The effects of oral ketoconazole and griseofulvin on the fertility of male rabbits

Abstract

T o inves tig ate poss ible s ide e ffe cts of ke tocona z ole a nd g ris e ofulvin on fertility of clinica lly healthy male rabbits . Design: Random iz e d controlle d experim e ntal study. Animals : Thirty mature male rabbits . Proce dure s: Ra bbits we re ra ndom ly a lloca te d into thre e e qua l siz e d g roups (10 a nimals ea ch). T he firs t g roup s e rve d as a control g roup (re ceive d no tre atm e nt), the s e cond group re ce ive d g ris e ofulvin (25 mg / kg B.W ) orally for 30 da ys , a nd the third g roup re ce ive d ke tocona z ole (50 mg / kg B.W ) ora lly for 30 da ys . Se m e n sa m ple s we re colle cte d afte r 1 da y, 1 we e k a nd 2 we e ks post -a dm inistra tion to de te rm ine s pe rm m otility, % of live a nd de a d s pe rm s , tota l s pe rm a bnorm a lities a nd s pe rm cell conce ntra tion. T wo we e ks pos t-a dm inis tration, tes tes a nd e pididym ides we re re m ove d for histopa tholog ica l examination. Re s ults: Both drug s produce d a sig nifica nt re duction in the se rum tes tos te rone le ve l, sperm cell concentra tion, percent of live sperms and percent of sperm motility. Conclus ion and clinical re le vance: Ke toconaz ole a nd g ris e ofulvin ha ve a ne ga tive impa ct on fertility of male rabbits , and the effect is more pronounce d with ketoconaz ole .

Study of Plasma Corticosterone Upon Chronic Stress Induction and Its Effect on Follicular Development in Rattus norvegicus

“…But, in the same study, rats with 12 weeks of stress exposure have exhibited 1.56 ± 0.12 ng/mL of testosterone which exhibits a significant elevation compared with the control. In addition to the rats, a similar study using the same dosage of ketoconazole (50 mg/kg body weight) in male rabbits also revealed a considerable drop in testosterone, measuring 0.80 ± 0.24 ng/mL, which is significantly lower when compared to the control [19]. This effect is because of the potential inhibiting effect of ketoconazole on 17, 20-desmolase, which is an enzyme that helps in the production of androgen [16].…”

Reversible infertility in male dog following prolonged treatment of Malassezia dermatitis with ketoconazole

“…Ketoconazole is a potent inhibitor of testosterone synthesis in isolated rat Leydig cells [ 13 ] and in dispersed human, dog and rat testicular cells [ 14 ]. It has been reported that ketoconazole significantly suppressed testosterone concentrations in dogs [ 8 , 15 ], humans [ 13 , 16 ], rats [ 6 ] and rabbits [ 17 ]. Studies in rodents showed that ketoconazole also impairs spermatogenesis, leading to decreased semen quality.…”

“…Orally administered ketoconazole was found in seminal plasma trough 30 h after dosing [ 8 ]. It has been reported that ketoconazole induced degeneration of the seminiferous tubules and arrested spermatogenesis in testes of rats [ 31 ] and rabbits [ 17 ].…”

Effect of drugs on fertility in male dogs: A review

“…Griseofulvin has genotoxic, carcinogenic and teratogenic effects in laboratory animals (Knasmüller et al, 1997). It has been reported to cause oligospermia in rabbits (Mohamed et al, 2020). However, von Heimendahl et al (2004) found no effect of griseofulvin treatment (25 mg/kg per day for 30 days) on semen quality in dogs.…”