alexa Delayed calcium channel blockade with diltiazem reduces paracetamol hepatotoxicity in mice.


Journal of Drug Metabolism & Toxicology

Author(s): Deakin CD, Gove CD, Fagan EA, Tredger JM, Williams R

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Abstract 1. Diltiazem (30 mg kg-1 body weight, intraperitoneally) given to mice 9 h after paracetamol (450 mg kg-1, orally) reduced liver damage, as judged by plasma aspartate aminotransferase activity (median 186, range 6-602 IU 1(-1), n = 18 vs 466, range 23-3872 IU 1(-1) in 18 saline-treated controls; P less than 0.05) with comparable reductions in mortality (14\% vs 33\%, respectively; NS). 2. Regenerative activity, as judged by mitotic figures in tissue removed at 30 h after paracetamol, was significantly higher in mice treated at 9 h with diltiazem (median 0.83 per high power field vs 0.1 in saline-treated controls; P less than 0.05). 3. Diltiazem administered earlier or later than 9 h showed reduced efficacy and in some cases potentiated toxicity, as did nifedipine (40 mg kg-1 in divided doses up to 9 h).
This article was published in Hum Exp Toxicol and referenced in Journal of Drug Metabolism & Toxicology

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