Chemical modification of ascorbic acid to L-ascorbyl-6-palmitate: A novel approach for improved antioxidant therapy in traumatic brain injury

Oxidative stress, caused by an excessive amount of reactive oxygen species is a major factor in the pathophysiology of complications following traumatic brain injury (TBI). Ascorbic acid, a vital antioxidant, has been employed in TBI therapy, but its instability, limited bioavailability, rapid oxidation, and pro-oxidant effects pose significant limitations. To overcome these drawbacks, the ascorbic acid was chemically modified resulting in a fat-soluble L-ascorbyl-6-palmitate. The effects of L-ascorbyl-6-palmitate on oxidative stress biomarkers in TBI rats were subsequently evaluated. TBI was developed in rats by a weight drop method. The study involved five experimental groups: ascorbic acid group, L-ascorbyl-6palmitate group, dimethyl sulfoxide group, traumatized non-treated group, and non-traumatized non-treated control group. A total of twenty-five rats were used in the experiment, with five rats in each group (n=5). The levels of malondialdehyde and the activity of antioxidant enzymes such as glutathione peroxidase, catalase, and superoxide dismutase were assessed in serum and brain tissue samples. In both serum and brain tissue, ascorbic acid, L-ascorbyl-6-palmitate, and dimethyl sulfoxide showed significant (P<0.05) elevation in enzyme activities and reduction in malondialdehyde levels compared to the traumatized non-treated group. Additionally, L-ascorbyl-6-palmitate treatment demonstrated higher antioxidant potential and scavenging ability than ascorbic acid treatment, as evidenced by significantly (P<0.05) increased superoxide dismutase, catalase, and glutathione peroxidase activities, and reduced malondialdehyde levels. These findings demonstrate the neuroprotective effects of L-ascorbyl-6-palmitate in managing TBI-induced oxidative stress. Further studies should investigate the underlying molecular mechanisms and long-term effects of L-ascorbyl-6-palmitate treatment on neurological recovery and functional outcomes in TBI, as well as explore its potential synergistic effects with other antioxidants or neuroprotective strategies.