title: Effect of diclofenac on germ cell apoptosis following testicular ischemia-reperfusion injury in a rat.
abstract: Recent evidence suggests that enhanced cell apoptosis is responsible for germ cell loss following testicular ischemia-reperfusion (IR) injury. A nonsteroidal anti-inflammatory drug diclofenac sodium (Voltaren) is a prostaglandin-synthesis inhibitor, which is widely used in many testicular disorders. The purpose of the present study was to examine the effect of diclofenac (DIC) on germ cell apoptosis in the ischemic and contralateral testes following testicular IR in a rat. Forty rats were divided randomly into four experimental groups of ten rats each: group A (Sham)-Sham operated animals; group B (Sham-DIC)-Sham operated rats that were treated with DIC given subcutaneously at a dose of 10 mg/kg, once daily, 24, 48 and 72 h following operation; group C (IR) underwent 90 min of unilateral testicular IR; group D (IR-DIC)-rats underwent 90 min of unilateral testicular IR and were treated with DIC similarly to group B. Ninety-six hours following operation, the rats were sacrificed and testes were harvested. Johnsen's criteria and the number of germinal cell layers were used to categorize the spermatogenesis. TUNEL assay was used to determine germ cell apoptosis in both the ischemic and contralateral testes. Statistical analysis was performed using the non-parametric Kruskal-Wallis ANOVA test, with P less than 0.05 considered statistically significant. Testicular ischemia in rats led to histological damage in the ipsilateral testis. In the contralateral testis, minimal damage was observed. Germ cell apoptosis in both the ischemic and the contralateral testes increased significantly after IR. Treatment with DIC did not change histologic parameters of spermatogenesis in both the ischemic and contralateral testes, but decreased germ cell apoptosis in both testes following testicular IR. We conclude that testicular ischemia causes an increase in germ cell apoptosis in the contralateral testis. Diclofenac may be beneficial for spermatogenesis following testicular IR by decreasing germ cell apoptosis.
authors.affiliation: Rappaport Faculty of Medicine, Technion, Department of Pediatric Surgery B, Bnai Zion Medical Center, 47 Golomb St., P.O.B. 4940, 31048 Haifa, Israel. olguer@bezeqint.net
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Mogilner
authors.forename: Michael
authors.initials: M
authors.lastname: Lurie
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Coran
authors.forename: Ofer
authors.initials: O
authors.lastname: Nativ
authors.forename: Eitan
authors.initials: E
authors.lastname: Shiloni
authors.forename: Igor
authors.initials: I
authors.lastname: Sukhotnik
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D004008:Diclofenac / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000517:prevention & control; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology*; D013086:Spermatic Cord Torsion / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000098:blood supply / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac