub-chronic exposure. However, histological sections of the epididymis appeared unaffected at all doses of khat extract. Following withdrawal from sub-chronic exposure, testicular, epididymal and kidney histology of all treatment groups appeared to regenerate from cellular damage when compared to controls. These results in rabbits have demonstrated for the first time that structural alterations on reproductive system reported variously in literature on khat addicts are reversible following withdrawal from heavy and long-term use in man.