Diclofenac Sodium Inhibits Hepatic Tryptophan 2,3-Dioxygenase but Augments Brain Indoleamine 2,3-Dioxygenase Activities in Rats
Bibliographic record
Abstract
Tryptophan 2,3-dioxygenase (TDO) exist only in liver while indoleamine 2, 3-dioxygenase (IDO) exists ubiquitously in the body, these are the most rate-limiting enzymes of kynurenine pathway (KP). In response to elevated levels of cortisol and pro-inflammatory cytokines, both enzymes show increase activity in patients with depression or Alzheimer disease (AD). Non-steroidal anti-inflammatory drugs may protect against both depression and AD, but observational studies have offered contradictory results. Present study evaluates the effects of anti-inflammatory diclofenac sodium (DS) on rat hepatic TDO and brain IDO activities. Adult Albino Wistar rats were divided into control and test groups, each test group received DS (2mg/kg) i.p. injection daily and were killed either after 3.5 hours (acute treatment) or after 3, 5 and 7 days (chronic treatment) while control groups received an equal volume of vehicle. Results show that TDO enzyme activity was inhibited and liver tryptophan concentrations were increased after 3 to 7 days treatment of DS; however no effect was seen on these parameters after 3.5hrs. Brain IDO activity was increased after both acute and chronic DS treatment. It is concluded that DS inhibits hepatic TDO enzyme activity following chronic treatment, while augments brain IDO activity following both acute and chronic DS treatment, this may result in rise in cerebral kynurenic acid and/or quinolinic acid concentrations. Therefore there is a need that effects of DS on kynurenine pathway should be further investigated to rule out the protective effect of DS in inflammation-induced depression and Alzheimer disease.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".