Impact of Mild Traumatic Brain Injury (mTBI) on CYP2D6 Activity and the Restorative Effects of Melatonin and Vitamin C Supplementation

AuthorKaveh Berenjianen
AuthorZiba Gholipouren
AuthorMohammadreza Khoshayanden
AuthorMohammad Sharifzadehen
AuthorMohammadreza Rouinien
AuthorYalda Hosseinzadeh Ardakanien
Issued Date2026-12-31en
AbstractBackground: 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.en
DOIhttps://doi.org/10.5812/ijpr-164903en
URIhttps://brieflands.com/journals/ijpr/articles/164903en
KeywordMild Traumatic Brain Injuryen
KeywordCytochrome P-450 2D6en
KeywordMetabolic Ratioen
KeywordMelatoninen
KeywordVitamin Cen
KeywordPharmacokineticsen
PublisherBrieflandsen
TitleImpact of Mild Traumatic Brain Injury (mTBI) on CYP2D6 Activity and the Restorative Effects of Melatonin and Vitamin C Supplementationen
TypeResearch Articleen

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