Interdependent toxicity mechanisms of oxidative stress, thiamin deficiency and alpha-oxoaldehydes
Bibliographic record
Abstract
Oxidative stress and thiamin deficiency are prevalent in diseases such as diabetes mellitus. An increase in oxidative stress and thiamin deficiency leads to an increase in alpha-oxoaldehydes (i.e. reactive dicarbonyls, glyoxal and methylglyoxal (MG)) which are known to be cytotoxic. This thesis investigated the relationship between alpha-oxoaldehyde induced oxidative stress, thiamin deficiency and toxicity. Chapter 2 describes the molecular mechanisms of rat hepatocyte cytotoxicity induced by the alpha-oxoaldehyde, glyoxal. An increase in reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) depletion and a decrease in mitochondrial membrane potential were observed before glyoxal-induced cell death occurred. Glyoxal-induced oxidative stress and cytotoxicity were prevented by aminoguanidine, D-penicillamine and pyridoxamine. Chapter 3 describes the role of thiamin in glyoxal detoxification by maintaining cellular NADPH levels. Under thiamin deficient conditions, glyoxal cytotoxicity and oxidative stress were increased. These were prevented by supplementing the media with 3 mM thiamin or 5 mM benfotiamine (lipophilic derivative of thiamin). In Chapters 4 and 5, rats exposed to exogenous oxidative stress and dietary thiamin deficiency resulted in increased levels of plasma glyoxal/MG and their hydroimidazolone protein adducts. In chapter 5, rats given a heat treated diet (thermolyzed diet) that was low in thiamin resulted in decreased GSH and increased levels of liver and colon oxidative stress biomarkers such as nitrotyrosine, protein carbonyls and hydroimidazolones. There was also an increased infiltration of macrophages in the colon indicating that inflammation had occurred. Increased alpha-oxoaldehyde levels led to an increased body burden of advanced glycation end products (AGES) which decreased GSH dependent antioxidant defenses. Thiamin deficiency and oxidative stress produced high levels of endogenous glyoxal/MG that could increase the risk of pre-neoplastic or neoplastic conditions in the colon.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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 teacher head, 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".