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Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis
Thesis (MSc)--Stellenbosch University, 2025.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867613779587497984 |
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| access_status_str | Open Access |
| author | Jepson, Tayla |
| author2 | Smith, Carine |
| author_browse | Jepson, Tayla Smith, Carine |
| author_facet | Smith, Carine Jepson, Tayla |
| author_sort | Jepson, Tayla |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (MSc)--Stellenbosch University, 2025. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/134642 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:41:34.416Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/134642 Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis Jepson, Tayla Smith, Carine Ollewagen, Tracey Van Rensburg, Roland Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Division of Clinical Pharmacology. Systemic lupus erythematosus -- Pathogenesis Lupus nephritis -- Treatment Kidneys -- Fibrosis Autoimmune diseases Thesis (MSc)--Stellenbosch University, 2025. Jepson, T. 2025. Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis. Unpublished masters thesis. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/1ed1356e-bd9b-4b34-813f-3d28e3e09f0a ENGLISH ABSTRACT: Background & aim: Systemic lupus erythematosus (SLE) is a complex autoimmune disease. A major comorbidity, lupus nephritis, often progresses to chronic kidney disease (CKD), renal fibrosis, and death. Current treatments primarily target immune modulation, while the fibrotic mechanisms driving myofibroblast conversion remain understudied. Effective immunomodulators and antifibrotics are often inaccessible or unaffordable in resource-limited settings. This thesis aimed to develop and characterise a novel lupus nephritis-like fibrosis model in larval zebrafish, with which to comparatively assess the fibrosis-limiting potential of drugs currently used in SLE treatment, as well as drug candidates identified for repurposing. Methods: A zebrafish larval model of bisphenol A-induced chronic inflammation was superimposed onto an aristolochic acid-induced model of renal damage. The renal fibrosis model (RF) was then validated using prednisolone (a commonly used standard rescue treatment in zebrafish larvae in the context of inflammation) as treatment. Secondly, the model was employed in a drug screening study to assess the fibrosis-limiting potential of drugs commonly prescribed in SLE (hydroxychloroquine (HCQ), methotrexate, mycophenolate mofetil) and potential drug repurposing candidates (metformin, rapamycin, tacrolimus, pirfenidone). Finally, drugs showing high fibrosis-limiting potential (attenuated sickness behaviour, beneficial modulation of transforming growth factor-beta and bone morphogenetic protein-7 concentrations) were assessed more comprehensively using immunohistochemistry and quantitative fluorescent microscopy, as well as in vivo renal function testing to probe the potential mechanisms involved. Results: The model showed robustness, with consistent results in the RF vs control groups in repeated execution of the model. The sensitivity of the chosen screening criteria was validated by the positive results obtained for prednisolone. The study demonstrated fibrosis-limiting and renal functional normalisation capacity of hydroxychloroquine and tacrolimus. Conclusion: This study presents an SLE-relevant zebrafish model of renal fibrosis, facilitating evaluation of current and repurposed SLE therapies. Tacrolimus exhibited fibrosis-limiting effects but with safety concerns, while HCQ showed a more favourable risk profile. Despite limitations, the model remains a valuable tool for drug screening in the context of lupus nephritis (LN). AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Masters 2025-12-22T06:03:04Z 2025-12-22T06:03:04Z 2025-12 Thesis https://scholar.sun.ac.za/handle/10019.1/134642 en Stellenbosch University 85 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Systemic lupus erythematosus -- Pathogenesis Lupus nephritis -- Treatment Kidneys -- Fibrosis Autoimmune diseases Jepson, Tayla Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis |
| title | Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis |
| title_full | Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis |
| title_fullStr | Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis |
| title_full_unstemmed | Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis |
| title_short | Comparative assessment of anti-fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis-associated fibrosis |
| title_sort | comparative assessment of anti fibrotic potential of drugs using an in vivo zebrafish model of lupus nephritis associated fibrosis |
| topic | Systemic lupus erythematosus -- Pathogenesis Lupus nephritis -- Treatment Kidneys -- Fibrosis Autoimmune diseases |
| url | https://scholar.sun.ac.za/handle/10019.1/134642 |
| work_keys_str_mv | AT jepsontayla comparativeassessmentofantifibroticpotentialofdrugsusinganinvivozebrafishmodeloflupusnephritisassociatedfibrosis |