Mitigation of pennyroyal hepatotoxicity in the mouse

Background: Pennyroyal oil ingestion has been associated with severe hepatotoxicity and death. The primary constituent, pulegone, is metabolized via hepatic cytochrome P450 to toxic intermediates. The purpose of this preliminary study was to assess the ability of the specific CYP450 inhibitors disulfiram and cimetidine to mitigate hepatotoxicity in mice exposed to toxic levels of pulegone. Methods: 20 gm female BALB/c mice were pretreated either with cimetidine 150 mg/kg ip, disulfiram 100 mg/kg ip, or both. After one hour, mice were administered pulegone 300 mg/kg ip, and sacrificed 24 hours later. Data were analyzed using one-way ANOVA. Post-hoc t-tests used Bonferroni correction. 95% CI refers to the 95% confidence intervals of the difference of the mean from pulegone (* = p < 0.05) (see table). Conclusions: At present, no specific therapy for pennyroyal toxicity exists. The current data suggest that within the limitations of a pretreatment animal model, the combination of cimetidine and disulfiram significantly mitigate the effects of pennyroyal toxicity. Experimental Group Mean SGPT (IU/L) Std Error No treatment 27.0 2.3 Pulegone 182.0 50.7 Disulfiram + Pulegone 93.3 18.9 Cimetidine + Pulegone 71.2 5.6 Disulfiram + Cimetidine + Pulegone 64.0 7.3 Experimental Group 95% CI No treatment Pulegone Disulfiram + Pulegone -12.8-190.3 Cimetidine + Pulegone 6.9-214.7 * Disulfiram + Cimetidine + Pulegone 14.1-221.9 * Abstract 225. Sztajnkrycer MD (1,2), Otten EJ (1,2), Bond GR (1,2), Lindsell CJ (3), Goetz RJ. (1) (1) Cincinnati Drug and Poison Information Center, (2) Department of Emergency Medicine, (3) Institute for Health Policy and Health Service Research, University of Cincinnati, Cincinnati, OH
Sztajnkrycer MD (1,2), Otten EJ (1,2), Bond GR (1,2), Lindsell CJ (3), Goetz RJ. (1) (1) Cincinnati Drug and Poison Information Center, (2) Department of Emergency Medicine, (3) Institute for [...]