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Open Access Research

D-Lactate altered mitochondrial energy production in rat brain and heart but not liver

Binbing Ling1, Fei Peng1, Jane Alcorn1, Katharina Lohmann2, Brian Bandy1 and Gordon A Zello1*

Author Affiliations

1 College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada

2 Large Animal Clinical Sciences, Western College of Veterinary Medicine, Saskatoon, SK, Canada

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Nutrition & Metabolism 2012, 9:6  doi:10.1186/1743-7075-9-6

Published: 1 February 2012

Abstract

Background

Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart.

Methods

Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination.

Results

In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p < 0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p < 0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p < 0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates.

Conclusions

DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels.

Keywords:
D-Lactate; Mitochondrial function; Rat; Brain; Heart