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High altitude hypoxic stress results in increased production of reactive oxygen species (ROS) that damages lipids in the cell membrane, and proteins and DNA within the cell. Cells have a battery of antioxidative enzymes and non-enzymatic mechanisms to counterbalance these oxidative stress damages. This includes defense through reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPX), and catalase (CAT). Apart from this, a ubiquitous protein named Heme Oxygenase I has been shown to profoundly induce various stress stimuli. These enzymes play a substantial role in helping the plant adapt to stress conditions. The protective effect of Heme Oxygenase-I modulation on severe and acute hypobaric hypoxic insults induced oxidative stress biomarkers in rat models was explored.