HYDROGEN SULFIDE-RELEASING ANTI-INFLAMMATORY DRUG ATB-340 TREATMENT POTENTIALLY REDUCES MESENTERIC METAFLAMMATION IN THE EXPERIMENTAL AGE- AND HIGH FRUCTOSE DIETARY-INDUCED INJURY
Bibliographic record
Abstract
Metaflammation (MF) is associated with visceral adiposities involved in the metabolic, cardiovascular, and gastrointestinal disease pathogenesis while their target therapeutic strategy is still limited. The link between mesenteric white adipocytes (MA) and stromal-vascular cellular remodeling in advanced age and Western diet consumption which is the base of MF remain undiscovered. Hydrogen Sulfide (H2S) non-steroidal anti-inflammatory drugs (H2S-NSAIDs) are a promising novel class of drugs regarding their cytoprotective, regulatory redox signaling, vasodilatory, and anti-inflammatory effects. Aim. To study the effectiveness of novel H2S-NSAIDs ATB-340, a hybrid compound of H2S and aspirin (ASA) over conventional ASA, and combination of ASA and NaHS on mesenteric cellular adaptive changes in experimental age- and high fructose dietary (HFD)-induced injury. Methods: Mesenteric subcellular adaptive responses of aged male rats on a standard diet (SD) or 4 weeks HFD that underwent acute water-immersion restraint stress (WIRS) were evaluated by electron microscopy. The effects of 9 days exogenous administration of ATB-340 (17.5 mg/kg/day), ASA (10 mg/kg/day) and sodium hydrosulfide (NaHS, 5.6 mg/kg/day) were investigated. Serum glucose level, thiobarbituric acid reactive substances (TBARS), and activities of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), thiosulfate-dithiol sulfurtransferase (TST), and sulfite oxidase (SO) were examined biochemically using spectrophotometry. Results: In HFD groups exposed to WIRS treatment with ATB-340 protected MA, as well their mitochondria, microvascular endothelial, and sub-endothelial structures, fibroblasts were observed vs the ASA and H2S+ASA-treated groups that had signs of endothelial dysfunction, MA damage with dysfunctional mitochondria, and mitochondria with fat incorporation. In rats fed with HFD and ASA treatment, low activities of CSE, CBS, TST and the rise of TBARS level and SO activity were observed. Treatment with ASA+NaHS, ATB-340 of aged rats lowered TBARS and enhanced H2S enzyme activities in contrast to the vehicle-treated group (p < 0.05). Conclusions. Mitochondrial alterations, endothelial damage, and redox disbalance are key factors for aged rat mesenteric adipose tissue remodeling during Western diet consumption. Our results contributing to identifying powerful intervention by effective compound H2S-ASA, novel H2S-NSAIDs, which has the potential to modulate mesenteric metaflammation, vascular function by enhancement H2S synthesis and redox regulatory and cytoprotective activities
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| 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".