الفهرس 
Introduction
ParacetamolOnly 14 pages are availabe for public view
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Abstract
Acetaminophen is an extensively used analgesic drug worldwide and, although the drug is safe when used at therapeutic doses, is associated with significant morbidity and mortality when taken in overdose, particularly in individuals with preexisting liver disease.
After normal therapeutic doses, the low concentrations of NAPQI formed are readily detoxified by reaction with reduced glutathione (GSH).However, under conditions of overdose, rapid GSH depletion and a significant elevation in the levels of NAPQI occur, resulting oxidative stress, cell damage.
Argininosuccinate synthetase (ASS) is an important enzyme for the synthesis of arginine, as it catalyzes the reaction of citrulline and aspartate to form argininosuccinate which can then be broken down to arginine and fumurate. As a result, ASS is a critical enzyme in several metabolic processes requiring this arginine.
The current study was conducted to evaluate the efficacy of ASS as an early predictor for paracetamol-induced hepatic damage. In addition, asses the sensitivity and specifity of ASS as an early predictor of APAP induced hepatic damage in comparison with other traditional liver function and histopathology.
This work was done in the in laboratories of the department of Forensic Medicine and Clinical Toxicology, Pathology department, Faculty of Medicine, Minia University and laboratory of Clinical Pathology department, Minia University Hospital during the period from May 1st to June 30th 2017.
Sixty albino rats of both sexes with average weight 200-250 grams were included in this study. The rats were divided into six groups (each group contain 10 rats). group I was the control group, rats were received saline by oral route. from group II to group VI, rats were received 300mg/kg paracetamol by intra peritoneal injection and they sacrificed after 2 hours in group II, after 4hours in group III, after 12hours in group IV, after 24ourhs in group V and after 48hours in group VI. Liver was carefully dissected and prepared for histological examination.
The results revealed that paracetamol level started to increase from 2 hours post injection to reach its peak level at 4 hours post injection then decreased 12 hours, 24 hours and 48 hours post injection. Regarding liver enzymes, study has been found that there was a significant increase in ALT after 4 hours of ingestion and reach to peak at 24 hour post injection while, AST started to increase 4 hours post injection and reached to its peak after 12 hours post injection.
As regards the albumin level, a significant decrement 12 hours, 24 hours and 48hours post injection in comparison to control, 2 hours and 4 hours post injection. According to total bilirubin level, there is significant statistical increase after 4 hours and 48 hours post injection.
Regarding the effect of paracetamol on coagulation profile, the present study showed significant statistical increase in Prothrombin time at all estimated periods started from 4 hours of injection. On the other hand Prothrombin concentrations decreased after 24 hours post injection. The level of INR showed a significant increase after 24 hours and 48 hours compared with control, 2 hours, 4 hours and 12 hours groups.