Formation of Biological Reactive Intermediates by Peroxidases: Halide Mediated Acetaminophen Oxidation and Cytotoxicity

Abstract

The physiological role of heme containing peroxidases in circulating or tissue infiltrating white cells, polymorphonuclear leukocytes, monocytes and eosinophils is to enable these cells to carry out their function of killing invading bacteria, viruses, parasites, protozoa, etc. or tumor cells. Another role is to inactivate regulators released into the blood stream such as estradiol, leukotrienes and chemotactic factors. The peroxidases in these cells are soluble but are located in granules or lysosomes. They are released into phagocytic vacuoles and/or from the cell when the cells are activated by invading microorganisms. Lactoperoxidase secreted into body fluids from the mammary gland, Zymbal gland, salivary gland, lacrimal gland and Harderian glands, etc may also play a role in killing invading organisms in body fluids. Peroxidases located in the rough endoplasmic reticular membrane and nuclear envelope of other cells are not released from the cell and are probably more concerned with the synthesis of regulators (eg. thyroxine by thyroid peroxidase, prostaglandin by prostaglandin synthetase) or the inactivation of regulators (eg. oestradiol by uterine peroxidase). The peroxidase of resident peritoneal macrophages or Kupffer cells of the liver are also located in the endoplasmic reticulum but are not discharged to phagocytic vacuoles so that their function may not be antimicrobial. Intestinal peroxidase and another uterine peroxidase have been attributed to infiltrated eosinophils whereas spleen peroxidase has been attributed to infiltrated monocytes (Banerjee, 1988). Peroxidases are therefore ubiquitous in tissues either as a result of endogenous activity or as a result of infiltrated white blood cells.