Oxidative Stress

Myo-inositol attenuates diabetes-induced testicular injury through Nrf2/Bcl-2 signaling in rats.

Journal of diabetes and metabolic disorders

Abstract

PURPOSE: Insulin resistance from pancreatic beta cell malfunction causes type 2 diabetes mellitus (T2DM), hyperlipidemia, and disrupting the endocrine system. Due to its antioxidant and insulin-mimetic properties, myo-inositol (MI) can enhance insulin sensitivity, thereby reducing oxidative stress and inflammation. This study examined MI 's antiglycemic, antioxidant effects, and potential to reduce insulin resistance, focusing on its impact on serum markers, testicular health and, apoptosis regulation in rats with T2DM. METHODS: The study investigated testicular histology, serum and tissue biochemistry, gene and protein expression, and inflammatory factors in rats with T2DM. RESULTS: MI treatment significantly increased the overall testis volume, including its components, and the average number of spermatogenic and somatic cells, which had decreased in the T2DM group. In the T2DM + MI group, levels of testicular testosterone, superoxide dismutase (SOD), total antioxidant capacity (TAC), nuclear factor erythroid 2-related factor 2 (Nrf2), and Bcl2 gene and protein expression significantly increased, while serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), testicular malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), Interleukin - 6( IL-6), and Bax gene and protein expression decreased compared to the T2DM group. CONCLUSION: MI treatment may counteract diabetes-induced damage to testicular histology and spermatogenesis by reducing oxidative stress, apoptosis, and inflammation through activation of the Nrf2 / Bcl2 pathways.

Key Findings

  • Myo-inositol treatment significantly improved testicular volume and cell counts in diabetic rats.
  • Myo-inositol increased testicular testosterone, antioxidant markers (SOD, TAC), and Nrf2/Bcl2 gene and protein expression.
  • Myo-inositol decreased serum cholesterol, LDL-C, testicular MDA, inflammatory cytokines (TNF-α, IL-6), and pro-apoptotic Bax expression.

Clinical Significance

Myo-inositol may protect against diabetes-induced testicular injury by reducing oxidative stress, inflammation, and apoptosis via activation of the Nrf2/Bcl2 signaling pathway, suggesting potential therapeutic benefits for diabetic reproductive complications.

Citation

Kiani Mina, Mehranjani Malek Soleimani, Shariatzadeh Mohammad Ali. Myo-inositol attenuates diabetes-induced testicular injury through Nrf2/Bcl-2 signaling in rats. Journal of diabetes and metabolic disorders. 2026-Dec.

DOI: 10.1007/s40200-026-02049-5