| dc.description.abstract | Oxidative stress is the imbalance between prooxidants and antioxidants within a cell that can cause and/or contribute to the progression of many pathological conditions. Reactive oxygen species (ROS) formed from the metabolism of hydrogen peroxide (H2O2) or paraquat (PQ) can damage DNA, proteins, and polyunsaturated fatty acids (PUFAs). A cell’s ability to defend against oxidative stress depends on multiple factors including genetic make-up, subcellular organelle function and environmental factors. Lipoic acid (LA) is an antioxidant with high reactivity to free radicals, but because of its low redox potential, it is also known to regenerate ascorbic acid and -tocopherol, elevate intracellular glutathione (GSH) levels and modulate transcription factor activity. We used A549 lung epithelial cells in an in vitro model to study the mechanism(s) of LA effects against H2O2- and PQ-induced oxidative injury. We observed that LA was incapable of protecting against H2O2 toxicity; thus, we used PQ as the agent to induce oxidant-induced damage. Challenge of cells with PQ resulted in decreases of cell viability and mitochondrial membrane potential and increases in DNA fragmentation and intracellular Ca2+ levels. Challenge of cells with LA resulted in an increase in cell viability, but a decrease in mitochondrial membrane potential. Interestingly, LA pretreatment of PQ-challenged cells resulted in the potentiation of DNA fragmentation and intracellular Ca2+ levels. Our results indicate that LA enhanced the PQ-induced oxidative injury in A549 lung epithelial cells, perhaps by acting as a prooxidant. | en_US |
