Effects of trivalent antimony on human erythrocyte glutathione-S-transferases
Bibliographic record
Abstract
Trivalent antimony (SB3+) in the form of potassium antimony tartrate was found to be an inhibitor of glutathione-S-transferases (GST) from human erythrocytes with a 50% inhibition concentration (IC50) of 0.05 mM. The inhibition was, however, incomplete with 15-20% of the GST activity remaining unaffected. In comparison, ethacrynic acid, a known inhibitor of GST, was tenfold more potent and affected close to 100% inhibition. Pentavalent antimony (SB5+) in the form of sodium stibogluconate had no effect on GST. Group V metalloids such as arsenite was slightly inhibitory, and arsenate was noninhibitory. When compared with five heavy metals, the inhibitory potency followed the order of SB3+ > Hg2+, Cu2+ > Cd 2+ > Cr3+ > Fe2+ x SB3+ inhibition of GST was competitive against the substrate 1-chloro-2,4-dinitrobenzene (CDNB) with an apparent Ki of 0.018 mM. Increasing the glutathione (GSH) concentration, however, produced a biphasic response: at concentrations below 1 mM, GSH was noncompetitive against SB3+, but at 1 mM and higher it was apparently competitive. A concurrent study of interactions between GSH, CDNB, and SB3+ showed that there was a significant nonenzymatic conjugation of CDNB at high GSH concentrations, which was suppressed by SB3+. The presence of albumin (500 mg/dL), or up to 5 mM N-acetylcysteine, cysteine, or ethylenediamine tetraacetic acid (EDTA) did not protect GST from the inhibitory effect of SB3+. The ability of erythrocyte GST to conjugate CDNB, which was measured directly by the formation of dinitrophenyl-glutathione (DNP-glutathione), was reduced by approximately 20 and 33%, respectively, in the presence of 2 and 10 mM SB3+, and nearly abolished with the addition of 0.2 mM ethacrynic acid. Based on these inhibition characteristics and the preferential accumulation of SB3+ in mammalian erythrocytes, it may be deduced that in the case of high antimonial intake, for example, during therapeutic treatment of Leishmaniasis, SB3+ levels in erythrocytes may be high enough to depress GST activity, which might compromise the ability of erythrocytes to detoxify electrophilic xenotbiotics.
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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 | 0.000 |
| 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".