Does a therapeutical dose of ivermectin impairs testicular homeostasis of rats via excessive apoptosis?

Ivermectin is a medication used to treat parasite infestations in humans and in veterinary medicine. Previously we showed that therapeutical doses of ivermectin impaired spermatogenesis and spermiogenesis in adult rats. The present study was proposed to understand the pathophysiological mechanism that triggered these impairments induced by ivermectin. It was a particular objective to study if ivermectin induced excessive apoptosis. Adult rats were treated with a therapeutical dose of ivermectin (subcutaneously). Their testis was evaluated for the expression of caspase-3 (a marker of apoptosis), using immunohistochemistry techniques. Results revealed that ivermectin treatment increased the expression of caspase-3 (labeled seminiferous tubules and strongly labeled tubules), as well as increased the number of tubules that presented labeled cells in the tubular lumen, compared to the data of the control group. In conclusion, a therapeutical dose of ivermectin induced expressive apoptosis in cells of the seminiferous tubules of rats, affecting the testicular natural homeostasis process, which resulted in the spermatogenesis and spermiogenesis impairments previously reported.

Ivermectin prevents stress-induced testicular damage in juvenile rats.

Ivermectin is a popular antiparasitic drug used in veterinary and human medicine. Studies by our group have shown that therapeutic doses of ivermectin induce some brain and behavioral impairments, especially in the reproductive sphere. So far, the studies were focused in adulthood. Considering that juveniles are more susceptible to drugs during developmental stages and both farm/domestic animals and humans have been medicated with ivermectin in youth, it is necessary to evaluate the possible harm effects in youth. The stress variable is also important, as it potentially influences the effects produced by ivermectin. Therefore, the objective of this study was to evaluate morphofunctional and hormonal reproductive aspects of juvenile rats exposed to ivermectin and/or stressed. Prepubertal male rats were treated with 0.2 or 1.0 mg/kg of ivermectin (a therapeutic dose and a higher dose, respectively). Rats were also submitted to a restraint stress session. The testis morphology and histology were analyzed and plasma testosterone levels were measured. The two doses of ivermectin did not induce a biologically relevant effect on testis and testosterone levels of rats. However, restraint stress impaired macroscopic and microscopic morphometric and stereological parameters, as well as the histology of the testis: it increased the relative testis weight, the tubular diameter, the tubular luminal diameter, and the tubular cellular index, and injured the interstitial area. Previous treatment of juvenile rats with ivermectin prevented most of the stress-induced testes injuries. In conclusion, in addition to be a remarkable antiparasitic agent, ivermectin prevented stress-induced testes injuries in juvenile rats.