Inhibition of calpain but not caspase protects the testis against injury after experimental testicular torsion of rat.
Testicular torsion requires emergent release of the twisted spermatic cord. Ischemia/reperfusion (I/R) plays an important role in its pathogenesis, and recent data suggest that germ cells undergo apoptosis during I/R. In a model of torsion/detorsion (i.e., I/R) of the rat testis, involvement of calpain and caspase in necrotic and apoptotic cell death was examined. After 1 h of ischemia followed by 0, 0.5, 1, 6, or 24 h of reperfusion, the germ cells positively stained with in situ TUNEL, and DNA fragmentation, activation of caspase-3, and proteolysis of caspase substrates increased with time of reperfusion, demonstrating apoptosis. In addition, m-calpain activation and proteolysis of alpha-fodrin were increased during reperfusion, and its activation is thought to be involved in the necrosis. A calpain inhibitor, acety-leucyl-leucyl-norleucinal, inhibited the phenomena associated with apoptosis and necrosis induced by I/R, although a caspase inhibitor, Z-Val-Ala-Asp-fluoromethlyketone, only inhibited apoptotic changes. The inhibition of calpain but not caspase ameliorated the injury after 60 days of reperfusion following 1 h of ischemia. The calpain inhibitor injected just before reperfusion effectively suppressed alpha-fodrin proteolysis, suggesting its usefulness in the treatment of testicular torsion.
Shiraishi
K
K
Departments of Urology and Legal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Naito
K
K
Yoshida
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002154:Calpain / Q000037:antagonists & inhibitors*; D061945:Caspase Inhibitors; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009336:Necrosis; D009929:Organ Size / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D013086:Spermatic Cord Torsion / Q000188:drug therapy* / Q000473:pathology*; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000473:pathology*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D002154:Calpain