The Role of Silymarin in Regulating Cytokine Expression and Antioxidant Status in Testicular Tissue of Hyperglycemic Rats

This study investigated the effects of silymarin (SMN) on hyperglycemia (HPG)‐induced testicular dysfunction, focusing on cytokine expression, antioxidant and endocrine status, and spermatogenesis in a rat model. Rats were divided into three groups: control, HPG‐sole, and SMN‐treated (50 mg/kg orally). Over 58 days, parameters such as Leydig cell steroidogenic activity, sperm count, pro‐inflammatory cytokine levels (interleukin [IL]‐1α, IL‐6, and tumor necrosis factor‐α [TNF‐α]), serum testosterone levels, and testicular antioxidant markers (total antioxidant capacity [TAC], malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], and glutathione reductase [GR]) were assessed. HPG disrupted spermatogenesis, upregulated pro‐inflammatory cytokine expression, reduced Leydig cell activity, suppressed testosterone production, and caused oxidative stress, as evidenced by decreased antioxidant markers and increased MDA levels. SMN treatment significantly improved these outcomes, restoring Leydig cell function, increasing sperm count and testosterone levels, normalizing cytokine expression, and enhancing antioxidant defense (TAC, SOD, CAT, GPx, and GR), while reducing MDA levels. These findings demonstrate that SMN ameliorates HPG‐induced testicular damage by mitigating inflammation and oxidative stress, supporting its potential as a therapeutic agent. SMN’s dual antioxidant and anti‐inflammatory actions underscore its promise in managing infertility associated with HPG‐induced testicular dysfunction, offering a protective strategy to restore testicular health and function.