The Effect of Delayed Systemically Administered n-Acetylcysteine on the Cochlear Oxidative State and on Cisplatin Induced Ototoxicity In Vivo in Guinea Pigs
Bibliographic record
Abstract
Cisplatin is an effective antineoplastic drug which is often limited in it‘s use by an ototoxic side effect. After cisplatin enters the cochlea, a large amount reactive oxygen species (ROS) is generated. This large production of ROS appears to overwhelm the cells’ mechanisms of ROS regulation and is thought to mediate damage to cells within the cochlea. Past studies have shown that the ototoxicity of cisplatin can be diminished when it is administered concurrently with an antioxidant such as n-acetylcysteine (NAC). It is thought that the mechanism of NAC’s action is through it’s ability to counteract the overwhelming ROS production. Unfortunately, a concern exists that the efficacy of cisplatin is reduced by the NAC when the two agents are administered concurrently. Our study was designed to circumvent this concern by administering NAC long after the cisplatin treatments have ended. Thus we could determine if the delayed administration of NAC could reverse the ototoxic effect of cisplatin, possibly without affecting the efficacy of cisplatin. In our study, guinea pigs were administered a course of cisplatin treatments. NAC was then administered 30 days after the completion of the cisplatin treatments. Auditory brainstem responses were used to determine hearing loss. A redox probe was used to measure the intracochlear oxidative states in vivo. NAC did not reverse the ototoxicity of cisplatin and was found to not change the intracochlear oxidative state. The results of this study suggest the possibility of a tolerance to the effect of systemically administered antioxidants.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".