Mitochondrial function after bisphenol S exposure: a safe substitute for BPA?
Bibliographic record
Abstract
Objective Bisphenol A (BPA) is one of the most common industrial chemicals, detected in the urine of 93 percent of US adults. BPA was declared a toxic substance in 2010 and has been linked to metabolic and cardiovascular disease. Amid growing consumer concern, manufacturers increasingly turned to BPA substitutes, the most common of which is bisphenol S (BPS); however, its safety was not determined before introduction to market. Thus, exposure to BPS is on the rise; but its health effects are unclear. Our aim was to determine the impact of BPS exposure on mitochondrial dynamics in vascular smooth muscle cells. Methods Vascular smooth muscle cells (VSMC) were isolated by enzymatic digestion from the thoracic aorta of juvenile (6–7 week old) male C56BL/6 mice. Cells were cultured in DMEM/F12 media supplemented with 10% fetal bovine serum and 1% penicillin‐streptomycin. At 70–80% confluency, cells were treated with vehicle (DMSO) or variable doses of BPS [2.5nM (levels in drinking water); 250nM (permissible limit) and 25μM]. Reactive oxygen species (ROS) levels from cellular and mitochondrial sources were determined by 2′,7′‐dichlorofluorescin diacetate (DCFDA) and MitoSOX staining, respectively. Membrane integrity was assessed by evaluating mitochondrial membrane potential (MMP) by JC1 staining. Mitochondrial fragmentation was measured by MitoTracker Red CMXROS staining and confocal microscopy. Real‐time PCR will be used to measure the expression of genes involved in mito‐fission and fussion and mitochondrial DNA copy number. Results After 30 min and 1 hr of BPS exposure, cellular and mitochondrial ROS levels were increased in a dose‐dependent manner, with a more prominent increase at 1 hr (all doses p<0.001). At 1, 12 and 24 hrs after exposure, mitochondrial depolarization was observed at all doses. At 24 hours, the reduction in mitochondrial membrane potential was greatest at the lowest dose (3‐fold vs. vehicle, p<0.0001). MitoTracker Red CMXROS revealed significant mitochondrial fragmentation at 24 hrs after exposure to 25μM BPS. Conclusion Mitochondrial function is disrupted in VSMCs exposed to BPS at doses lower than the permissible limit and equivalent to human exposure. Studies are underway to determine the mechanistic basis of BPS‐induced mitochondrial dysfunction and long‐term effects on vascular health. Support or Funding Information This study was supported the CIHR, Heart and Stroke Foundation of Canada, and a Kertland Fellowship.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".