Sevoflurane protects against testicular ischaemia-reperfusion injury in rats

Background and purpose: Testicular torsion, a urological emergency, can lead to testicular dysfunction or infertility due to ischaemia-reperfusion injury, yet current interventions remain limited. Although sevoflurane, an inhaled anaesthetic, has shown organ-protective effects against ischaemia-reperfusion injury in the heart and brain, its role in testicular ischaemia-reperfusion injury is unclear.

Experimental approach: A rat model of acute (720° with 3-h ischaemia/3-h reperfusion) and long-term (720° with 1-h ischaemia/3-day reperfusion) testicular ischaemia-reperfusion injury was set up to explore the protective effects and mechanisms of preconditioning and post-conditioning with sevoflurane.

Key results: 1.5 minimum alveolar concentration (MAC) sevoflurane for 30 min significantly mitigated acute ischaemia-reperfusion injury, as shown by reductions in bilateral testicular oedema, oxidative stress (lower MDA levels), inflammation (decreased TNF-α, IL-6) and Apoptosis (reduced Bax/Bcl-2 ratio). Long-term, it alleviated testicular atrophy and enhanced sperm count, motility and spermatogenesis. Mechanistically, sevoflurane activated ERK1/2 phosphorylation in the RISK pathway, with its protective effects being abolished by the ERK1/2 inhibitor U0126.

Conclusion and implications: Sevoflurane exerts acute and chronic protective effects against bilateral testicular ischaemia-reperfusion injury via ERK1/2 signalling and offers a novel pharmacological strategy to mitigate complications following de-torsion.

ERK1/2; ischaemia–reperfusion; post‐conditioning; pre‐conditioning; sevoflurane; spermatic cord torsion; spermatogenesis; testis.