Senay Topsakal, Ozlem Ozmen, Kadriye Nilay Ozcan, Halil Asci, Orhan Berk Imeci, Mehmet Abdulkadir Sevuk, Pinar Aslan Kosar
{"title":"氟伏沙明通过改善CD-MPR、KISS-1、AQP4和Claudin-1的表达,抑制NLRP3和NF-κB炎症通路,维持生殖功能。","authors":"Senay Topsakal, Ozlem Ozmen, Kadriye Nilay Ozcan, Halil Asci, Orhan Berk Imeci, Mehmet Abdulkadir Sevuk, Pinar Aslan Kosar","doi":"10.1111/bcpt.70000","DOIUrl":null,"url":null,"abstract":"<p>Fluvoxamine (FLV), a selective serotonin reuptake inhibitor, is commonly used to treat anxiety, major depressive disorder and obsessive-compulsive disorder, among other psychiatric conditions. This study aims to evaluate the effectiveness of FLV in mitigating damage caused by lipopolysaccharide (LPS) to the female genital tract. Thirty-two female Wistar Albino rats were randomly divided into four groups: control, LPS, LPS-FLV and FLV. At the end of the experimental period, tissues from the ovaries, fallopian tubes and uterus were collected for histological, immunohistochemical and genetic analyses. Histological examination of the LPS group revealed mild to moderate bleeding, oedema and neutrophil infiltration. Additionally, there were signs of endometrial damage in the uterus and loss of cilia in the fallopian tubes. Immunohistochemical analysis showed that LPS increased the expressions of nuclear factor kappa beta (NF-κB) and cation-dependent mannose 6-phosphate receptors (CD-MPR) and reduced kisspeptin-1 (KISS-1) expression. Genetic analysis indicated that LPS increased the expression of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) and aquaporin4 (AQP4) genes while decreasing Claudin-1 expression. However, all these adverse effects were reversed by FLV treatment. The study's findings suggest that FLV may be beneficial in treating LPS-induced damage to the female reproductive system.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 3","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786297/pdf/","citationCount":"0","resultStr":"{\"title\":\"Fluvoxamine Inhibited NLRP3 and NF-κB Inflammatory Pathways and Maintained Genital Functions by Ameliorating CD-MPR, KISS-1, AQP4 and Claudin-1 Expressions\",\"authors\":\"Senay Topsakal, Ozlem Ozmen, Kadriye Nilay Ozcan, Halil Asci, Orhan Berk Imeci, Mehmet Abdulkadir Sevuk, Pinar Aslan Kosar\",\"doi\":\"10.1111/bcpt.70000\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Fluvoxamine (FLV), a selective serotonin reuptake inhibitor, is commonly used to treat anxiety, major depressive disorder and obsessive-compulsive disorder, among other psychiatric conditions. This study aims to evaluate the effectiveness of FLV in mitigating damage caused by lipopolysaccharide (LPS) to the female genital tract. Thirty-two female Wistar Albino rats were randomly divided into four groups: control, LPS, LPS-FLV and FLV. At the end of the experimental period, tissues from the ovaries, fallopian tubes and uterus were collected for histological, immunohistochemical and genetic analyses. Histological examination of the LPS group revealed mild to moderate bleeding, oedema and neutrophil infiltration. Additionally, there were signs of endometrial damage in the uterus and loss of cilia in the fallopian tubes. Immunohistochemical analysis showed that LPS increased the expressions of nuclear factor kappa beta (NF-κB) and cation-dependent mannose 6-phosphate receptors (CD-MPR) and reduced kisspeptin-1 (KISS-1) expression. Genetic analysis indicated that LPS increased the expression of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) and aquaporin4 (AQP4) genes while decreasing Claudin-1 expression. However, all these adverse effects were reversed by FLV treatment. The study's findings suggest that FLV may be beneficial in treating LPS-induced damage to the female reproductive system.</p>\",\"PeriodicalId\":8733,\"journal\":{\"name\":\"Basic & Clinical Pharmacology & Toxicology\",\"volume\":\"136 3\",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786297/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Basic & Clinical Pharmacology & Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/bcpt.70000\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Basic & Clinical Pharmacology & Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/bcpt.70000","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
氟伏沙明(FLV)是一种选择性血清素再摄取抑制剂,通常用于治疗焦虑、重度抑郁症和强迫症,以及其他精神疾病。本研究旨在评估FLV减轻脂多糖(LPS)对女性生殖道损伤的有效性。将32只雌性Wistar Albino大鼠随机分为对照组、LPS组、LPS-FLV组和FLV组。实验结束时,取卵巢、输卵管和子宫组织进行组织学、免疫组化和遗传分析。LPS组组织学检查显示轻度至中度出血、水肿及中性粒细胞浸润。此外,还有子宫内膜损伤和输卵管纤毛脱落的迹象。免疫组化分析显示,LPS增加了核因子κ b (NF-κB)和阳离子依赖性甘露糖6-磷酸受体(CD-MPR)的表达,降低了kisspeptin-1 (KISS-1)的表达。遗传分析表明,LPS增加了nod样受体家族pyrin domain-containing 3 (NLRP3)和aquaporin4 (AQP4)基因的表达,降低了Claudin-1的表达。然而,所有这些不良反应都被FLV治疗逆转。研究结果表明,FLV可能对治疗lps引起的女性生殖系统损伤有益。
Fluvoxamine Inhibited NLRP3 and NF-κB Inflammatory Pathways and Maintained Genital Functions by Ameliorating CD-MPR, KISS-1, AQP4 and Claudin-1 Expressions
Fluvoxamine (FLV), a selective serotonin reuptake inhibitor, is commonly used to treat anxiety, major depressive disorder and obsessive-compulsive disorder, among other psychiatric conditions. This study aims to evaluate the effectiveness of FLV in mitigating damage caused by lipopolysaccharide (LPS) to the female genital tract. Thirty-two female Wistar Albino rats were randomly divided into four groups: control, LPS, LPS-FLV and FLV. At the end of the experimental period, tissues from the ovaries, fallopian tubes and uterus were collected for histological, immunohistochemical and genetic analyses. Histological examination of the LPS group revealed mild to moderate bleeding, oedema and neutrophil infiltration. Additionally, there were signs of endometrial damage in the uterus and loss of cilia in the fallopian tubes. Immunohistochemical analysis showed that LPS increased the expressions of nuclear factor kappa beta (NF-κB) and cation-dependent mannose 6-phosphate receptors (CD-MPR) and reduced kisspeptin-1 (KISS-1) expression. Genetic analysis indicated that LPS increased the expression of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) and aquaporin4 (AQP4) genes while decreasing Claudin-1 expression. However, all these adverse effects were reversed by FLV treatment. The study's findings suggest that FLV may be beneficial in treating LPS-induced damage to the female reproductive system.
期刊介绍:
Basic & Clinical Pharmacology and Toxicology is an independent journal, publishing original scientific research in all fields of toxicology, basic and clinical pharmacology. This includes experimental animal pharmacology and toxicology and molecular (-genetic), biochemical and cellular pharmacology and toxicology. It also includes all aspects of clinical pharmacology: pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, drug/drug interactions, pharmacogenetics/-genomics, pharmacoepidemiology, pharmacovigilance, pharmacoeconomics, randomized controlled clinical trials and rational pharmacotherapy. For all compounds used in the studies, the chemical constitution and composition should be known, also for natural compounds.