Role of thiols in protection against biological reactive intermediates.

Abstract

Thanks to the pioneering work of Elizabeth and James Miller1 it is now well established that the cytotoxic and carcinogenic effects of a wide variety of chemicals are mediated by reactive products formed during their biotransformation in the organism. It is equally clear that there exist a number of protective systems which can trap, or inactivate, toxic metabolites and thereby prevent their accumulation within the tissues and subsequent toxic effects. Although phase I reactions, in particular those mediated by the cytochrome P-450-linked monooxygenase system, are most often responsible for the production of toxic metabolites, there are now many examples of metabolic activation via phase II reactions, despite the fact that the latter normally serve a protective function. Hence, it is obvious that the formation of toxic metabolites cannot be attributed to any single enzyme or enzyme system, and that the balance between metabolic activation and inactivation is absolutely critical in deciding whether exposure to a potentially toxic compound will result in toxicity, or not.