Optimization of the dose and route of injection, and characterisation of the time course of carbon tetrachloride-induced hepatotoxicity in the rat.
BACKGROUND
The purpose of this study was to optimize carbon tetrachloride-induced hepatotoxicity in the rat with respect to dose, route of injection, and time course.


METHODS
Male Wistar albino rats, 4 to 6 weeks old and weighing 130-180 g were used. Hepatotoxicity was evaluated by measuring the activity of serum enzymes (alkaline phosphatase [ALP], alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) as well as serum total bilirubin level.


RESULTS
Intraperitoneal injection of carbon tetrachloride (CCl(4)) increased the activity of ALP (from 64.9 to 137.3 U/l), ALT (from 106.6 to 693.1 U/l), and AST (from 113.8 to 693.9 U/l). Plasma bilirubin level increased (from 0.119 to 0.42 mg/dl). In contrast, subcutaneous injection of CCl(4) had no effect on these variables. The optimum intraperitoneal dose of CCl(4) was found to be 2 ml/kg body weight (dissolved in an equal volume of olive oil), and this increased the level of bilirubin and the activity of the three enzymes significantly, without causing death of the animals. Hepatotoxicity was observed within 2 h of intraperitoneal injection of CCl(4) and reached a peak after 24 h. Bilirubin level and serum enzyme activities declined gradually to normal levels by 3 days after CCl(4) injection.


CONCLUSIONS
It is possible to reliably evoke reversible hepatotoxicity in rats by intraperitoneal injection of 2 ml/kg CCl(4).
Department of Nutrition and Food Technology, Jordan University of Science and Technology, P.O. Box 3030, Irbid, Jordan. jana@nust.edu.jo
Sana
S
Janakat
Hela
H
Al-Merie
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008111:Liver Function Tests; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar
D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin