Author ORCID Identifier
https://orcid.org/0009-0004-0674-1798
Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Pharmacology & Toxicology
First Advisor
Hamid Akbarali
Second Advisor
Yuesheng Zhang
Third Advisor
Can Senkal
Abstract
Chronic opioid therapy is widely used for pain management but is frequently limited by gastrointestinal toxicity. Emerging evidence suggests that opioid-induced gut dysfunction contributes to systemic inflammatory changes that may exacerbate analgesic tolerance. The present study investigated the potential protective effects of broccoli seed extract (BSE), rich in the bioactive cytoprotective isothiocyanate sulforaphane, on chronic opioid-induced gastrointestinal dysfunction and associated antinociceptive tolerance. Both in vivo and in vitro experimental approaches were employed in this project. In vivo, mice were subjected to chronic morphine administration with or without co-treatment with BSE. Analgesic tolerance was assessed using tail immersion nociceptive assay following acute morphine challenge, including both single-dose and cumulative dose-response paradigms. Intestinal barrier integrity was evaluated using FITC-dextran permeability assays, while histological analysis of colon sections was performed using hematoxylin and eosin staining to assess structural alterations in epithelial architecture. To further investigate epithelial-specific inflammatory responses, an in vitro model was established using T84 intestinal epithelial cells treated with colon-conditioned medium derived from morphine-exposed animals. Interleukin-8 (IL-8) gene expression was quantified as a marker of epithelial inflammation. Additional mechanistic studies examined the effects of BSE under basal conditions and following inflammatory stimulation. Chronic morphine exposure induced significant antinociceptive tolerance, increased intestinal permeability, and disrupted colonic architecture. BSE co-administration demonstrated a modest modulatory effect in vivo, with attenuation of tolerance observed in dose-dependent analyses, although permeability changes were not statistically significant. In vitro, morphine colon-conditioned medium significantly increased IL-8 expression, which was effectively reversed by BSE pre-treatment under inflammatory conditions. Notably, BSE exhibited concentration-dependent effects on basal IL-8 expression, suggesting a biphasic biological response. Overall, these findings suggest that BSE exerts a modest but biologically relevant protective effect against opioid-induced gastrointestinal dysfunction and epithelial inflammation. The data support the hypothesis that modulation of gut epithelial homeostasis may contribute to altered opioid responsiveness, highlighting BSE as a potential adjunct therapeutic strategy warranting further mechanistic investigation.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-7-2026