Curcumin mitigates testicular ischemia-reperfusion injury by suppressing NLRP3-mediated pyroptosis

Background: Testicular torsion results in damage by interrupting the blood supply. Nevertheless, the reestablishment of blood flow following testicular detorsion, a process known as testicular ischemia-reperfusion injury (IRI), often leads to further injury. Curcumin is a naturally occurring phenolic compound that has anti-inflammatory and antioxidant implications. It has been demonstrated to confer preventive implications in IRI between different organs. We propose ascertaining curcumin function in testicular IRI.

Methods: We created a mouse model to study testicular torsion/detorsion (T/D) and a germ cell model to study oxygen-glucose deprivation/reperfusion (OGD/R). The evaluation of testicular ischemia damage was conducted using histological staining. Testicular tissues were examined for the presence of Reactive Oxygen Species (ROS) and pyroptosis-linked proteins employing western blot (WB), RT-qPCR, MDA, SOD assay kits, and immunohistochemistry analysis. Cell viability and cytotoxicity were measured via the Cell Counting Kit-8 (CCK-8) and LDH test kits. The amounts of inflammatory proteins were quantified employing ELISA, immunofluorescence, and immunoblotting methods.

Results: We observed that testicular IRI is involved in oxidative stress damage in cells, with an associated elevation in pyroptosis-linked proteins NLRP3 and Caspase-1 (CASP-1) levels. Additionally, there is a rise in the inflammatory cytokines IL-1β and -18 levels. After treating with curcumin, we noted a significant inhibition of Pyroptosis, particularly when the concentration was 20 μmol/L, where the inhibitory effect was most pronounced. Further investigation into the underlying mechanisms revealed that curcumin exerts its preventative implications against testicular IRI by targeting the NLRP3 pathway to suppress IRI-mediated Pyroptosis.

Conclusions: Curcumin mitigates testicular IRI-induced Pyroptosis by modulating the NLRP3 signaling pathway, thereby alleviating cellular and tissue damage.

Curcumin; IRI; NLRP3; Pyroptosis; Testicular.