e652f036a91b1a0db7ac043a0b21f8e2 pmc_34679658.pdf 32fb6f08a549c4b6deb15ac3b4ff7b6b2c985d2d pmc_34679658.pdf 7a2ce398dcbcdd807956db5490fa8228f2579d26c1c16df23bffefb815d25628 pmc_34679658.pdf Title: Effects of Hypothermia and Allopurinol on Oxidative Status in a Rat Model of Hypoxic Ischemic Encephalopathy Subject: Hypoxic ischemic encephalopathy (HIE) is one of the main causes of morbidity and mortality during the neonatal period, despite treatment with hypothermia. There is evidence that oxidative damage plays an important role in the pathophysiology of hypoxic-ischemic (HI) brain injury. Our aim was to investigate whether postnatal allopurinol administration in combination with hypothermia would reduce oxidative stress (OS) biomarkers in an animal model of HIE. Postnatal 10-day rat pups underwent unilateral HI of moderate severity. Pups were randomized into: Sham operated, hypoxic-ischemic (HI), HI + allopurinol (HIA), HI + hypothermia (HIH), and HI + hypothermia + allopurinol (HIHA). Biomarkers of OS and antioxidants were evaluated: GSH/GSSG ratio and carbonyl groups were tested in plasma. Total antioxidant capacity (TAC) was analyzed in plasma and cerebrospinal fluid, and 8-iso-prostaglandin F2 was measured in brain tissue. Plasma 2,2'–azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) levels were preserved in those groups that received allopurinol and dual therapy. In cerebrospinal fluid, only the HIA group presented normal ferric reducing ability of plasma (FRAP) levels. Protein oxidation and lipid peroxidation were significantly reduced in all groups treated with hypothermia and allopurinol, thus enhancing neuroprotection in HIE. Keywords: allopurinol; hypothermia; hypoxic-ischemic encephalopathy; oxidative stress; oxidative damage Author: Cristina Durán Fernández-Feijóo, Javier Rodríguez-Fanjul, Miriam Lopez-Abat, Stephanie Hadley, Mónica Cavia-Saiz, Pilar Muñiz, Juan Arnaez, José Ramón Fernández-Lorenzo and Marta Camprubí Camprubí Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Sep 25 12:41:33 2021 CEST ModDate: Sat Sep 25 12:57:57 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1692188 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ZXDKIP+EURM10 Type 1 Builtin yes yes no 10 0 GCNTYP+URWPalladioL-Ital Type 1 Custom yes yes no 14 0 BHRZJL+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 QFMBZN+URWPalladioL-Roma 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Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 413 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Experimental Design Destination: subsection.2.1 Children: Item: Title: Allopurinol Destination: subsubsection.2.1.1 Item: Title: Hypothermia vs. Normothermia Destination: subsubsection.2.1.2 Item: Title: Samples Obtention and Preparation Destination: subsection.2.2 Item: Title: Sample Analysis Destination: subsection.2.3 Children: Item: Title: Plasma Total Antioxidant Capacity (TAC) Destination: subsubsection.2.3.1 Item: Title: Plasma Glutathione Reduced/Oxidized (GSH/GSSG) Ratio Analysis Destination: subsubsection.2.3.2 Item: Title: Plasma Protein Carbonyl Groups (CG) Destination: subsubsection.2.3.3 Item: Title: Brain 8-Iso-Prostaglandin F2 (8-iso-PGF2) Quantification Destination: subsubsection.2.3.4 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: Allopurinol Administration, Alone or in Combination with Hypothermia, Protects Total Antioxidant Capacity (TAC) after an HI Event Destination: subsection.3.1 Item: Title: GSH/GSSG Ratio Was Decreased after an HI Event, and Only Treated Groups Recovered to Normal Values Destination: subsection.3.2 Item: Title: TAC Levels in CSF Are Preserved When Allopurinol Is Administrated after an HI Event, but Not When Allopurinol Is Administrated in Combination with Hypothermia Destination: subsection.3.3 Item: Title: Protein Oxidation Increase after an HI Event, All Treatments Seem to Prevent Protein Oxidation Destination: subsection.3.4 Item: Title: Lipid Peroxidation Increased after an HI Event and Decreased in the Treated Groups Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Effects of Hypothermia and Allopurinol on Oxidative Status in a Rat Model of Hypoxic Ischemic Encephalopathy Author: Cristina Durán Fernández-Feijóo, Javier Rodríguez-Fanjul, Miriam Lopez-Abat, Stephanie Hadley, Mónica Cavia-Saiz, Pilar Muñiz, Juan Arnaez, José Ramón Fernández-Lorenzo and Marta Camprubí Camprubí Subject: Hypoxic ischemic encephalopathy (HIE) is one of the main causes of morbidity and mortality during the neonatal period, despite treatment with hypothermia. There is evidence that oxidative damage plays an important role in the pathophysiology of hypoxic-ischemic (HI) brain injury. Our aim was to investigate whether postnatal allopurinol administration in combination with hypothermia would reduce oxidative stress (OS) biomarkers in an animal model of HIE. Postnatal 10-day rat pups underwent unilateral HI of moderate severity. Pups were randomized into: Sham operated, hypoxic-ischemic (HI), HI + allopurinol (HIA), HI + hypothermia (HIH), and HI + hypothermia + allopurinol (HIHA). Biomarkers of OS and antioxidants were evaluated: GSH/GSSG ratio and carbonyl groups were tested in plasma. Total antioxidant capacity (TAC) was analyzed in plasma and cerebrospinal fluid, and 8-iso-prostaglandin F2 was measured in brain tissue. Plasma 2,2' azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) levels were preserved in those groups that received allopurinol and dual therapy. In cerebrospinal fluid, only the HIA group presented normal ferric reducing ability of plasma (FRAP) levels. Protein oxidation and lipid peroxidation were significantly reduced in all groups treated with hypothermia and allopurinol, thus enhancing neuroprotection in HIE. Keywords: allopurinol; hypothermia; hypoxic-ischemic encephalopathy; oxidative stress; oxidative damage Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Sep 25 12:41:33 CEST 2021 ModDate: Sat Sep 25 12:57:57 CEST 2021 ID: 0xa215e47bf8459291ca92b346f70184b4, 0xa215e47bf8459291ca92b346f70184b4 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: BHRZJL+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 FontDescriptor: FontName: BHRZJL+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: EIFDAO+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: EIFDAO+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QFMBZN+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: QFMBZN+URWPalladioL-Roma Flags: Symbolic FontBBox: 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