الفهرس 
Liver and thyroid dysfunctionOnly 14 pages are availabe for public view
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Abstract
The present study was undertaken to investigate the acute and chronic hepatotoxic effects of paracetamol in rats with thyroid dysfunctions, as well as to evaluate the protective role of the synthetic sulfhydryl compound; 2-mercaptopropionylglycine in management of the adverse effects ensuing paracetamol administration to the rats. Albino rats, Rattus rattus norvenicus, with either experimentallyinduced hyper-or hypothyroid states, in addition to normal euthyroid animals were used throughout this study. The toxicity of paracetamol in thyroid rats was monitored by determination of the LD50 of the drug for each thyroid state. At the subjective level and for each thyroid state, the acute and chronic hepatotoxic effects were determined in paracetamol over-dosed animlas where at the acute level, rats were given an intraperitoneal dose equivalent to its minimal lethal dose deduced from the respective LD50 curve while at the chronic level , rats were given up to 20 doses each of size equivalent to 1110 of its LD50. However, for assessment of the protective role of 2-MPG in management of paracetamol hepatotoxicity in each thyroid state, both acute and chronic overdosed animals were given single dose of 2-MPG (1 00 mg / kg for acute and 50 mg /kg for chronic prior each paracetamol injection. However the severity of both acute and chronic paracetamol toxicity in the liver as well as the protective role of 2-MPG were subjectively monitored by biochemical analytical criteria indicative of liver injury including liver glutathione and serum albumin levels, enzyme profile and liver lipid pattern; total lipids and triglycerides as well as by the conventional histopathological technique.At the objective level, the reflection of both the severity of paracetamol toxicity and the potency of 2-MPG in management of such toxicity on the status of over-dosed rats were determined by monitoring of the survival curves of animals given minimal lethal dose of paracetamol with or without 2-MPG. The data obtained showed the following: 1. The LD,, of paracetamol varies with the activity of the thyroid function where its magnitude decreased as the thyroid activity increased.For normal euthyroid rats, the LD,, was found to be 758.12 mglkg while for hyperthyroid animals it displayed a value of 493.26 mg /kg which is far lower than that recorded for hypothyroid animlas and amounted to 99 1.49 mgkg. 2. As for the hepatotoxic effects of paracetamol, it was found that the drug caused marked functional disorder and histological degenerative changes in the liver. In norrnal euthyroid rats, acute paracetamol administration caused significant hepatic dysfunction as manifested/ by decreased liver enzymatic activities of arginase and 5-nucleotidase with concomitant elevation of transaminases levels in serum, in addition to depleted glutathione and serum albumin levels. Liver content of both total lipids and triglycerides was found to be decreased. Though showed slight limited tendency to recovery, these functional changes were still seen up to 48 hr after paracetamol administration. Also, chronic paracetamol administration caused marked functional and more persistent hepatic disorder as apparently manifested by increased total lipid and triglyceride contents of the liver, besides depleted liver glutathione content and serum albumin level. As for the degenerative changes brought about by paracetamol in the liver, mainly the hepatocytes appeared to be affected and both the extent and degree of injury was found to be more severe in chronic than in acute paracetamol administration and is characterized by liver cell pale-staining-focal necrosis which was usually centrilobular and midzonal. Congestion of the central hepatic vein was observed with local haemorrhage and polymorphonuclear infiltration around. 3. Both functional disorder and histopathological changes were found to be %more severe in hyperthyroid than in normal euthyroid rats whereas hypothyroid rats displayed the least changes. This could be attributed to the increased metabolic bioactivation of paracetamol to a more toxic metabolite.