Modulation of the metabolism of <i>cis</i>-platin in blood plasma by glutathione
Bibliographic record
Abstract
The anticancer drug cis-platin (CP) is in worldwide clinical use to treat a variety of cancers, but is inherently associated with severe toxic side effects. Previous animal studies revealed that its neurotoxicity can be significantly reduced by the coadministration of l-glutathione (GSH) without affecting the anticancer effect. The underlying molecular mechanism, however, has remained elusive. Since the bloodstream is a likely biological compartment where CP-derived hydrolysis products may react with GSH, we have employed a recently developed metallomics tool to gain insight into the interaction of CP and GSH in rabbit plasma in vitro. After the addition of increasing GSH/CP molar ratios to plasma (25:1, 50:1, and 100:1), the determination of the Pt distribution 5 min and 2 h later revealed the formation of a Pt–GSH complex that did not bind to plasma proteins. The simultaneously obtained Zn distribution in plasma revealed a progressively more pronounced perturbation of the Zn metalloproteome with increasing GSH/CP molar ratios at the 5 min time point, which partially reversed at the 2 h time point. The formation of Pt–GSH species in plasma is therefore likely to be directly involved in the process by which GSH protects mammalian organisms from CP-induced neurotoxicity, nephrotoxicity, and possibly other organ-based toxicities.
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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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".