benzofurans and Spermatic-Cord-Torsion

Topics: Adolescent; Adult; Animals; Benzofurans; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Spermatic Cord Torsion; Testis; Young Adult

Testicular damage after torsion has been attributed to many mechanisms, of which one is lipid peroxidation of the plasma membrane, which could cause the activation of the mitogen-activated protein kinase family. These proteins are of vital importance for signal transduction pathways and 2 of them, extracellular signal-regulated kinase and c-jun N-terminal kinase, participate in the pathogenesis of testicular ischemia. We investigated whether lipid peroxidation may trigger mitogen-activated protein kinase activation in testicular ischemia-reperfusion.. Adult male Sprague-Dawley rats were subjected to 1-hour testicular ischemia, followed by 24 hours of reperfusion. Sham testicular ischemia-reperfusion rats served as controls. Animals were randomized to receive raxofelast, an inhibitor of lipid peroxidation (20 mg/kg intraperitoneally administered 15 minutes before detorsion and 15 minutes after detorsion) or vehicle (1 ml/kg 10% dimethyl sulfoxide/NaCl solution). A group of animals was sacrificed 0, 10, 15, 20, 25 and 30 minutes, and 1, 2 and 3 hours, respectively, after detorsion to evaluate testicular c-jun N-terminal kinase, extracellular signal-regulated kinase and tumor necrosis factor-alpha activation by Western blot analysis, and mRNA expression and conjugated dienes using a spectrophotometer technique. Another group was sacrificed 24 hours after detorsion to evaluate histological alterations.. Testicular ischemia-reperfusion injury caused a significant increase in the conjugated diene levels, extracellular signal-regulated kinase c-jun N-terminal kinase activity and tumor necrosis factor-alpha expression in both testes. Furthermore, histological examination revealed marked damage. Raxofelast inhibited these parameters and decreased histological damage.. These data suggest that lipid peroxidation triggers extracellular signal-regulated kinase and c-jun N-terminal kinase activation. Furthermore, mitogen-activated protein kinase blockade might represent a potential therapeutic approach to treatment in patients with unilateral testicular torsion.

Topics: Animals; Antioxidants; Benzofurans; Extracellular Signal-Regulated MAP Kinases; JNK Mitogen-Activated Protein Kinases; Lipid Peroxidation; Male; Rats; Reperfusion Injury; RNA, Messenger; Spermatic Cord Torsion; Tumor Necrosis Factor-alpha; Vitamin E

Testis torsion is a surgical emergency that lead to permanent gonad damage. The damage has been ascribed to mechanisms of ischemia-reperfusion similar to other tissues. The mechanisms involved are different, but the lipid peroxidation of plasma membrane, caused by reactive oxygen species (ROS), generated particularly during reperfusion, is one of the most accredited. In the present study, we aimed to evaluate the effects of raxofelast, a vitamin E-like antioxidant with potent action and no systemic toxicity, on lipid peroxidation and histopathology in both testes after unilateral testicular torsion and detorsion. Adult male Wistar rats were subjected to total occlusion (3 h) of the left testis followed by 4 hours of reperfusion (TI/R). Sham testicular ischemia-reperfusion rats (SHAM TI/R) were used as controls. The animals were then randomized to receive either vehicle (1 ml/kg/i.p. of a dimetylsulphoxide/NaCl 0.9% 1:10 v/v solution, injected either 15 min before detorsion and 15 min after detorsion) or raxofelast (20 mg/kg i.p. 15 min before detorsion and 15 min after detorsion). Conjugated dienes (CD) levels, an index of lipid peroxidation, and testis histopathology were evaluated. Testicular ischemia reperfusion (TI/R) in untreated rats produced high testicular levels of CD (3.6+/-0.3 DeltaABS/g protein on the left side and 2.5+/-0.2 DeltaABS/g protein on the right side). Furthermore, histological examination revealed marked damage to the testis interstitium with severe haemorrhage and edema. The administration of raxofelast lowered CD levels (2.8+/-0.2 DeltaABS/g protein on the left side and 1.9+/-0.1 DeltaABS/g protein in the right side) and significantly reduced histological damage. These data suggest that the hydrophilic vitamin E-like antioxidants are good candidates for designing a novel therapeutic strategy to halt the oxidative stress that follows acute testis torsion.

Topics: Animals; Antioxidants; Benzofurans; Ischemia; Lipid Peroxidation; Male; Rats; Rats, Wistar; Reperfusion Injury; Spermatic Cord Torsion; Testis; Vitamin E