Effects of chrysin in cadmium-induced testicular toxicity in the rat; role of multi-pathway regulation

Background: Cadmium (Cd) is a strong toxic agent and causes serious damage to testicular tissues. Chrysin (CHR) is a natural flavonoid with many effective properties, especially antioxidant, anti-inflammatory and anti-apoptotic properties. The current study describes new evidence for the ameliorative effects of CHR on oxidative stress, apoptosis, autophagy and inflammation pathways in Cd-induced testicular tissue toxicity. Methods: Thirty-five male Wistar rats were divided into five groups, control, Cd, CHR, Cd + CHR25, and Cd + CHR50. Cd was administered alone at a dose of 25 mg/kg body weight or in combination with CHR 25 mg/kg and CHR 50 mg/kg for 7 days. Cd and CHR were administered orally. Biochemical, molecular, and histological methods were used to investigate inflammation, apoptosis, autophagy, and oxidant pathways in testicular tissue. Results: Cd increased lipid peroxidation, JAK-2/STAT-3 levels, inflammation-related NF-κB, TNF-α, IL-1β, IL-6, COX-2, and iNOS levels, AKT-2, FOXO1, Bax, Apaf-1 and Caspase-3 levels, autophagic Beclin-1, LC3A and LC3B. The Cd also caused a decrease in the activities of antioxidant enzymes and GSH levels, antiapoptotic Bcl-2 levels. CHR, on the other hand, had the opposite effect of all these Cd-induced changes. Conclusions: Overall, the data of this study indicate that testicular damage associated with Cd toxicity could be ameliorated by CHR administration. Graphical abstract: [Figure not available: see fulltext.].