Farnesol mitigates methotrexate-induced intestinal toxicity by enhancing SIRT1, PPAR-γ, and Nrf2 signaling and attenuating Bax/cytochrome <i>c</i> /caspase-3–mediated apoptosis
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Bibliographic record
Abstract
Objectives The adherence to methotrexate (MTX) prolonged therapy in various cancers and autoimmune disorders is restricted due to its deleterious effects on several organs, like the liver, kidney, and intestine. Farnesol (FAR), a sesquiterpene alcohol found in various foods, essential oils, and herbs, exhibited promising antioxidant and anti-inflammatory impact in diverse experiments. The purpose of our study was to examine the possible mitigation of MTX-induced intestinal damage by FAR and the molecular pathways involved.Methods The rats were orally administered FAR (10 mg/kg) for 10 days and a single i.p. injection of MTX (20 mg/kg) on day 5. On day 11, samples of duodenal tissue were obtained for biochemical, histological, and molecular assessments.Results Our results demonstrated that FAR markedly ameliorated the degenerative changes induced by MTX in the duodenal mucosa along with preservation of mucosal goblet cells as manifested by PAS and Alcian blue staining. Besides, FAR enhanced the antioxidant and anti-inflammatory defenses via up-regulated expressions of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor-gamma (PPAR-γ), and nuclear factor erythroid 2-related factor 2 (Nrf2) proteins. Moreover, the anti-inflammatory activity of FAR was emphasized by the substantial decrease in tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) duodenal contents in MTX-treated rats. Ultimately, FAR reduced duodenal apoptosis by down-regulating Bcl-2-associated X protein (Bax), cytochrome c, and cleaved caspase-3, while up-regulating B-cell lymphoma 2 (Bcl-2) expression demonstrated by the immunohistochemical investigation.Conclusion: FAR could protect against intestinal toxicity caused by MTX and thus increase the tolerability and adherence to prolonged MTX therapy.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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