Rufigallol attenuates splenic damage caused by STZ by targeting oxidative stress, inflammation, and the apoptosis...

Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from impaired insulin secretion, insulin action, or both. It is associated with progressive organ damage, including splenic injury driven by oxidative stress, inflammation, and enhanced apoptosis. We investigated the protective effects of rufigallol against streptozotocin (STZ)-induced splenic damage in diabetic rats. Diabetes was induced in Wistar rats by a single intraperitoneal injection of STZ (50 mg/kg). Diabetic rats received oral rufigallol (10 or 20 mg/kg/day) for 8 weeks. Fasting blood glucose, spleen weight, hematological parameters, oxidative stress markers (MDA, NO, SOD, CAT, and GSH), inflammatory mediators (IL-1β, IL-2, IL-6, IL-4, TNF-α, IFN-γ, and NF-κB), apoptosis-related proteins (Bax, Bcl-2, and caspase-3), and splenic histopathology were evaluated. STZ administration produced persistent hyperglycemia, reduced spleen weight, anemia, leukocytosis, thrombocytopenia, elevated MDA and NO levels, depletion of SOD, CAT, and GSH, increased concentrations of pro-inflammatory cytokines and NF-κB, upregulated Bax and caspase-3 expression, reduced Bcl-2 expression, and marked histopathological alterations in splenic tissue. Rufigallol treatment significantly lowered fasting blood glucose, improved spleen weight and hematological indices, restored antioxidant defenses, reduced lipid peroxidation and nitric oxide production, suppressed inflammatory cytokines and NF-κB activation, decreased Bax and caspase-3 expression while increasing Bcl-2 expression, and markedly improved splenic histological architecture. The protective effects were consistently greater in the 20 mg/kg group than in the 10 mg/kg group. Our findings suggest that rufigallol attenuated STZ-induced splenic injury by reducing oxidative stress, suppressing inflammatory responses, and normalizing apoptotic markers (Bax, Bcl-2, and caspase-3), thereby preserving splenic structure and function in diabetic rats.

The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05047-9.