Concomitant Induction of Heme Oxygenase‐1 Attenuates the Cytotoxicity of Arsenic Species from <i>Lumbricus</i> Extract in Human Liver HepG2 Cells
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Bibliographic record
Abstract
Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme that degrades heme to three products, biliverdin, carbon monoxide (CO), and iron ion. The present study was originally designed to characterize the HO-1 induction by Lumbricus extract as a potential cytoprotective mechanism. Through bioactivity-guided fractionation, with human HepG2 cells as the cellular detector, surprisingly, we found that arsenic was enriched in the active fractions isolated from Lumbricus extract. Arsenic speciation was further carried out by liquid chromatography with inductively coupled plasma mass spectrometry (LC/ICP-MS). Our results showed that Lumbricus extract contained two major arsenic species, arsenite (As(III) ; 53.7%) and arsenate (As(V) ; 34.2%), and six minor arsenic species. Commercial sodium arsenite (NaAsO(2) ) was used to verify the effects of Lumbricus extract on HO-1 expression and related intracellular signaling pathways. Both p38 MAP kinase and NF-E2-related factor 2 (Nrf2) pathways were found to modulate HO-1 induction by Lumbricus extract and NaAsO(2) . The cytotoxicity of arsenite was augmented by p38 MAP kinase inhibitor SB202190 and HO-1 inhibitor tin protoporphyrin IX (SnPP), whereas p38 MAP kinase inhibitor SB202190 also inhibited HO-1 induction by NaAsO(2) . These results suggest that arsenic-containing compounds are responsible for HO-1 induction by Lumbricus extract. Although the exact role of toxic arsenic compounds in the treatment of oxidative injury remains unclear, concomitant HO-1 induction may be a key mechanism to antagonize the cytotoxicity of arsenic compounds in human cells.
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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 it