8b74bb2985e21974adb989003db1e14d pmc_33922431.pdf b671bb0b01009baa9df62f56349b255afc798ecd pmc_33922431.pdf da355e58d0238869a7853dc4554bece16debdb351f698c9773e486f9eeef7c2e pmc_33922431.pdf Title: Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress Subject: The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we evaluated the protective effects of CaD (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Results demonstrated that body weight loss, anxiety-like and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance in elevated plus-maze, Y-maze, and shuttle box tests. CaD treatment also inhibited the oxidative stress in aging mouse brains by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. These results could open new perspectives for the clinical use of CaD in treating and preventing cognitive impairment in older people. Keywords: aging; antioxidant activity; calcium dobesilate; Doxium; D-galactose; mice; oxidative stress Author: Elham Hakimizadeh, Mohammad Zamanian, Lydia Giménez-Llort, Clara Sciorati, Marjan Nikbakhtzadeh, Małgorzata Kujawska, Ayat Kaeidi, Jalal Hassanshahi and Iman Fatemi Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Apr 26 05:00:29 2021 CEST ModDate: Mon Apr 26 13:17:19 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: 1637220 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UYBGVU+VnURWPalladioL Type 1 Custom yes yes no 10 0 KPUTUB+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 XBVWJO+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 OSENDK+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 78 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 85 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:20:24 CEST RepresentationInformation: pmc_33922431.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:50 CEST Size: 1637220 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 310 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: Animals and Treatments Destination: subsection.2.1 Item: Title: Body Weight and Behavioral Tests Destination: subsection.2.2 Item: Title: Oxidative Stress Evaluation Destination: subsection.2.3 Item: Title: Statistical Analysis Destination: subsection.2.4 Item: Title: Results Destination: section.3 Children: Item: Title: CaD Inhibited the Body Weight Loss Induced by D-Gal Treatment Destination: subsection.3.1 Item: Title: CaD Decreased the Anxiety-Like Behavior in D-Gal Treated Mice Destination: subsection.3.2 Item: Title: CaD Attenuated the Cognitive Impairments in D-Gal Treated Mice Destination: subsection.3.3 Item: Title: CaD Reduced the Oxidative Stress s in D-Gal Treated Mice Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress Author: Elham Hakimizadeh, Mohammad Zamanian, Lydia Giménez-Llort, Clara Sciorati, Marjan Nikbakhtzadeh, Małgorzata Kujawska, Ayat Kaeidi, Jalal Hassanshahi and Iman Fatemi Subject: The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we evaluated the protective effects of CaD (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Results demonstrated that body weight loss, anxiety-like and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance in elevated plus-maze, Y-maze, and shuttle box tests. CaD treatment also inhibited the oxidative stress in aging mouse brains by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. These results could open new perspectives for the clinical use of CaD in treating and preventing cognitive impairment in older people. Keywords: aging; antioxidant activity; calcium dobesilate; Doxium; D-galactose; mice; oxidative stress Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Apr 26 05:00:29 CEST 2021 ModDate: Mon Apr 26 13:17:19 CEST 2021 ID: 0xbe68ee9746d257789d7dd7f6e7ff3822, 0xbe68ee9746d257789d7dd7f6e7ff3822 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: XBVWJO+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: XBVWJO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: VVSYYB+EURM10 FontSubset: true FirstChar: 11 LastChar: 22 FontDescriptor: FontName: VVSYYB+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: OSENDK+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: OSENDK+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: 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