Malik, R.; Khan, K.; Hodgson, H.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA104
Academic Journal
Background: We characterised the clinical, biochemical, metabolic, and histological pattern of thioacetamide induced (TAA) hepatic failure in the rat, to create a model of substantial severity (60% mortality), which fulfils the criteria of reproducibility, reversibility, and the provision of a therapeutic window. The animals (n = 20) received two intra-peritoneal injections of TAA 8 hours apart and developed Grade 1/11 encephalopathy by 24 hours, followed by grade 111/1V encephalopathy at 48 hours. Overall the mortality over 96 hours was 60%. There was a persistent elevation in serum ALT levels from 24 hours (> 2000 iu/ml cf < 100 iu/ml in normal rats). There was a peak in serum ammonia levels seen at 48 hours (196 ± 33 iu/ml cf 54 ± 9 in normal rats). The histological sections at postmortem showed evidence of centrilobular hepatocellular necrosis. Previous studies administered primary mitogens prior to or at the time of necrogenicliver injury and have therefore not provided appropriate models of clinical scenarios. Aim: To characterise the effects of the primary mitogen, tri-iodothyonine (T[sub 3]) on cell proliferation within the liver, when administered following thioacetamide induced liver injury. Method: Two groups of rats received two intra-peritonea (IP) injections of thioacetamide (500 mg/kg) 8 hours apart. The first group received a subcutaneous injection of T[sub 3] (4 mg/kg) 12 hours after the second thioacetamide injection and the second group received vehicle only. The animals were sacrificed 24 hours after the T3 or vehicle was administered. An IP injection (50 mg/kg) of 5-bromo-2-deoxyuridine (brdU) was given to all rats one hour prior to sacrifice. Results: Both groups followed a similar clinical, biochemical course with no difference in ALT between groups at sacrifice (> 2000 iu/ml). H & E staining: there was an equivalent degree of centriIobular necrosis in both groups. Cell proliferation index: the BrdU index was greater in...


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