Prooxidant and Antioxidant Activity of Vitamin E Analogues and Troglitazone
Bibliographic record
Abstract
The order of antioxidant effectiveness of low concentrations of vitamin E analogues, in preventing cumene hydroperoxide-induced hepatocyte lipid peroxidation and cytotoxicity, was 2,2,5,7,8-pentamethyl-6-hydroxychromane (PMC) > troglitazone > Trolox C > alpha-tocopherol > gamma-tocopherol > delta-tocopherol. However, vitamin E analogues, including troglitazone at higher concentrations, induced microsomal lipid peroxidation when oxidized to phenoxyl radicals by peroxidase/H2O2. Ascorbate or GSH was also cooxidized, and GSH cooxidation by vitamin E analogue phenoxyl radicals was also accompanied by extensive oxygen uptake and oxygen activation. When oxidized by nontoxic concentrations of peroxidase/H2O2, vitamin E analogues except PMC also caused hepatocyte cytotoxicity, lipid peroxidation, and GSH oxidation. The prooxidant order of vitamin E analogues in catalyzing hepatocyte cytotoxicity, lipid peroxidation, and GSH oxidation was troglitazone > Trolox C > delta-tocopherol > gamma-tocopherol > alpha-tocopherol > PMC. A similar order of effectiveness was found for GSH cooxidation or microsomal lipid peroxidation but not for ascorbate cooxidation. Except for troglitazone, the toxic prooxidant activity of vitamin E analogues was therefore inversely proportional to their antioxidant activity. The high troglitazone prooxidant activity could be a contributing factor to its hepatotoxicity. We have also derived equations for three-parameter quantitative structure-activity relationships (QSARs), which described the correlation between antioxidant and prooxidant activity of vitamin E ananlogues and their lipophilicity (log P), ionization potential (E(HOMO)), and dipole moment.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.000 |
| 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".