{"title":"丁香酚通过调节大鼠氧化应激、内质网络应激、RAGE/NLRP3和PI3K/AKT信号通路减轻草甘膦诱导的睾丸毒性","authors":"Tuba Dogan , Ismail Bolat , Samet Tekin , Burak Cınar , Esra Aktas Senocak , Omercan Alat , Mesut Bünyami Halici","doi":"10.1016/j.reprotox.2025.109038","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109038"},"PeriodicalIF":2.8000,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Eugenol mitigates glyphosate-induced testicular toxicity via modulation of oxidative stress, ER stress, RAGE/NLRP3 and PI3K/AKT signaling pathways in rats\",\"authors\":\"Tuba Dogan , Ismail Bolat , Samet Tekin , Burak Cınar , Esra Aktas Senocak , Omercan Alat , Mesut Bünyami Halici\",\"doi\":\"10.1016/j.reprotox.2025.109038\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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.</div></div>\",\"PeriodicalId\":21137,\"journal\":{\"name\":\"Reproductive toxicology\",\"volume\":\"137 \",\"pages\":\"Article 109038\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890623825002096\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"REPRODUCTIVE BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890623825002096","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
Eugenol mitigates glyphosate-induced testicular toxicity via modulation of oxidative stress, ER stress, RAGE/NLRP3 and PI3K/AKT signaling pathways in rats
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.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.