Impact of fatty acids on low-level lead (Pb) absorption and cellular stress
Bibliographic record
Abstract
Cardiovascular disease (CVD) is a leading cause of premature mortality. Fibrosis of the heart is a major contributor to chronic CVD pathology. Oxidative stress resulting from, an imbalance of oxidizers and antioxidants, is a major player in the development of CVD. Both exposure to heavy metals, like lead (Pb), and the overconsumption of omega-6 polyunsaturated fatty acids (PUFAs) have separately been linked with increased oxidative stress and fibrosis. Regulatory bodies have deemed certain blood Pb levels as acceptable, but Pb levels are misrepresented, and evidence shows that these ‘allowable’ levels are unsafe. Given the preponderance of omega-6 PUFA and Pb in the Canadian food supply, this investigates the interactions between Pb and fatty acids (FAs) on markers of cellular oxidative stress and fibrosis work for the first time. Two murine cell models, NIH-3T3 fibroblasts and RAW 264.7 macrophages, were used as models of fibrosis formation and inflammation respectively were used. The PUFA, linoleic acid (LA) and a saturated fatty acid, palmitic acid (PA) were used to study cellular absorption parameters of Pb. In chapter 2, dose-response studies were conducted to determine what levels of Pb, could keep cells alive and allow them to show stress responses over 24 hours. Chapter 3 investigated Pb absorption using an intracellular Pb-specific fluorescent probe and found that Pb absorption in fibroblasts and macrophages was decreased by the presence of both FA. It was further shown that exposure of RAW 264.7 macrophage cells to 5uM Pb and 25uM LA induced more Pb absorption than 5uM Pb and 25uM PA. This could indicate that omega-6 PUFA can promote Pb absorption greater than a saturated fatty acid. Chapter 4 concludes with investigation into the gene expression of various antioxidizing genes and membrane proteins that transport Pb, both of which can play a critical role in oxidative stress and fibrosis. Overall, these results give an initial understanding of Pb and FA interactions at the cellular level, in hopes that this provides the initial step in justifying the need of continued investigation into the synergistic roles of low-level Pb exposure and dietary fats towards cellular stress and CVD.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".