Evidence of Regeneration of Testicular and Epididymal Tissue Structure and Function Following Withdrawal from Sub-chronic Khat Exposure: Studies in the Rabbit Animal Model

Abstract

Khat, Catha edulis, use is rampant in Eastern Africa and Middle East countries with associated reports of reproductive function impairment in the body of the user. Reports on recovery post long-term khat exposure are obscure. The present study investigated evidence of restoration of testicular and epididymal structure and function during withdrawal from cytotoxic damage caused by sub-chronic exposure of khat extract. Twenty-eight male rabbits were divided into 7 groups of 4 rabbits each. Group I (control) was administered normal saline while groups II, III and IV were administered 1.0 g/kg, 10 g/kg and 20 g/kg body weight of khat extract, respectively, via oral gavage on alternate days of the week for 12 weeks. Blood samples from animals were collected for hormonal assays followed by euthanasia using 26.4 mg/kg body weight of Sagatal sodium intramuscularly for testicular and epididymal histology. Group V, VI and VII were administered 1.0 g/kg, 10 g/kg and 20 g/kg body weight of khat extract, respectively, orally on alternate days of the week for 12 weeks followed by 1-month withdrawal period, blood samples collected for hormone assays and animals sacrificed for testicular and epididymal histology. High khat dose, 20 g/kg body weight, at sub-chronic exposure caused degeneration in spermatogenic cells with accompanying decrease in plasma FSH and testosterone. Histological output of Sertoli cells, Leydig cells and epididymal epithelium appeared unaffected in treatment groups. Post withdrawal data showed apparent regeneration of seminiferous epithelium and restoration of plasma FSH and testosterone comparable to control. It appears khat extract preferentially affected germ cell spermatogonia and subsequent daughter cells while stem cell spermatogonia were unaffected and contributed to regeneration of germinal epithelium and endocrine function.