Rosiglitazone, an Agonist of Peroxisome Proliferator‐activated Receptor‐gamma, Prevents Contralateral Testicular Ischaemia–reperfusion Injury in Prepubertal Rats

Abstract

1. Rosiglitazone plays a positive role in the reparation of ischaemia-reperfusion (I/R) injury in different tissues. Thus, we examined its biochemical and histological effects on the contralateral testes to determine whether exogenous rosiglitazone affords any protection against testicular damage. 2. Forty-eight prepubertal male Wistar-Albino rats were divided into six groups. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction for 5 h in all groups except group I, which was the sham-control group. In group II, bilateral orchiectomy was performed following the torsion period. After detorsion both testes were removed in the fifth hour in group III and on the seventh day in group IV. In group V, one-shot rosiglitazone (4 mg/kg) was administered 40 min before detorsion and both testes were removed following the torsion period. In group VI, rosiglitazone was administered (4 mg/kg) 40 min before detorsion and for 7 days, and then both testes were harvested. The tissue levels of malondialdehyde (MDA) were measured and mean testicular biopsy score (MTBS) and mean seminiferous tubule diameter (MSTD) were examined. Immunoexpression of endothelial nitric oxide synthase (eNOS) in testes tissues was investigated by immunohistochemical studies. 3. In the contralateral testis, the MTBS and MSTD values of group VI were significantly higher than those in group IV. Immunohistochemically, mild eNOS immunostaining was present in the germ cells of the contralateral testes in group IV after I/R. In group VI, intense eNOS immunoreactivity was seen in the contralateral testes. 4. Rosiglitazone reduces contralateral testicular damage formed after unilateral testicular torsion and alleviates the oxidative events.

Methylene Blue Increases Contralateral Testicular Ischaemia–reperfusion Injury After Unilateral Testicular Torsion

“…Several theories have been postulated to explain this phenomenon, including auto‐immunization, subclinical episodes of contralateral testicular torsion, the release of acrosomal enzymes, paired neuroendocrine or vasomotor response during torsion, the presence of an underlying defect in spermatogenesis and the presence of inherent gonadal abnormality 13 . Recently, in agreement with the I/R injury hypothesis and the role of free radicals in the disease process, numerous experimental animal studies have confirmed the efficacy of anti‐oxidants, such as superoxide dismutase, catalase, allopurinol, rosiglitazone and aspirin, in reducing the short‐ and long‐term effects of spermatic cord torsion 5,12,15–19 …”

“…Testicular torsion is a widely studied experimental model. However, the pathogenesis of ipsilateral and contralateral testicular damage after unilateral testicular torsion remains poorly understood 9,13–15 . Several theories have been postulated to explain this phenomenon, including auto‐immunization, subclinical episodes of contralateral testicular torsion, the release of acrosomal enzymes, paired neuroendocrine or vasomotor response during torsion, the presence of an underlying defect in spermatogenesis and the presence of inherent gonadal abnormality 13 .…”

Prostacyclin-induced peroxisome proliferator-activated receptor-α translocation attenuates NF-κB and TNF-α activation after renal ischemia-reperfusion injury

“…Although PPAR-␤ and PPAR-␥ agonists have shown therapeutic effects against I/R injury (1,16), the effects of endogenous PPAR-␣ on conditions associated with I/R injury have not been investigated to date. A recent study of NRK-52E cells examined gentamicin-induced apoptosis, in which PGI 2 production was increased by infecting cells with an adenovirus carrying COX-1 and prostacyclin synthase (15).…”

Medical perspective in testicular ischemia-reperfusion injury

“…Rosiglitazone is the most potent and selective peroxisome proliferator-activated receptor-gamma (PPAR-g) ligand. PPAR-g is a member of the nuclear hormone receptor superfamily involved in a number of physiological processes, including atherosclerosis, inflammation, cancer, infertility and demyelination (110). It has been demonstrated that rosiglitazone prevents cell injury by increasing endothelial NOS expression in the contralateral testicular tissue in a model of tIR (110).…”