Impact of Mild Traumatic Brain Injury (Mtbi) on Cyp2d6 Activity and the Restorative Effects of Melatonin and Vitamin C Supplementation Publisher



Berenjian K ; Gholipour Z ; Khoshayand M ; Sharifzadeh M ; Rouini M ; Ardakani YH
Source: Iranian Journal of Pharmaceutical Research Published:2027

Abstract

Background: Mild traumatic brain injury (mTBI) may disrupt hepatic cytochrome P-450 enzyme activity, potentially altering drug pharmacokinetics. Objectives: This study investigated the impact of mTBI on CYP2D6 activity and the restorative effects of melatonin and vitamin C supplementation. Methods: Mild traumatic brain injury was induced in rats using a modified weight-drop model, which were then assigned to treatment or control groups. CYP2D6 activity was assessed at multiple time points post-injury using metabolic ratios of tramadol and mirtazapine through isolated liver perfusion. All experimental procedures were conducted with the investigator blinded to group assignments. Results: Mild traumatic brain injury significantly suppressed CYP2D6 activity on day 3, with partial recovery by day 7. While tramadol metabolism normalized by day 28, mirtazapine metabolism remained impaired in non-supplemented groups. Supplementation accelerated CYP2D6 recovery, showing statistically significant change by day 7. By day 28, supplemented groups exhibited metabolic ratios surpassing baseline levels. Conclusions: Mild traumatic brain injury induces transient suppression of CYP2D6 activity, which was attenuated in antioxidant-treated groups in this preclinical model. Further studies are needed to explore the clinical relevance of these findings. Copyright © 2026, Berenjian et al.