Erdal Uysal, Mehmet Dokur, Faruk Kucukdurmaz, Serdar Altınay, Sait Polat, Kadir Batcıoglu, Efe Sezgın, Tuğçe Sapmaz Erçakallı, Aslı Yaylalı, Yakup Yılmaztekin, Zafer Cetın, İlker Saygılı, Osman Barut, Hatem Kazımoglu, Gokturk Maralcan, Suna Koc, Turkan Guney, Nadire Eser, Mehmet Sökücü, Sema Nur Dokur
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The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2'-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues.</p><p><strong>Results: </strong>Total tubular injury score was lower in the MNS group (<i>p</i> < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (<i>p</i> < 0.001). Apoptotic index (AI) was found to be low in the MNS group (<i>p</i> < 0.001). CAT and SOD levels were higher in the MNS Group (<i>p</i> = 0.006, <i>p</i> = 0.0004, respectively). GPx, MDA, and 8-OH-dG levels were similar (<i>p</i> > 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis.</p><p><strong>Conclusions: </strong>Our results suggested that MNS administrated before the reperfusion reduces pyroptosis, apoptosis and necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of Nod-like receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.</p>","PeriodicalId":16200,"journal":{"name":"Journal of Investigative Surgery","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"6","resultStr":"{\"title\":\"Targeting the PANoptosome with 3,4-Methylenedioxy-β-Nitrostyrene, Reduces PANoptosis and Protects the Kidney against Renal İschemia-Reperfusion Injury.\",\"authors\":\"Erdal Uysal, Mehmet Dokur, Faruk Kucukdurmaz, Serdar Altınay, Sait Polat, Kadir Batcıoglu, Efe Sezgın, Tuğçe Sapmaz Erçakallı, Aslı Yaylalı, Yakup Yılmaztekin, Zafer Cetın, İlker Saygılı, Osman Barut, Hatem Kazımoglu, Gokturk Maralcan, Suna Koc, Turkan Guney, Nadire Eser, Mehmet Sökücü, Sema Nur Dokur\",\"doi\":\"10.1080/08941939.2022.2128117\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-β-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury.</p><p><strong>Methods: </strong>Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2'-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues.</p><p><strong>Results: </strong>Total tubular injury score was lower in the MNS group (<i>p</i> < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (<i>p</i> < 0.001). Apoptotic index (AI) was found to be low in the MNS group (<i>p</i> < 0.001). 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引用次数: 6
摘要
目的:本研究的目的是:a)研究3,4-亚甲二氧基-β-亚硝基苯乙烯(MNS)靶向泛视体对肾缺血再灌注(RIR)模型中泛视症的影响;b)研究MNS对RIR损伤的肾脏保护作用。方法:将32只大鼠随机分为4组。将各组分为对照组、Sham组、DMSO(二甲基亚砜)组和MNS组。MNS组大鼠腹腔注射20 mg/kg MNS 30 再灌注前几分钟。DMSO组给予大鼠2%溶解MNS的DMSO溶剂。再灌注后6h,在麻醉下对大鼠进行左肾切除术。测定谷胱甘肽过氧化物酶(GPx)、丙二醛(MDA)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和8-Okso-2'-脱氧鸟苷(8-OHdG)水平。组织进行免疫组织化学分析、电镜和组织学检查。结果:MNS组肾小管损伤总分较低(p p p p = 0.006,p = 0.0004)。GPx、MDA和8-OH-dG水平相似(p > 0.05)。基于电子显微镜分析,MNS显著改善了组织结构。结论:再灌注前给予MNS可减少焦下垂、细胞凋亡和坏死。这些发现表明,MNS通过减少泛视症而显著保护肾脏免受RIR损伤,泛视症是由于对泛视体蛋白之一的含有Nod样受体pyrin结构域3(NLRP 3)的特异性抑制所致。
Targeting the PANoptosome with 3,4-Methylenedioxy-β-Nitrostyrene, Reduces PANoptosis and Protects the Kidney against Renal İschemia-Reperfusion Injury.
Objectives: The objectives of this study were a) to investigate the effect of targeting the PANoptosome with 3,4-methylenedioxy-β-nitrostyrene (MNS) on PANoptosis in the Renal ischemia-reperfussion (RIR) model b) to investigate the kidney protective effect of MNS toward RIR injury.
Methods: Thirty-two rats were divided into four groups randomly. The groups were assigned as Control, Sham, DMSO (dimethyl sulfoxide) and MNS groups. The rats in the MNS group were intraperitoneally given 20 mg/kg of MNS 30 minutes before reperfusion. 2% DMSO solvent that dissolves MNS were given to the rats in DMSO group. Left nephrectomy was performed on the rats under anesthesia at the 6th hour after reperfusion. Glutathione peroxidase (GPx), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and 8-Okso-2'-deoksiguanozin (8-OHdG) levels were measured. Immunohistochemical analysis, electron microscopic and histological examinations were carried out in the tissues.
Results: Total tubular injury score was lower in the MNS group (p < 0.001). Caspase-3, Gasdermin D and MLK (Mixed Lineage Kinase Domain Like Pseudokinase) expressions were considerably decreased in the MNS group (p < 0.001). Apoptotic index (AI) was found to be low in the MNS group (p < 0.001). CAT and SOD levels were higher in the MNS Group (p = 0.006, p = 0.0004, respectively). GPx, MDA, and 8-OH-dG levels were similar (p > 0.05) in all groups. MNS considerably improved the tissue structure, based on the electron microscopic analysis.
Conclusions: Our results suggested that MNS administrated before the reperfusion reduces pyroptosis, apoptosis and necroptosis. These findings suggest that MNS significantly protects the kidney against RIR injury by reducing PANoptosis as a result of specific inhibition of Nod-like receptor pyrin domain-containing 3 (NLRP 3), one of the PANoptosome proteins.
期刊介绍:
Journal of Investigative Surgery publishes peer-reviewed scientific articles for the advancement of surgery, to the ultimate benefit of patient care and rehabilitation. It is the only journal that encompasses the individual and collaborative efforts of scientists in human and veterinary medicine, dentistry, basic and applied sciences, engineering, and law and ethics. The journal is dedicated to the publication of outstanding articles of interest to the surgical research community.