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Melatonin as a novel cardioprotective therapy in pulmonary hypertension
Includes bibliographical references.
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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Department of Medicine
2015
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| _version_ | 1867613251301277696 |
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| access_status_str | Open Access |
| author | Maarman, Gerald Jerome |
| author2 | Lecour, Sandrine |
| author_browse | Lecour, Sandrine Maarman, Gerald Jerome |
| author_facet | Lecour, Sandrine Maarman, Gerald Jerome |
| author_sort | Maarman, Gerald Jerome |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/12872 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:10.259Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Department of Medicine |
| publisherStr | Department of Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/12872 Melatonin as a novel cardioprotective therapy in pulmonary hypertension Maarman, Gerald Jerome Lecour, Sandrine Sliwa-Hahnle, Karen Medicine Includes bibliographical references. Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure which leads to right ventricular hypertrophy and failure. The mechanism involved in the pathophysiology of the disease remains unclear but it is suggested that oxidative stress may trigger cardiovascular dysfunction associated with the disease. To date, there is no efficient therapy against PH and novel therapies are urgently needed. Melatonin is a powerful antioxidant that can confer benefit against ischemia-reperfusion injury and hypertension. We therefore hypothesised that melatonin may confer cardiovascular benefits against PH. Methods: Oxidative stress (plasma lipid peroxidation, antioxidant capacity and antioxidant enzyme activity) was assessed in healthy (n=10), in patients with PH (n=10), in Long Evans rats (n≥6) or in a rat model of PH induced 28 days after the injection of monocrotaline (MCT, 80mg/kg, subcutaneous) (n≥6). Melatonin (75ng/L, nutritional concentration), 4mg/kg or 6mg/kg (therapeutic dose) was given daily in the drinking water of rats, with the treatment started 5 days before the injection of MCT, on the day of the injection or 14 days after the injection of MCT. The development of PH was measured by assessing right ventricular hypertrophy, cardiac fibrosis, oxidative stress and cardiac function (via echocardiography and the isolated heart Langendorff perfusion model). Results: Plasma oxidative stress was increased in both patients and rats with PH compared with their respective controls. A chronic treatment with melatonin (75ng/L, 4mg/kg or 6mg/kg) starting on the day of the injection with MCT in rats with PH reduced right ventricular hypertrophy, cardiac dysfunction and plasma oxidative stress compared with control rats. Furthermore, the beneficial effect of melatonin (6mg/kg) could be observed when given as a preventive (5 days prior to the injection of MCT) or as a curative therapy (14 days after the injection of MCT). Conclusions: Our data demonstrate that chronic treatment of melatonin confers cardioprotection in a rat model of PH. As melatonin is inexpensive, safe (no reported side effects) and already available over the counter in many countries, we propose that melatonin should be considered as a novel preventive/curative therapy to limit cardiac dysfunction in patients with PH. 2015-05-26T14:15:48Z 2015-05-26T14:15:48Z 2014 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/12872 eng application/pdf Department of Medicine Faculty of Health Sciences University of Cape Town |
| spellingShingle | Medicine Maarman, Gerald Jerome Melatonin as a novel cardioprotective therapy in pulmonary hypertension |
| thesis_degree_str | Doctoral |
| title | Melatonin as a novel cardioprotective therapy in pulmonary hypertension |
| title_full | Melatonin as a novel cardioprotective therapy in pulmonary hypertension |
| title_fullStr | Melatonin as a novel cardioprotective therapy in pulmonary hypertension |
| title_full_unstemmed | Melatonin as a novel cardioprotective therapy in pulmonary hypertension |
| title_short | Melatonin as a novel cardioprotective therapy in pulmonary hypertension |
| title_sort | melatonin as a novel cardioprotective therapy in pulmonary hypertension |
| topic | Medicine |
| url | http://hdl.handle.net/11427/12872 |
| work_keys_str_mv | AT maarmangeraldjerome melatoninasanovelcardioprotectivetherapyinpulmonaryhypertension |