Effects of Silver Nanoparticle‐Loaded 18β‐Glycyrrhetinic Acid on P2X7 Receptor and Endoplasmic Reticulum Stress‐Mediated NLRP3 Inflammasome Activation in Testicular Tissue in an Animal Diabetes Model

Diabetes, a metabolic disease characterized by high blood sugar, causes damage to many organs in the body. Accordingly, the present study investigates the effects of silver nanoparticle-loaded 18β-glycyrrhetinic acid (AgNP+18β-GA) on P2X7 receptor and ER stress-mediated NLRP3 inflammasome activation in testicular tissue. 42 Wistar-Albino rats aged 6 months were used. The rats were divided into the following seven groups: Control, AgNP+18β-GA100, DM, DM-18β-GA100, DM-AgNP+18β-GA50, DM-AgNP+18β-GA100, and DM-AgNP. After the experiment, sperm samples obtained from the rats were evaluated. Oxidative stress markers, serum IL-1β, and TNF-α levels were determined in the testicular tissue samples taken separately. In addition, Caspase-1, NLRP3, P2X7, Caspase-3, NF-κB, IRE1, ATF6, and CHOP protein expression levels were evaluated using Western blot analysis of histopathological examinations. Specifically, the most significant decrease was observed in NLRP3, Caspase-1, P2X7, and NF-κB levels in the DM-AgNP+18β-GA100 group (<i>p</i> < 0.05). About sperm parameters, while sperm motility and viability significantly decreased in diabetic groups (<i>p</i> < 0.05), a significant improvement in these values was observed in the AgNP+18β-GA applied groups (<i>p</i> < 0.05). AgNP+18β-GA improved sperm morphology and histopathological damage in diabetes-induced testicular damage, as well as inhibited P2X7 receptor and endoplasmic reticulum stress-mediated NLRP3 inflammasome activation.