Chronotolerance for cisplatin ototoxicity in the rat.
Level 5 - mechanism / opinion, no new human data
Preclinical animal experimental study
PubMed 30253329 · doi:10.1016/j.heares.2018.09.004
What was done
Fifty-seven Fischer 344/NHsd rats maintained on a 12-hour light/12-hour dark cycle received an intraperitoneal injection of cisplatin (12 mg/kg) at one of six time points: 2, 6, or 10 hours after light onset (inactive phase) or 2, 6, or 10 hours after light offset (active phase). Cochlear injury was assessed via auditory brainstem response threshold shifts and postmortem outer hair cell counts.
What was found
All animals showed threshold shifts at high frequencies (30 and 40 kHz). Rats treated 6 hours after light onset (inactive phase) had significantly higher mid-frequency threshold shifts and greater outer hair cell loss compared to rats treated during the dark hours. Exact numerical values and statistics were not reported in the abstract.
Why it matters
This study demonstrates that circadian timing modulates cisplatin ototoxicity in rodents, mirroring established patterns of chronotolerance for nephrotoxicity and providing a rationale for investigating chronotherapy in human cancer treatment.
Limits
The study was conducted in a nocturnal rodent model using intraperitoneal administration, which cannot be directly translated to diurnal human patients or clinical dosing protocols. The abstract provides no exact quantitative values, variance, or p-values, and it did not evaluate whether chronotolerance alters anti-tumor efficacy.
Cited by
- supports The inner ear possesses its own intrinsic circadian rhythm, which can influence the efficacy of certain drugs depending on the time of day they are administered.