Melanin

Melanin also forms stable free radicals, quenches excited states, and binds radical-forming agents such as transition-series metals. All likely contribute to its putative role in antioxidant defense. On the other hand, the ability of melanin to bind toxic radical-generating agents may sometimes be detrimental, as in chloroquine retinopathy and aminoglycoside ototoxicity (41). Finally, melanin can function as an efficient S0Dase and may retain this function in pigmented organs. Thus, the melanins ( which can form abiologically ) may be the oldest evolved system for defense against oxygen radicals, rather than SOD/catalase.

Free radicals are produced by environmental causes such as light or ionizing radiation. However, three physiological processes can result in extraordinarily high levels of radical species. These include the mixed-function oxidase system of endoplasmic reticulum, the NADPH oxidase system of inflammatory cells, and the presence of high levels of autoxidation-mediating charge-transfer agents. Production of activated species by such mechanisms can exceed the capacity of local protective mechanisms and produce tissue injury.

Inflammatory cells produce active species of oxygen in antimicrobial defense (1,2). While such species may directly damage surrounding tissues, their major secondary role may be to mediate important components of the inflammatory response. For example, Figure 3 lists some of the inflammatory immunomodulators reported to be affected in vitro by one or more components of the active oxygen system. Inflammation in the general sense comprises the whole of the systemic response to injury, so many of these same processes may also occur in ischemic injury, for example. While circumstantial, the list includes most of the major components of the inflammatory response and grows daily.

Similarly, antioxidants, SOD, and catalase have significant anti-inflammatory properties (3-5). For example, Orgotein, the pharmaceutical preparation of SOD, is used in veterinary medicine. It is reported to be both safe and effective in the treatment of various inflammatory and degenerative lesions in man ( 3-4 ). The action of many other antiinflamatory drugs may also involve interactions with the active oxygen system.4 Such agents may act by interfering with the action of phagocyte-produced active oxygen species on one or more of the systems outlined in Figure 3. The role of active species in the inflammatory response may also explain the dermal pigmentary response in inflammation (4). Active oxygen species may also have a role in endotoxin shock, burn-induced plasma volume loss, and even in atherosclerosis - e.g., the atherosclerotic lesions in homocystinuria. Likewise, radical mechanisms may play a role in stroke, cerebral edema, and spinal cord injury, as well as ischemic injury ( 42 ).