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

IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY
Tuba Dogan , Ismail Bolat , Samet Tekin , Burak Cınar , Esra Aktas Senocak , Omercan Alat , Mesut Bünyami Halici
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引用次数: 0

摘要

草甘膦(Glyphosate, GLY)是一种广泛使用的除草剂,通过氧化应激、细胞凋亡和细胞信号中断等机制与男性生殖毒性有关。研究了天然抗氧化剂丁香酚(EU)对gly致大鼠睾丸损伤的保护作用。将35只成年雄性大鼠分为5组:对照组、EU(100 mg/kg)、GLY(150 mg/kg)、GLY+EU(50 mg/kg)和GLY+EU(100 mg/kg)。口服治疗7天。对睾丸组织进行组织学分析(H&;E染色),并通过免疫组织化学和免疫荧光检测PI3K/AKT信号。采用生化法测定氧化应激标志物(MDA、GSH、SOD、CAT、GPx)。qRT-PCR检测内质网应激、RAGE、NLRP3相关基因表达,western blotting检测凋亡(Bax、Bcl-2、Caspase-3)、炎症(Beclin-1、NF-κB、TNF-α)、抗氧化(Keap1、Nrf2)蛋白表达水平。与EU共处理,特别是100 mg/kg,通过降低氧化应激和内质网络应激,抑制炎症和细胞凋亡,以及调节PI3K/AKT通路,显著改善gly诱导的睾丸毒性。这些发现强调了丁香酚通过其多种分子途径的调节作用,作为抗gly诱导的生殖毒性的保护剂的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.
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来源期刊
Reproductive toxicology
Reproductive toxicology 生物-毒理学
CiteScore
6.50
自引率
3.00%
发文量
131
审稿时长
45 days
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.
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