f8c9056f4cd3c79c3017c62dd0f247bf 301306.pdf b39d6c4cfb7ad17ca0e553fa752d872ba9ad4c24 301306.pdf f4a25ba3fb74ca5050f18dac7ae3ac03b8be3c2d32563c7ffb9ae37e55df9d2e 301306.pdf Title: The 3Rs in Experimental Liver Disease Subject: Patients with cirrhosis present multiple physiological and immunological alterations that play a very important role in the development of clinically relevant secondary complications to the disease. Experimentation in animal models is essential to understand the pathogenesis of human diseases and, considering the high prevalence of liver disease worldwide, to understand the pathophysiology of disease progression and the molecular pathways involved, due to the complexity of the liver as an organ and its relationship with the rest of the organism. However, today there is a growing awareness about the sensitivity and suffering of animals, causing opposition to animal research among a minority in society and some scientists, but also about the attention to the welfare of laboratory animals since this has been built into regulations in most nations that conduct animal research. In 1959, Russell and Burch published the book “The Principles of Humane Experimental Technique”, proposing that in those experiments where animals were necessary, everything possible should be done to try to replace them with non-sentient alternatives, to reduce to a minimum their number, and to refine experiments that are essential so that they caused the least amount of pain and distress. In this review, a comprehensive summary of the most widely used techniques to replace, reduce, and refine in experimental liver research is offered, to assess the advantages and weaknesses of available experimental liver disease models for researchers who are planning to perform animal studies in the near future. Keywords: replacement; refinement; reduction; liver; research; disease Author: Sebastian Martinez-Lopez, Enrique Angel-Gomis, Elisabet Sanchez-Ardid, Alberto Pastor-Campos, Joanna Picó and Isabel Gomez-Hurtado Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 25 12:28:32 2023 CEST ModDate: Wed Jul 26 11:26:06 2023 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 32 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 953701 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SOZKOC+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 HDYAMO+VnURWPalladioL Type 1 Custom yes yes no 15 0 FRHMYB+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 EFPMPU+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 KJLNNE+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 SZMRXJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 76 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 80 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 84 0 BCDIEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 88 0 BCDJEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 95 0 MEWEWT+CMSY10 Type 1 Builtin yes yes no 112 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 116 0 NUUXUW+VnURWPalladioL-Italic Type 1 Custom yes yes no 176 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-08 02:39:56 CEST RepresentationInformation: 301306.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-10-07 11:24:46 CEST Size: 953701 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 962 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: The 3RS from an Institutional Point of View Destination: section.2 Item: Title: Animal Models in Liver Disease Destination: section.3 Item: Title: 3RS in Experimental Models of Liver Disease Destination: section.4 Children: Item: Title: Replacement Destination: subsection.4.1 Children: Item: Title: 2D In Vitro Liver Models: Monocultures and Cocultures Destination: subsubsection.4.1.1 Item: Title: 3D In Vitro Liver Models Destination: subsubsection.4.1.2 Item: Title: Computational Models Destination: subsubsection.4.1.3 Item: Title: Refinement Destination: subsection.4.2 Children: Item: Title: Animal Husbandry and Monitoring Destination: subsubsection.4.2.1 Item: Title: Refinement in Liver Research Destination: subsubsection.4.2.2 Item: Title: Reduction Destination: subsection.4.3 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: The 3Rs in Experimental Liver Disease Author: Sebastian Martinez-Lopez, Enrique Angel-Gomis, Elisabet Sanchez-Ardid, Alberto Pastor-Campos, Joanna Picó and Isabel Gomez-Hurtado Subject: Patients with cirrhosis present multiple physiological and immunological alterations that play a very important role in the development of clinically relevant secondary complications to the disease. Experimentation in animal models is essential to understand the pathogenesis of human diseases and, considering the high prevalence of liver disease worldwide, to understand the pathophysiology of disease progression and the molecular pathways involved, due to the complexity of the liver as an organ and its relationship with the rest of the organism. However, today there is a growing awareness about the sensitivity and suffering of animals, causing opposition to animal research among a minority in society and some scientists, but also about the attention to the welfare of laboratory animals since this has been built into regulations in most nations that conduct animal research. In 1959, Russell and Burch published the book “The Principles of Humane Experimental Technique”, proposing that in those experiments where animals were necessary, everything possible should be done to try to replace them with non-sentient alternatives, to reduce to a minimum their number, and to refine experiments that are essential so that they caused the least amount of pain and distress. In this review, a comprehensive summary of the most widely used techniques to replace, reduce, and refine in experimental liver research is offered, to assess the advantages and weaknesses of available experimental liver disease models for researchers who are planning to perform animal studies in the near future. 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