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.

An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis

“…Failure of metabolic supply, owing to the dimunition of oxygen in ischemia, decreased cellular stores, and accumulation of toxic metabolites lead to germ cell death. 1 Rotation of spermatic cord is initially accompanied by edema attributed to venous and lymphatic obstructions. Advancement of obstruction impedes arterial circulation, which is followed by testicular infarct.…”

“…3 Free-oxygen radicals are linked with ischemia reperfusion (I/R) injury. 1 These free-oxygen radicals exert their deleterious effects by destruction of the structural elements of the cell. Various antioxidants, like vitamin E, allopurinol, and melatonin, have been used to alleviate the hazardous impacts of free-oxygen radicals.…”

Montelukast prevents testes against ischemia-reperfusion injury through suppression of iNOS expression

“…[2] Therefore, many pharmaceutical agents are under investigation that can be used as an adjunct to surgery in order to improve the testicular salvage rates. [3][4][5][6][7][8] Montelukast is a selective antagonist of cysteinyl leukotriene receptor 1 (CystLT1) and an anti-oxidant used as an anti-asthmatic drug in the clinical setting. It has been previously reported in experimental studies that it preserves the kidney and the bladder from ischemia/reperfusion damage.…”

Testicular Torsion Treatment as a Male Reproductive Health Concern

“…The degree of fertility loss following testicular torsion depends on the extent of the ischemia and the subsequent damage to the contralateral testis. Substantial body of growing evidence has suggested that testicular ischemia impairs the blood-testis barrier and exposes the contralateral testis to the potential risk of autoimmunization against its own spermatogenic cells [9].…”

“…Based on this concept, several pharmacological agents as well as surgical interventions have been examined to prevent or reverse ischemia-reperfusion induced fertility problems [5][6][7][8][9][10][11][12].…”