Cathinone from Khat (Catha edulis) Leaves Induces Testicular Dysfunction in Male Vervet Monkeys through Dose-dependent Regulation of Testicular Steroidogenesis-associated Genes and Hormone Synthesis

Abstract

<title>Abstract</title> <bold>Background</bold> Consumption of fresh khat (<italic>Catha edulis</italic> Forssk.) leaves has been shown to affect reproductive health, especially with regards to impaired male reproductive function. (-)-cathinone, the principal alkaloid in khat plant is known for its euphoric and psychostimulatory effects. Additionally, high dose and chronicity of exposure to khat extract and (-)-cathinone has been associated with impaired reproductive hormone synthesis in experimental animal models. It is currently not known whether the expression of genes encoding for specific testicular enzymes along sex steroid biosynthetic pathway are involved in this impairment. The present study aimed to examine the effects of (-)-cathinone from fresh khat leaves on mRNA expression of steroidogenesis-associated genes (3b hydroxy steroid dehydrogenase [3b-HSD] type I and 17b hydroxy- steroid dehydrogenase [17b-HSD] type I) and intra-testicular hormone production in vervet monkey testis. <bold>Methods</bold> Eight male animals were divided into 4 groups, with treatment subjects being administered (-)-cathinone at 0.8, 3.2 and 6.4 mg/kg body weight, respectively while control group was administered normal saline. The mRNA expression of steroidogenesis-associated genes using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR as well as <italic>ex vivo</italic> studies for measurement of intracellular progesterone, androstenedione and testosterone levels of interstitial cells were investigated. <bold>Results</bold> Results showed that (-)-cathinone at 3.2 and 6.4 mg/kg body weight (medium and high doses, respectively) significantly (<italic>P</italic>&lt; 0.05) increased mRNA expression of 3b-HSD type I and 17b- HSD type I compared to the control group whereas the changes in 3b-HSD type I and 17b- HSD type I expression were not significant for (-)-cathinone at 0.8 mg/kg body weight. There was an increased intra-testicular progesterone, androstenedione and testosterone in cultured interstitial cells exposed to luteinizing hormone but which was significantly suppressed when co-treated with (-)-cathinone at 100 µl of 6.4 mg/kg body weight. <bold>Conclusion</bold> In conclusion, the results demonstrated that (-)-cathinone at high doses has the potential to affect steroidogenesis and thus directly or indirectly influence spermatogenic processes and general reproductive function in the habitual male (-)-cathinone/khat user.