Multilevel Assessment of Glycemic, Hormonal, and Oxidative Parameters in an Experimental Diabetic Female Rat Model

<b>Background</b>: Diabetes mellitus induces profound metabolic and endocrine alterations, impacting reproductive function through oxidative stress and hormonal imbalances. This study investigated the effects of alloxan-induced diabetes on hormonal status and oxidative stress in female Wistar rats. <b>Methods</b>: A synthetic sulfonamide derivative (compound S) was obtained via chemical synthesis and characterized by elemental and spectral analysis. <i>Salvia officinalis</i> extract was phytochemically profiled using UHPLC-HRMS and assessed for antioxidant potential using DPPH, ABTS, and FRAP assays. The synthetic compound and the plant extract, along with metformin were evaluated in vivo for their potential antihyperglycemic, hormone-regulating, and antioxidant properties., Serum levels of progesterone, estradiol, and follicle-stimulating hormone (FSH) were evaluated alongside oxidative stress biomarkers transforming growth factor-beta 1 (TGF-β1) and glutathione peroxidase 3 (GPX3). <b>Results</b>: Diabetic rats (untreated) exhibited a significant decrease in estradiol (22.00 ± 4.1 pg/mL vs. 54.74 ± 17.5 pg/mL in controls, <i>p</i> < 0.001) and an increase in progesterone levels (17.38 ± 9.6 ng/mL vs. 3.59 ± 0.90 ng/mL in controls, <i>p</i> < 0.05), suggestive for ovarian dysfunction. TGF-β1 levels were elevated in diabetic rats (27.73 ± 19.4 ng/mL vs. 21.55 ± 13.15 ng/mL in controls, <i>p</i> < 0.05), while increased serum GPX3 (61.50 ± 11.3 ng/mL vs. 38.20 ± 12.84 ng/mL in controls, <i>p</i> < 0.05) indicates enhanced oxidative stress. Statistical analysis revealed a correlation between serum GPX3 levels, FSH (<i>p</i> = -0.039), and estradiol (<i>p</i> = -0.025) in the diabetic group (L2). <b>Conclusions</b>: These findings contribute new evidence regarding the effects of diabetes on reproductive hormones and oxidative stress in female models.