Correlations between common tests for assessment of liver damage: Indices of the hepatoprotective activity of promethazine in carbon tetrachloride hepatotoxicity
✍ Scribed by Colin J. Reddrop; Kevin H. Cheeseman; T. F. Slater
- Publisher
- John Wiley and Sons
- Year
- 1983
- Tongue
- English
- Weight
- 962 KB
- Volume
- 1
- Category
- Article
- ISSN
- 0263-6484
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✦ Synopsis
The effects of promethazine (PM) on different aspects o f the hepatotoxic action o f CC14 in the rat were investigated with the objective of finding rapid and reliable indicators of hepatoprotective effects. The study was based on definitive histdogical assessment o f liver damage caused by CC14 in the presence and absence of PM: PM (78 pmol kg-I, i.p.) protected against CC14-induced hepatic necrosis 24 h after a low dose of CCI, (1.3 mmol kg-') but not against G higher dose (13.0 mmol kg-I). The large increases in plasma activities of GOT, GPT and LDH produced by dosing with CCI, were partially inhibited by the administration o f PM. PM and CC14 caused a synergistic and long-lasting decrease in body temperature (2-3'C for 8-10 h). Modifying the toxicity with PM, together with a low dose of CC14 helped to minimize secondary effects of CC14 to clarify the sequence of toxic events, and to assess the sensitivity of some standard tests of hepatotoxicity. Simultaneous measurement of over 20 commonly used biochemical screening tests in individual animals 3 or 6 h after treatment permitted direct correlation of a wide variety of concentrations, activities and effects. For example, liver CHC13 concentrations (as a measure of CC14 metabolism) correlate strongly with increases in diene conjugation of microsomal lipids (as a measure of CCI,-induced lipid peroxidation); malonaldehyde production appears to be less sensitive as a measure of lipid peroxidation in vivo than diene conjugation. The changes induced in each parameter and the correlations between them are discussed with reference to the overall nature of the hepatotoxic reaction and its modification by PM.