Oxidative Stress in Intervertebral Disc Degeneration
Oxidative stress is the presence of a damaging level of oxidative molecules, more than cells can cope with without resulting in harmfully altered behavior, dysfunction, cell death, and so forth. Increased levels of oxidative molecules is a feature of aging and inflamed tissue. As researchers here note, it appears in the context of degenerative disc disease. Targeting oxidative stress with antioxidant compounds has achieved some success for some conditions of local inflammation, such as the use of mitochondrially targeted antioxidants for uveitis, but the fine details of how a specific antioxidant interacts with cellular machinery matters greatly. A range of antioxidants have been tested in animal models for the treatment of degenerative disc disease, but little of this has progressed into human trials.
Intervertebral disc degeneration (IDD) is caused by aging, long-term sitting, long-term spinal load, and other factors. At the same time smoking, diet, and other factors can also lead to IDD. Abnormal accumulation of reactive oxygen species (ROS) occurs within the intervertebral disc, causing the production-clearance homeostasis to be disrupted, and excess ROS leads to activation of pathways downstream of ROS, which in turn triggers a range of symptoms.
When IDD occurs, the disc system undergoes intense, localized oxidative stress. From a molecular perspective, superoxide dismutase activity is significantly reduced in the plasma of IDD patients or rats, and levels of various biomarkers of oxidative stress, including phospholipase A, fructosamine, malondialdehyde, peroxide potential, total hydrogen peroxide, advanced oxidation protein products and NO, induce DNA damage, lipid metabolism, and protein synthesis disorder. From the cellular perspective, oxidative stress promotes the degeneration of normal nucleus pulposus cells in the IVD microenvironment, and impedes the function of collagen-secreting cells.
From a more macroscopic point of view, the degeneration of nucleus pulposus cells results in the decrease of type II collagen content, which is replaced by type I collagen. The annulus fibrosus is impacted by external force, and its effect of dispersing and relieving stress is weakened, which makes the annulus fibrosus easier to break, and causes the nucleus pulposus to expand and compress the nerve, resulting in more clinical symptoms.