Key Points
- To evaluate the protective effect of n-acetylcysteine against doxorubicin-induced cardiac toxicity in mice.
- CDF1 mice were pretreated with n-acetyl-l-cysteine before doxorubicin administration.
- Lethality, long-term mortality, and body weight changes were measured after doxorubicin treatment.
- Cardiac nonprotein sulfhydryl content was assessed post-treatment.
- Lethality decreased from 100% to 37.7% with n-acetylcysteine pretreatment (P<0.001).
- 51.4% survival was observed post multiple doxorubicin doses with n-acetylcysteine versus 16.7% in controls (P<0.01).
- Doxorubicin-related weight loss diminished by 55.2% for body weight and 60.9% for heart weight with n-acetylcysteine (P<0.05, P<0.02 respectively).
Structured PICO
Does n-acetylcysteine prevent doxorubicin-induced mortality and cardiac toxicity in mice?
PPopulationMale CDF1 mice, 6 weeks of maturation, including models implanted with P388 leukemia cells.
IInterventionN-acetyl-l-cysteine (NAC) 2,000 mg/kg administered via gastric intubation or intraperitoneal injection 1 hour before doxorubicin (single dose 20 mg/kg i.p. or multiple doses 5 mg/kg i.p. at 2-week intervals).
CComparatorEquivolume dosages of physiologic saline administered before doxorubicin.
OOutcomeSurvival/lethality at 56 days (single dose experiment) or 10 weeks after the final dose (multiple dose experiment).hard clinical
N-acetylcysteine pretreatment significantly reduces doxorubicin-induced mortality and cardiac toxicity in mice by increasing cardiac nonprotein sulfhydryl content, without altering doxorubicin's antineoplastic activity.