Reactive oxygen species cellular production

Figure 14. Schematic of reactive oxygen species production and cellular defense mechanisms (antioxidant enzymes catalase, SOD, GSH). Reactive oxygen species (ROS) production is detrimental for the cell. However, ROS, in small amounts and for short periods, can act as intermediates of cardioprotective signaling.

Balsam fir oil was active against all tumor cell lines with GI50 values ranging from 0.76 to 1.7 mg/mL. After GC-MS analysis among the monoterpenes found (about 96%) a-humulene proved itself to be responsible for cytotoxicity (GI50 55 pM). Both the EO and a-humulene induced a dose- and time-dependent decrease in cellular glutathione (GSH) content and an increase in reactive oxygen species (ROS) production. 

The antioxidant system in humans is a complex network composed by several enzymatic and nonenzymatic antioxidants. In addition to being an antioxidant, lycopene also exerts indirect antioxidant properties by inducing the production of cellular enzymes such as superoxide dismutase, glutathione S-transferase, and quinone reductase that also protect cells from reactive oxygen species and other electrophilic molecules (Goo and others 2007). 

All aerobic organisms contain substances that help prevent injury mediated by free radicals, and these include antioxidants such as a-tocopherol and the enzymes superoxide dismutase and glutathione peroxidase. When the protective effect of the antioxidants is overwhelmed by the production of reactive oxygen species, the intracellular milieu becomes oxidative, leading to a state known as oxidative stress (Halliwell and Gutteridge, 1999). Thus the balance between the generated free radicals and the efficiency of the protective antioxidant system determines the extent of cellular damage. 

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.

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