Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 19). Effects of two-week repeated dosing of enoxacin on the male reproductive organs.
The toxicity of Enoxacin (ENX), a fluoroquinolone antibacterial agent, on the testis and epididymis was studied in rats. ENX was administered to 5 male rats orally once daily for 2 weeks at the dose level of 3000 mg/kg/day. ENX-treated rats showed a marked decrease in body weight, and two of them died on Day 10. At the end of the dosing period, absolute weights of the epididymis were decreased; in contrast, relative weights of testis were increased in the ENX-treated group. On histopathological examination, testis of ENX-treated rats exhibited the following regressive changes: degeneration of spermatids and spermatocytes, retention of Step 19 spermatids, chromatin margination in nuclei of spermatids, multinucleated giant cell formation, and/or vacuolar degeneration of Sertoli cells. Additionally, desquamated cell debris was observed in the epididymis. Degenerative spermatids and spermatocytes were strongly positive by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). From these results, it is concluded that a 2-week treatment is sufficient to detect toxic effects of ENX on reproductive organs in male rats, and that testicular toxicity induced by ENX is associated with germ cell apoptosis.
Kizawa
K
K
Drug Safety Research Laboratory, Toyama Chemical Co., Ltd., 2-4-1 Shimookui, Toyama 930-8508, Japan.
Furubo
S
S
Sanzen
T
T
Kawamura
Y
Y
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015365:Enoxacin / Q000008:administration & dosage / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008136:Longevity / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D018675:Toxicity Tests
D000890:Anti-Infective Agents; D015365:Enoxacin