Testicular toxicity of nitrofurazone causing germ cell apoptosis in rats

T. Shoda et al., Testicular toxicity of nitrofurazone causing germ cell apoptosis in rats, ARCH TOXIC, 75(5), 2001, pp. 297-305
Citations number
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ISSN journal
0340-5761 → ACNP
Year of publication
297 - 305
SICI code
In order to clarify the mechanism underlying testicular toxicity of nitrofu razone (NF), two experiments were performed. In experiment 1, sequential hi stopathological examination of testes after a single oral administration of 100 or 300 mg/kg NF to male rats demonstrated that degeneration of pachyte ne spermatocytes with an eosinophilic, shrunken appearance in stages VII-VI II and vacuolation of Sertoli cells were first observed 12 h after treatmen t. By 24 h, degeneration of pachytene spermatocytes in stages VII-XII and d iplotene spermatocytes were observed. On post-treatment day 4, neither sper matocytes nor spermatids located inside the pachytene spermatocytes in stag e VII were seen anywhere. Generation of seminiferous epithelium progressed with recovery to almost normal morphology after 12 weeks, although some mor phological changes were still present. No lesions were apparent in spermato gonia, preleptotene spermatocytes, leptotene spermatocytes, zygotene sperma tocytes or Leydig cells. Degenerate pachytene spermatocytes and some round spermatids seen after 24 h showed positive TdT-mediated dUTP-biotin nick en d labeling (TUNEL). In addition, DNA laddering patterns were detected with agarose gel electrophoresis, and increased electron density of nuclei and c ytoplasm of degenerating spermatocytes with nuclear chromatin focal aggrega tions were observed by electron microscopy, indicating that cell death was attributable to apoptosis. In experiment 2, sequential serum sex-related ho rmone levels were assayed after a single oral administration of 300 mg/kg N F to male rats and revealed a significant increase of testosterone and a de crease of progesterone at 6 h, and decreases of luteinizing hormone at 12 h and testosterone at 24 h. Prolactin tended to decrease from 12 h after tre atment and the decrease was significant at 48 h. No significant changes wer e observed in levels of follicle-stimulating hormone or estradiol. The prob ability that NF damages germ cells by causing a hormonal imbalance is extre mely low, since no pattern of hormonal imbalance that could be regarded as the cause of the testicular degeneration was observed until 12 h after NF t reatment when pachytene spermatocytes began to degenerate. The present expe riments suggest that NF damages Sertoli cells and pachytene spermatocytes i n stages VII-XII directly.