Effect of immunomodulator, fingolimod, on ischemia reperfusion testicular injury in rats: Targeting the role of sphingolipid rheostat (fingolimod on I/R induced testicular injury)

Abstract

Objective: To evaluate the potential role of sphingosine-1-phosphate receptor agonist, fingolimod (FTY-720), in rat I/R induced testicular injury and its possible underlying protective mechanisms.

Experimental protocol: Thirty male albino rats were categorized into three groups, 10 rats each: sham operated control group, Ischemia/Reperfusion (I/R) group: underwent torsion/detorsion procedures of the left testes and FTY720 treated (I/R+FTY720) group: received single FTY720 injection (at a dose of 4 mg/kg i.p) 30 min. before detorsion. At the end of the ischemia and reperfusion period (4 h) left testes were dissected carefully in all rats for histological and biochemical investigations. Testicular malondialdehyde (MDA), testicular antioxidant enzymes and testicular sphingolipids were assessed.

Results: FTY720 treatment of I/R group resulted in significant reduction in I/R induced elevation in testicular GSH-Px, SOD, MDA and total ceramide level, along with significant increase in testicular catalase, sphingomyelin and sphingosine-1-phosphate. Also, FTY720 treatment of I/R group improved severe testicular injury changes in I/R group.

Conclusion: FTY treatment may be used as potential therapeutic treatment for I/R induced testicular injury.

Keywords: Testes; Ischemia; Reperfusion; FTY720; Sphingolipids