Curcumin exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT–3/IL–6 signaling pathway in rats

Objective(s): This experiment was carried out to investigate the protective effects of curcumin (CUR) on testicular damage induced by the valproic acid (VPA) administration. Materials and Methods: Male Wistar–Albino rats (n=28, 250–300 g) were randomly divided into four groups: Control (1 ml saline, oral), VPA (500 mg/kg, IP), CUR (200 mg/kg, oral), or VPA+CUR (500 mg/kg, VPA, IP plus 200 mg/kg CUR, oral). The treatments were applied for 14 days. Serum testosterone and testis [Janus kinases1 (JAK1), signal transducers and activators of transcription–3 (STAT–3), interleukin–6 (IL–6), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF–α), interleukin–18 (IL–18), and nuclear factor (NF)–κB)] samples were collected for biochemical analyses. Semen samples were subjected to microscopy for spermatological parameters. Testis tissue was also analyzed for histopathological and immunohistochemical methods. Results: The VPA administration caused a 37% decrease in serum testosterone concentration and 5.32, 9.51, 2.44, and 3.68–fold increases in testicular tissue JAK1, STAT–3, IL–6, and MDA levels, respectively. There were also 50, 52, and 72% reductions in sperm motility, sperm viability, and the mean testicular biopsy score, respectively, accompanied by considerable degenerative changes and necrosis in seminiferous tubules in the VPA group. There is also an immune-positive reaction for IL–18 and NF–κB in only Leydig cells. Conclusion: The CUR treatment may be beneficial in restoring testicular damage through antiinflammatory and anti-oxidant potential.