Volska 2013 Abstract MiP2013

Volska K, Makrecka-Kuka M, Svalbe B, Dambrova M (2013) The inhibitor of L-carnitine biosynthesis protects brain mitochondria against anoxia-reoxygenation injury. Mitochondr Physiol Network 18.08.

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MiP2013, Book of Abstracts Open Access

Volska K, Makrecka-Kuka M, Svalbe B, Dambrova M (2013)

Event: MiP2013 Programme

L-carnitine takes part in the regulation of cellular energy metabolism. Recently it has been shown that mildronate, an inhibitor of L-carnitine biosynthesis, improves the neurological outcome after ischemic damage of brain tissue [1]. The aim of the present study was to investigate the effects of mildronate treatment on brain mitochondrial function using an in vitro model of anoxia-reoxygenation.

Wistar rats were treated daily with mildronate (per os; 100 mg/kg) for 14 days. Control animals received water. The mitochondrial respiration measurements were performed in isolated brain mitochondria with a Clark-type oxygen sensor. OXPHOS capacity was measured using ADP and various substrates to evaluate respiration of all respiratory complexes. In order to investigate anoxia-reoxygenation damage, brain mitochondria were subjected to 5 min anoxia, followed by 5 min reoxygenation. In parallel, isolated mitochondria were treated under the same conditions but without 5 min anoxia to obtain control (normoxic) measurements. Respiratory parameters were determined: LEAK respiration in the absence of ADP (LN); OXPHOS capacity (P); LEAK respiration after phosphorylation of ADP to ATP (LT); respiratory control ratio (P/LT, RCR).

Under normoxic conditions, mildronate treatment did not affect LN and P. However, LT was increased by 30%, resulting in a 28% decreased RCR. Anoxia-reoxygenation induced a significant 2.8-fold decrease in P and a 1.6-fold increase LT. These effects of anoxia-reoxygenation resulted in 4-fold reduction of the RCR. The mildronate treatment significantly diminished the anoxia-reoxygenation-induced decrease in P and increase in LT by 20% and 36%, respectively. After anoxia-reoxygenation the RCR was almost 2 times higher in the mildronate treated group compared to controls.

These results demonstrate that mildronate treatment induces uncoupling preconditioning-like effect and improves tolerance against anoxia-reoxygenation.

Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Ischemia-reperfusion;preservation"Ischemia-reperfusion;preservation" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.  Organism: Rat  Tissue;cell: Nervous system  Preparation: Isolated mitochondria 

Regulation: Coupling efficiency;uncoupling  Coupling state: LEAK, OXPHOS 

MiP2013 

Affiliations and author contributions

1 - Riga Stradins University, Latvia; 2 - Latvian Institute of Organic Synthesis, Riga, Latvia; 3 - University of Latvia, Riga, Latvia. - Email: k.volska@inbox.lv

References

1. Svalbe B, Zvejniece L, Vavers E, Pugovics O, Muceniece R, Liepinsh E, Dambrova M (2011) Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats. Behav Brain Res 222: 26-32.