Asmaa Adel, Manal Abdul-Hamid, Samraa H Abdel-Kawi, Mohamed A Abdelaziz, Hader I Sakr, Osama M Ahmed
{"title":"骨髓间充质干细胞可减少 CCl4 诱导的雄性 Wistar 大鼠肾损伤和纤维化。","authors":"Asmaa Adel, Manal Abdul-Hamid, Samraa H Abdel-Kawi, Mohamed A Abdelaziz, Hader I Sakr, Osama M Ahmed","doi":"10.1080/0886022X.2024.2319330","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl<sub>4</sub>) in Wistar rats.</p><p><strong>Methods: </strong>Following an intraperitoneal injection of CCl<sub>4</sub> (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 10<sup>6</sup> cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.</p><p><strong>Results: </strong>In CCl<sub>4</sub>-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl<sub>4</sub>-injected rats considerably reduced the previously noted abnormalities.</p><p><strong>Conclusions: </strong>By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl<sub>4</sub> injections.</p>","PeriodicalId":20839,"journal":{"name":"Renal Failure","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275530/pdf/","citationCount":"0","resultStr":"{\"title\":\"Bone marrow-derived mesenchymal stem cells reduce CCl<sub>4</sub>-induced kidney injury and fibrosis in male Wistar rats.\",\"authors\":\"Asmaa Adel, Manal Abdul-Hamid, Samraa H Abdel-Kawi, Mohamed A Abdelaziz, Hader I Sakr, Osama M Ahmed\",\"doi\":\"10.1080/0886022X.2024.2319330\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl<sub>4</sub>) in Wistar rats.</p><p><strong>Methods: </strong>Following an intraperitoneal injection of CCl<sub>4</sub> (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 10<sup>6</sup> cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.</p><p><strong>Results: </strong>In CCl<sub>4</sub>-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl<sub>4</sub>-injected rats considerably reduced the previously noted abnormalities.</p><p><strong>Conclusions: </strong>By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl<sub>4</sub> injections.</p>\",\"PeriodicalId\":20839,\"journal\":{\"name\":\"Renal Failure\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11275530/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Renal Failure\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/0886022X.2024.2319330\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Renal Failure","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/0886022X.2024.2319330","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/25 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:本研究探讨了大鼠和小鼠骨髓间充质干细胞(BM-MSCs)对四氯化碳(CCl4)导致的Wistar大鼠肾损伤和毒性的可能治疗作用:雄性 Wistar 大鼠腹腔注射四氯化碳(0.5 mL/kg b.w.,每周两次)八周后,每周静脉注射大鼠和小鼠间充质干细胞(1 × 106 cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week)四周。使用苏木精和伊红(H&E)、马森三色染色(MT)技术和电子显微镜分析对肾功能进行评估,并对肾脏样本进行检查。肾脏环氧化酶-2(COX-2)、蛋白 53(p53)和肿瘤坏死因子-α(TNF-α)通过免疫组化染色技术进行检测。此外,还鉴定了肾组织中氧化应激和抗氧化防御系统的生物指标:结果:注射了 CCl4 的大鼠血清肌酐、尿素和尿酸水平显著升高,肾脏脂质过氧化物(LPO)也显著升高,而肾脏中的超氧化物歧化酶、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽(GSH)转移酶和 GSH 水平显著下降。从组织学角度看,肾脏显示出多种结构异常,如肾小球萎缩、肾小管扩张、炎性白细胞浸润、成纤维细胞增殖和胶原蛋白含量升高。COX-2 和 TNF-α 等炎性细胞因子以及促凋亡介质 p53 均显著上调。用注射了四氯化碳的小鼠和大鼠的骨髓间充质干细胞处理大鼠,大大减少了之前提到的异常情况:结论:通过增强抗氧化防御、减少细胞凋亡和炎症,小鼠和大鼠的骨髓间充质干细胞能够增强注射了四氯化碳的大鼠的肾功能和组织学完整性。
Bone marrow-derived mesenchymal stem cells reduce CCl4-induced kidney injury and fibrosis in male Wistar rats.
Aim: This study explores the possible therapeutic role of rats and mice bone marrow-derived mesenchymal stem cells (BM-MSCs) on renal damage and toxicity brought on by carbon tetrachloride (CCl4) in Wistar rats.
Methods: Following an intraperitoneal injection of CCl4 (0.5 mL/kg b.w. twice weekly) for eight weeks, male Wistar rats were intravenously treated with rats and mice BM-MSCs (1 × 106 cells in 0.2 mL Dulbecco's Modified Eagle Medium (DMEM)/rat/week) a week for four weeks. Kidney functions were evaluated and kidney samples were examined using hematoxylin and eosin (H&E), Masson's trichrome (MT) staining techniques, and electron microscopy analysis. Kidney cyclooxygenase-2 (COX-2), protein 53 (p53), and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical staining techniques. Additionally, bioindicators of oxidative stress and antioxidant defense systems were identified in kidney tissue.
Results: In CCl4-injected rats, serum creatinine, urea, and uric acid levels significantly increased, as did renal lipid peroxidation (LPO), while superoxide dismutase, glutathione peroxidase (GPx), glutathione (GSH) transferase, and GSH levels significantly dropped in the kidneys. Histologically, the kidneys displayed a wide range of structural abnormalities, such as glomerular shrinkage, tubular dilations, inflammatory leukocytic infiltration, fibroblast proliferation, and elevated collagen content. Inflammatory cytokines like COX-2 and TNF-α as well as the pro-apoptotic mediator p53 were considerably upregulated. Treatment of BM-MSCs from mice and rats with CCl4-injected rats considerably reduced the previously noted abnormalities.
Conclusions: By boosting antioxidant defense and reducing apoptosis and inflammation, BM-MSCs from mice and rats were able to enhance kidney function and histological integrity in rats that had received CCl4 injections.
期刊介绍:
Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.