Intracellular antioxidants and

Glutathione, an intracellular antioxidant, and why too much acetaminophen is toxic... 

Figure 9.2. Mechanisms of aminoglycoside toxicity. This schematic representation summarizes the principles of aminoglycoside toxicity discussed in the text. Treatment with the drugs leads to the formation of reactive oxygen species through a redox-active complex with iron and unsaturated fatty acid or by triggering superoxide production by way of NADPH oxidase. An excess of reactive oxygen species, not balanced by intracellular antioxidant systems, will cause an oxidative imbalance potentially severe enough to initiate cell death pathways. Augmenting cellular defenses by antioxidant therapy can reverse the imbalance and restore homeostasis to protect the cell.

Figure 27.12. Lung intracellular antioxidant enzyme systems. The three major systems Superoxide dismutase, catalase, and the glutathione redox cycle are shown. (See text for details.)...

Superoxide dismutase The major intracellular antioxidant enzyme in aerobic cells, the Cu-Zn form in the cytoplasm and the manganese form in the mitochondria, reduces superoxide radicals to hydrogen peroxide very rapidly and specifically. 

N-acetylcysteine, a precursor of glutathione, which is a natural intracellular antioxidant, has been tested in a randomized, placebo controlled trial in patients with ALS. Thirty-five patients (65%) given N-acetylcysteine 50mg/kg subcutaneous infusion daily and 30 patients (54%) given placebo were still alive at 12 months, a difference that was not statistically significant (Louwerse et al., 1995). 

Ascorbic acid is required for the synthesis of collagen. It is also a powerful reducing agent (antioxidant) and plays a part in intracellular oxidation-reduction systems, and in mopping up oxidants (free radicals) produced endogenously or in the environment, e.g. cigarette smoke (see Vitamin E). 

As mentioned, ROS generated by cells recruited to the site of inflammation, are a major cause of oxidative stress and ensuing cell damage. When ROS production increases, the redox balance alters, being GSH, along with the regulatory machinery, the major intracellular antioxidant. 

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