Hala A Ahmed, Ahmed A Shaaban, Tarek M Ibrahim, Mirhan N Makled
{"title":"G 蛋白偶联雌激素受体激活可减轻 C57BL/6 小鼠顺铂诱导的 CKD:洞察性别差异","authors":"Hala A Ahmed, Ahmed A Shaaban, Tarek M Ibrahim, Mirhan N Makled","doi":"10.1016/j.fct.2024.115079","DOIUrl":null,"url":null,"abstract":"<p><p>Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) post-cisplatin therapy. This study aims at investigating the potential effect of G1 compound, a GPER agonist, on attenuating cisplatin-induced CKD. To induce CKD in male, intact female, and ovariectomized (OVX) mice, CKD was induced by injecting two cycles of 2.5 mg/kg cisplatin with a 16-day recovery period between cycles). G1 (50 or 100 μg/kg was administered daily for 6 weeks. Severity of renal damage was more pronounced in males than females. Interestingly, OVX resulted in renal damage that is non-significant compared to males and significantly higher than females. G1 improved renal function and blood flow as evidenced by reduction of serum creatinine and elevation of creatinine clearance, NO production, and reduction of ET1. This renoprotective effect could be attributed to its immunomodulatory effect regulated by TGF-β that shifted the balance to favor anti-inflammatory cytokine production (increased IL-10) rather than pro-inflammatory cytokines (decreased Th17 expression). Reduction of TGF-β activation also inhibited epithelial-to-mesenchymal transition that eventually ameliorated CKD development. Antioxidant potential of G1 has been demonstrated by upregulation of Nrf2 and subsequent antioxidant enzymes. These data suggest that G1 could be a promising therapeutic tool to attenuate CP-induced CKD.</p>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"G protein-coupled estrogen receptor activation attenuates cisplatin-induced CKD in C57BL/6 mice: An insight into sex-related differences.\",\"authors\":\"Hala A Ahmed, Ahmed A Shaaban, Tarek M Ibrahim, Mirhan N Makled\",\"doi\":\"10.1016/j.fct.2024.115079\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) post-cisplatin therapy. This study aims at investigating the potential effect of G1 compound, a GPER agonist, on attenuating cisplatin-induced CKD. To induce CKD in male, intact female, and ovariectomized (OVX) mice, CKD was induced by injecting two cycles of 2.5 mg/kg cisplatin with a 16-day recovery period between cycles). G1 (50 or 100 μg/kg was administered daily for 6 weeks. Severity of renal damage was more pronounced in males than females. Interestingly, OVX resulted in renal damage that is non-significant compared to males and significantly higher than females. G1 improved renal function and blood flow as evidenced by reduction of serum creatinine and elevation of creatinine clearance, NO production, and reduction of ET1. This renoprotective effect could be attributed to its immunomodulatory effect regulated by TGF-β that shifted the balance to favor anti-inflammatory cytokine production (increased IL-10) rather than pro-inflammatory cytokines (decreased Th17 expression). Reduction of TGF-β activation also inhibited epithelial-to-mesenchymal transition that eventually ameliorated CKD development. Antioxidant potential of G1 has been demonstrated by upregulation of Nrf2 and subsequent antioxidant enzymes. These data suggest that G1 could be a promising therapeutic tool to attenuate CP-induced CKD.</p>\",\"PeriodicalId\":317,\"journal\":{\"name\":\"Food and Chemical Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-11-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Food and Chemical Toxicology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1016/j.fct.2024.115079\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"FOOD SCIENCE & TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food and Chemical Toxicology","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1016/j.fct.2024.115079","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
G protein-coupled estrogen receptor activation attenuates cisplatin-induced CKD in C57BL/6 mice: An insight into sex-related differences.
Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) post-cisplatin therapy. This study aims at investigating the potential effect of G1 compound, a GPER agonist, on attenuating cisplatin-induced CKD. To induce CKD in male, intact female, and ovariectomized (OVX) mice, CKD was induced by injecting two cycles of 2.5 mg/kg cisplatin with a 16-day recovery period between cycles). G1 (50 or 100 μg/kg was administered daily for 6 weeks. Severity of renal damage was more pronounced in males than females. Interestingly, OVX resulted in renal damage that is non-significant compared to males and significantly higher than females. G1 improved renal function and blood flow as evidenced by reduction of serum creatinine and elevation of creatinine clearance, NO production, and reduction of ET1. This renoprotective effect could be attributed to its immunomodulatory effect regulated by TGF-β that shifted the balance to favor anti-inflammatory cytokine production (increased IL-10) rather than pro-inflammatory cytokines (decreased Th17 expression). Reduction of TGF-β activation also inhibited epithelial-to-mesenchymal transition that eventually ameliorated CKD development. Antioxidant potential of G1 has been demonstrated by upregulation of Nrf2 and subsequent antioxidant enzymes. These data suggest that G1 could be a promising therapeutic tool to attenuate CP-induced CKD.
期刊介绍:
Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs.
The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following:
-Adverse physiological/biochemical, or pathological changes induced by specific defined substances
-New techniques for assessing potential toxicity, including molecular biology
-Mechanisms underlying toxic phenomena
-Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability.
Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.