Hennink, Marleen H.H. (2012) Pharmacological induction of hibernation: a useful strategy to reduce hepatocyte death induced by acetaminophen in vitro? thesis, Medicine.
Full text available on request.Abstract
Acute liver failure (ALF) is a rare condition in which severe liver injury rapidly develops. In Western countries, drug-induced liver injury has become the most important cause of ALF. The drug that accounts for most cases of ALF is acetaminophen (APAP). N-acetylcysteine (NAC) is the antidote for APAP overdose. However, NAC has to be administered to the patient within 8 hours, otherwise massive hepatocyte necrosis follows and in that case, the only remaining treatment option is liver transplantation. Since donor livers are scarce, new treatment options are needed. A possible therapeutic option for ALF involves induction of hibernation. Hibernating animals have shown to possess a natural protection against organ injury. Several compounds are proposed to induce a state that resembles hibernation and may consequently protect against organ damage in non-hibernators. In this research project, the protective role of several “hibernation compounds” is investigated in vitro after a hepatotoxic insult with APAP. Two hepatotoxicity cell models were used: HepG2 cells and primary rat hepatocytes (rHep). Cells were submitted to a toxic insult with APAP and treated with NaHS, 5’-AMP, serotonin, dopamine or NOD. Markers of hepatotoxicity were necrosis, apoptosis and viability, investigated by LDH measurement, Sytox Green staining, caspase-3 activity measurement, Acridine Orange staining and a MTS assay. A toxic insult with APAP induced apoptotic cell death in both HepG2 cells and rHep. Necrosis could not be assessed. From the investigated hibernation compounds only NaHS showed a cytoprotective effect. Serotonin did show some protective effects in HepG2 cells, but not in primary rat hepatocytes. 5’-AMP, dopamine and NOD were found to be cytotoxic in the used concentrations.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisors: and Henning, Prof R. H. and Clinical Pharmacology and and Verhaag, E. M. Gastroenterology and UMCG |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:01 |
| Last Modified: | 25 Jun 2020 11:01 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2103 |
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