Xanthine oxidase inhibitors suppress testicular germ cell apoptosis induced by experimental cryptorchidism.
Apoptotic degeneration of germ cells in cryptorchid testis is associated with an increased level of reactive oxygen species, and may be prevented by antioxidant treatment. The objective of this study was to investigate whether xanthine oxidase inhibitors could confer such protection. Unilateral cryptorchidism was surgically induced in the immature rats, which were then left untreated or treated with xanthine oxidase inhibitors, and the testes were evaluated 7 days after the operation. In the control group, the weight of the cryptorchid testis was decreased to 47% of that of the contralateral scrotal testis. However, administration of a xanthine oxidase inhibitor allopurinol (> or = 1 mg/kg/day) significantly attenuated weight reduction of the cryptorchid testis (68-77% of the contralateral scrotal testis, P < 0.01 versus control). Another highly specific xanthine oxidase inhibitor, BOF-4272, also attenuated cryptorchidism-induced testis regression. The effects of allopurinol were associated with decreased apoptosis in germ cells as evaluated by in-situ staining of fragmented DNA. In testicular cells cultured at 37 degrees C, either allopurinol or BOF-4272 prevented DNA cleavage characteristic of apoptosis. In conclusion, xanthine oxidase inhibitors can inhibit germ cell apoptosis induced by experimental cryptorchidism, and may be considered for treatment of male infertility associated with heat stress.
Kumagai
Akiko
A
Department of Obstetrics and Gynecology, Akita University School of Medicine, 1-1-1 Hondo, Akita City, 010-0041 Japan.
Kodama
Hideya
H
Kumagai
Jin
J
Fukuda
Jun
J
Kawamura
Kazuhiro
K
Tanikawa
Hideo
H
Sato
Naoki
N
Tanaka
Toshinobu
T
D000493:Allopurinol / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003456:Cryptorchidism / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006358:Hot Temperature; D007248:Infertility, Male / Q000188:drug therapy; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000187:drug effects*; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000502:physiology
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014227:Triazines; C072977:BOF 4272; D000493:Allopurinol; D014969:Xanthine Oxidase