D‐Lactate Disturbed Mitochondrial Energy Production in Rat Brain and Heart but not Liver
Bibliographic record
Abstract
High D-lactate concentrations are associated with neurological and cardiac toxicity in both humans and animals. The neurological symptoms are similar to those of inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that intracellular D-lactate (DLA) inhibits mitochondrial uptake of L-lactate (LLA) and/or pyruvate, thereby decreasing mitochondrial energy production. In our study, respiration rates in rat brain, heart and liver mitochondria using DLA, LLA and pyruvate alone or in combination were measured. In brain (heart), DLA had 53% and 75% (39% and 86%) lower state 3 respiration rates (S3) and 49% and 72% (38% and 66%) lower respiratory control ratios (RCR) compared to LLA and pyruvate, respectively (p<0.05). DLA also reduced S3 and RCR of LLA and pyruvate in brain and heart (p<0.05). DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase LDH activities were similar across tissues. In the presence of a LDH inhibitor, LLA reduced S3 and RCR values of pyruvate in all tissues. Respiration was also inhibited by the monocarboxylate transporter inhibitor with DLA, LLA or pyruvate as substrates. In conclusion, DLA was a poor respiratory substrate and inhibited LLA and pyruvate usage in brain and heart. This may explain, in part, the neurological and cardiac toxicity caused by high DLA levels. This work was funded by Natural Sciences and Engineering Research Council of Canada.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".