Delayed Calcium Channel Blockade with Diltiazem Reduces Paracetamol Hepatotoxicity in Mice

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Abstract
1 Diltiazem (30 mg kg-1body 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 I-1, n = 18 vs 466, range 23-3872 IU I-1in 18 saline-treated controls; P < 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 < 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-1in divided doses up to 9 h).