Abstract
Background: The mucus layer covering the intestinal epithelium is the front line of defense against invading pathogens and foreign antigens. The layer is largely comprised of mucins, the secretory products of intestinal goblet cells. Thus, goblet cells play an essential role in maintaining intestinal homeostasis and barrier function. Alterations in the number and function of goblet cells and dysregulation of intestinal mucus have been reported in response to luminal insults including in the modulation of gut microbiota to cause intestinal inflammation. Furthermore, opioid administration has been shown to lead to dysregulated immune responses, increased intestinal barrier permeability, bacterial translocation, and altered microbial composition. In this context, we are interested in evaluating the impact of oxycodone intoxication and withdrawal on intestinal goblet cells in an adolescent rat model.
Materials and Methods: A repeated, passive injection model was used in male and female adolescent rats to initiate oxycodone intoxication and withdrawal. Rats were injected with increasing oxycodone concentrations (0, 0.5, 1, 3, to 5 mg/kg body weight every 12 hours). In one experimental group, withdrawal was precipitated at the end of the 6-day injection paradigm with an intraperitoneal injection of naloxone (1 mg/kg) two hours after oxycodone administration. Subsequently, withdrawal behavior was monitored. In control groups, saline instead of drug injections were used. For histological evaluation, about 8 cm long sections of the proximal small intestine were preserved in Methacarn fixative until processing. For goblet cell quantification, tissue sections stained with Alcian Blue/ Periodic acid Schiff-stain were used. Microscopic images were used for goblet cell quantification.
Results: The number of goblet cells per epithelial cells in small intestine villi in both male and female rats decreased significantly after oxycodone and oxycodone/naloxone treatments compared to controls. However, no differences in goblet cell percentages were found between male and female rats. Our results suggest that chronic oxycodone administration can reduce goblet cell numbers and thereby disrupt gut homeostasis, which could lead to intestinal inflammation.
Conclusion: This study provides further insights into the disruption of intestinal homeostasis by oxycodone misuse.
Materials and Methods: A repeated, passive injection model was used in male and female adolescent rats to initiate oxycodone intoxication and withdrawal. Rats were injected with increasing oxycodone concentrations (0, 0.5, 1, 3, to 5 mg/kg body weight every 12 hours). In one experimental group, withdrawal was precipitated at the end of the 6-day injection paradigm with an intraperitoneal injection of naloxone (1 mg/kg) two hours after oxycodone administration. Subsequently, withdrawal behavior was monitored. In control groups, saline instead of drug injections were used. For histological evaluation, about 8 cm long sections of the proximal small intestine were preserved in Methacarn fixative until processing. For goblet cell quantification, tissue sections stained with Alcian Blue/ Periodic acid Schiff-stain were used. Microscopic images were used for goblet cell quantification.
Results: The number of goblet cells per epithelial cells in small intestine villi in both male and female rats decreased significantly after oxycodone and oxycodone/naloxone treatments compared to controls. However, no differences in goblet cell percentages were found between male and female rats. Our results suggest that chronic oxycodone administration can reduce goblet cell numbers and thereby disrupt gut homeostasis, which could lead to intestinal inflammation.
Conclusion: This study provides further insights into the disruption of intestinal homeostasis by oxycodone misuse.
| Original language | American English |
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| State | Published - 21 Jul 2023 |
| Event | 7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics - Tandy Conference Center, Tulsa, United States Duration: 21 Jul 2023 → 21 Jul 2023 |
Conference
| Conference | 7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics |
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| Abbreviated title | 7th Joint Annual Research Meeting |
| Country/Territory | United States |
| City | Tulsa |
| Period | 21/07/23 → 21/07/23 |