A Toxicologist's Guide to the Preclinical Assessment of Hepatic Microsomal Enzyme Induction

Abstract

The assessment of hepatic microsomal enzyme induction at the completion of preclinical toxicology studies in rodents and large mammals provides a wealth of information to the toxicologist and pharmacokineticist regarding how the drug-metabolizing system of the hepatocyte endoplasmic reticulum responded to high-dose levels of a xenobiotic designed for a specific pharmacological target in any of several target organs. The interpretation of these data can be greatly enhanced by a clear understanding of how this system functions and what the immediate and long-term ramifications are to organs and organ systems. This review focuses on how drugs modify the hepatic cytochrome P450 system, how those modifications are detected, the various consequences of these modifications, and some differences in the induction response among species.

Antioxidative stress effects of vitamins C, E, and B₁₂, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats

“… 2 The increase in ALT levels is more specific for liver damage than AST, since it is mainly found in the liver, whereas AST is also found in other tissues such as heart, skeletal muscles, kidney, red blood cells, and brain. 34 Intoxication of rats with APAP highly increased the levels of serum ALT and AST, indicating liver injury. However, pretreatment of rats with 500 mg/kg VC, 200 mg/kg VE, 10 mg/kg VB 12 , or their combination, daily for 8 days, significantly inhibited the increase of ALT serum levels; however, VC and the combination group significantly decreased AST serum levels unlike VE and VB 12 , which showed insignificant effect.…”