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Delayed Calcium Channel Blockade with Diltiazem Reduces Paracetamol Hepatotoxicity in MiceThe Institute of Liver Studies, King's College Hospital and School of Medicine and Dentistry, Denmark Hill, London SE5 8RX, UK
The Institute of Liver Studies, King's College Hospital and School of Medicine and Dentistry, Denmark Hill, London SE5 8RX, UK
The Institute of Liver Studies, King's College Hospital and School of Medicine and Dentistry, Denmark Hill, London SE5 8RX, UK
The Institute of Liver Studies, King's College Hospital and School of Medicine and Dentistry, Denmark Hill, London SE5 8RX, UK
The Institute of Liver Studies, King's College Hospital and School of Medicine and Dentistry, Denmark Hill, London SE5 8RX, UK 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 I-1, n = 18 vs 466, range 23-3872 IU I-1 in 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-1 in divided doses up to 9 h).
Human & Experimental Toxicology, Vol. 10, No. 2,
119-123 (1991) |
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