Fig. 1. (A) Serum alanine transaminase (ALT) activity at 1 h and 5 h following a single toxic i.p. injection of paracetamol in CD-1 mice with and without prazosin pre-treatment. Asterisks (*) show statistical difference between treatment groups (*p < 0.05). (B) Depletion of hepatic glutathione at 1 h and 5 h following a single toxic i.p. dose of paracetamol in CD-1 mice with or without prazosin pre-treatment. No statistical difference was observed between the two groups. Paracetamol (in saline) and prazosin (in corn oil) were administered at doses 530 mg/kg and 15 mg/kg, respectively. Open columns, 1 h, filled columns, 5 h.

Fig. 2. (A) Hepatic glucuronidation of a single i.p. injection of low dose (150 mg/kg) and high dose (530 mg/kg) APAP in CD-1 mice with and without prazosin pre-treatment. Animals in each treatment group (n = 6) were killed 1 h later and the livers removed, homogenized and differentially centrifuged before HPLC analysis. The levels of APAP-glucuronide were determined as described under Section 2. Data are presented as a percentage of the administered dose. Filled columns, with prazosin; open columns, without prazsoin. Asterisks (*) show statistical difference between prazosin-treated and non-prazosin treated animals (*p < 0.05). (B) Hepatic glutathione conjugation of APAP as a pecentage of the administered dose. (APAP-glucuronide and APAP-glutathione conjugate had retention times of 7.6 min and 8.8 min in the same HPLC run.) Filled columns, with prazosin; open columns, without prazsoin. No statistical difference was observed between the prazosin-treated and non-prazosin treated animals, (C) Michaelis–Menten kinetics curve for the glucuronidation of APAP by hepatic microsomes. Microsomes were prepared from animals (n = 8) administered a single i.p. injection of either controls (0.2 mL corn oil) or prazosin (15 mg/kg). The animals were killed 1 h later, livers removed and microsomes prepared and pooled for each group. The prepared microsomes were then incubated with a range of APAP concentrations (0.05–10 mM) and the rate of formation of APAP-glucuronide was determined as detailed under Section 2. Filled triangles, controls; filled squares, prazosin pre-treated, and the level of APAP-glucuronide was determined by HPLC. Data are presented as rate of formation of APAP-glucuronide versus [APAP] and show that there was no statistical difference between mean apparent K_m and V_max for microsomes prepared from the two groups.