Vitamin K Tissue Distribution Is Modified by Large-Dose Warfarin and Menaquinone-4 Content of the Diet
Bibliographic record
Abstract
Investigate the influence of large-dose warfarin (W) on tissue K1 and MK-4 distribution in rats fed a standard K1 diet, or enriched with MK4. Male Wistar rats were fed a regular K1 (750 mcg K1/kg/diet; WK1) or enriched MK-4 (100 mg MK-4/kg/diet; WK1 + MK4) diet for 1 week after which they were administered 14 mg W/kg/day (in drinking water) and subcutaneous K1 (94 mg/kg, 3X/week; to maintain coagulation), for 12 weeks; diets were maintained throughout the experimental period. Respective diet controls (C and C + MK4) received subcutaneous saline and regular water. K1 and M-4 quinone and their epoxide forms (K1O and MK-4O) were assessed in serum, liver, heart, kidney, pancreas, adipose tissue and brain, by HPLC. Group differences were tested by one-way ANOVA, and by t-test for each K vitamer. In C group, K1 was the predominant K vitamer in serum, liver and heart, whereas MK-4 was found in relative higher concentrations in kidney, pancreas, brain, and adipose tissue. In MK-4 containing organs, W treatment was associated with significantly lower MK-4 concentration in pancreas, brain, and heart (P < 0.05) despite the local presence of K1, which suggests that W may block the production of MK-4 by UBIAD1. Compared to C group, K1 concentrations were significantly higher in all organs and serum in WK1 and WK1 + MK4 groups as a result of the subcutaneous administration. Interestingly, in WK1 animals who had received a MK-4 enriched diet (WK1 + MK4), K1 concentrations in naturally K1 rich tissues (i.e., liver, heart and serum) were significantly increased when compared to those from the WK1 group (P < 0.05), suggesting that dietary MK-4 may play a role in modulating the uptake of K1 in these tissues. Except in liver, W administration (WK1 and WK1 + MK4) was associated with higher tissue concentrations of K1 and MK-4 epoxide when compared to C group (P < 0.05). Noteworthy, in WK1 animals who had received a MK-4 enriched diet (WK1 + MK4), naturally rich MK-4 containing organs (i.e., kidney, pancreas, adipose tissue and brain) presented significantly higher concentration of MK-4 epoxide (relative to K1 epoxide), suggesting a preferential use of MK4 by these organs when available from the diet. In conclusion, results from this study point to modulatory roles of W and dietary MK-4 on tissue distribution of K1 and MK-4 in what appears to be a tissue specific manner. CIHR.
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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".