Protective Effects of Trigonella foenum‐graecum Extract Against Lead Toxicity: Integrated Redox, Endocrine, and Spermatogenic Responses

ABSTRACT Lead (Pb) exposure remains an important environmental health concern because of its bioaccumulation and toxicity to multiple organs, including the liver, kidneys, and male reproductive system. This study evaluated the protective effects of a standardized Trigonella foenum‐graecum L . (fenugreek; TFG) seed extract against subchronic lead acetate‐induced toxicity in rats. An integrated experimental design assessed biochemical, oxidative, molecular, endocrine, histopathological, and sperm functional parameters. Animals were assigned to control, TFG extract (50 or 100 mg/kg), lead acetate, and combined lead plus TFG extract groups. Lead exposure caused hepatorenal dysfunction and histopathological injury, accompanied by increased malondialdehyde (MDA), reduced antioxidant defenses, increased nuclear factor kappa B (NF‐κB) protein expression, and reduced nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) protein expression. Lead exposure also decreased circulating follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) concentrations and impaired sperm motility, density, morphology, viability, and testicular architecture. Coadministration of the TFG extract significantly attenuated these alterations, improved biochemical and antioxidant indices, reduced NF‐κB expression, increased Nrf2 and HO‐1 expression, improved gonadotropin concentrations and sperm quality, and ameliorated hepatic and testicular histopathology. For most endpoints, the 100 mg/kg/day dose produced greater numerical improvement than 50 mg/kg/day, although between‐dose differences were not consistently significant. These findings indicate that the chemically characterized fenugreek extract attenuates lead‐induced systemic and reproductive toxicity in this preclinical rat model, with effects associated with improved redox balance, inflammation‐related protein expression, gonadotropin concentrations, and spermatogenic outcomes. Further studies are required before therapeutic or translational conclusions can be drawn.