Journal Article Ppublish
PubMed: 40850518 DOI: 10.1016/j.reprotox.2025.109038
Eugenol mitigates glyphosate-induced testicular toxicity via modulation of oxidative stress, ER stress, RAGE/NLRP3 and PI3K/AKT signaling pathways in rats.
Reprod Toxicol 137:109038
Authors: Tuba Dogan, Ismail Bolat, Samet Tekin, Burak Cınar, Esra Aktas Senocak, Omercan Alat, Mesut Bünyami Halici
Affiliations
- Department of Biochemistry, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Türkiye.
- Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Türkiye.
- Department of Physiology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Türkiye.
- Department of Pharmacology, Atatürk University Faculty of Medicine, Erzurum, Türkiye.
- Horasan Vocational College, Ataturk University, Erzurum, Türkiye.
- Department of Biochemistry, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Türkiye.
Abstract
Glyphosate (GLY), a widely used herbicide, has been implicated in male reproductive toxicity through mechanisms involving oxidative stress, apoptosis, and disrupted cellular signaling. This study evaluated the protective effects of eugenol (EU), a natural antioxidant, against GLY-induced testicular damage in rats. Thirty-five adult male rats were divided into five groups: Control, EU (100 mg/kg), GLY (150 mg/kg), GLY+EU (50 mg/kg), and GLY+EU (100 mg/kg). Treatments were administered orally for seven days. Testicular tissue was analyzed histologically (H&E staining), and PI3K/AKT signaling was assessed via immunohistochemistry and immunofluorescence. Oxidative stress markers (MDA, GSH, SOD, CAT, GPx) were measured biochemically. Gene expressions related to ER stress, RAGE, and NLRP3 were evaluated by qRT-PCR, while apoptotic (Bax, Bcl-2, Caspase-3), inflammatory (Beclin-1, NF-κB, TNF-α), and antioxidant (Keap1, Nrf2) protein levels were analyzed by western blotting. Co-treatment with EU, especially at 100 mg/kg, significantly ameliorated GLY-induced testicular toxicity by reducing oxidative and ER stress, inhibiting inflammation and apoptosis, and modulating the PI3K/AKT pathway. These findings highlight the potential of eugenol as a protective agent against GLY-induced reproductive toxicity through its regulatory effects on multiple molecular pathways.
MeSH
Stress, Physiological, Eugenol, Oxidative Stress, Antioxidants, Toxicology, Therapeutics, Apoptosis, Rage