van Furth, L.A. (2020) The effect of the ketogenic diet on mitochondrial function in porcine precision-cut kidney slices. thesis, Medicine.
Full text available on request.Abstract
Introduction: Kidneys derived from Donation after Circulatory Death (DCD) donors suffer more ischemic injury compared to Donation after Brain Deatch (DBD) donors. When after transplantation reperfusion occurs, the formation of Reactive Oxygen Species (ROS) contributes to the development of ischemia reperfusion injury (IRI). The major site of production and the major target of ROS are the mitochondria. Preoperative dietary restriction and fasting are known to be protective against renal IRI. During fasting or a ketogenic diet, the metabolic substrate switches from glucose to fatty acids, which then becomes the main source of adenosine triphosphate (ATP) production. Precision-cut kidney slices (PCKS) is an ex vivo model to evaluate intra- and extracellular mechanisms. Here, the aim is to evaluate the effect of a ketogenic diet on mitochondrial function using PCKS. Methods: Porcine kidneys were obtained at a local abattoir. After 30 min of warm ischemic time (WIT), kidneys were flushed and placed on hypothermic machine perfusion (HMP) and preserved for 3 hours with University of Wisconsin Cold Storage (UW-CS) solution. Thereafter PCKS were made and incubated at 37ºC with 80% oxygen. The incubation medium of the control group (n=5) consisted Roswell Park Memorial Institute (RPMI) 1640 medium, which contains 2 mg/mL glucose. The experimental groups consisted RPMI 1640 medium without glucose, supplemented with 2 mg/mL (±)-sodium 3-hydroxybutyrate (BHB) (n=5) or 1,5 mg/mL SMOFlipids® (SMOF) (n=5). Directly after slicing and after 24, 48 or 72 hours of incubation, tissue and medium samples were taken to analyse for different mitochondrial, oxidative stress and injury markers. Results: No differences were found in mitochondrial respiratory control rates. After 72 hours ATP levels were significantly higher in the control group compared to the BHB group. In the first 48 hours a significant increase in thiobarbituric acid reactive substances (TBARS) levels was seen in the SMOF group. Furthermore, no differences were found in TBARS levels. Over time significantly less lactate dehydrogenase (LDH) was seen in the SMOF group compared to the BHB group. No significant differences in aspartate aminotransferase (ASAT) levels were seen. Conclusion: A ketogenic diet has no beneficial effect on mitochondrial function in the PCKS model. Dietary modifications as a preconditioning strategy are promising, but more in-depth research must be performed.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Maassen, H. and Prof. Dr. Leuvenink, H.G.D. |
| Faculty: | Medical Sciences |
| Date Deposited: | 19 Sep 2023 11:34 |
| Last Modified: | 19 Sep 2023 11:34 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/3689 |
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