Title page for ETD etd-04272010-221042


Type of Document Master's Thesis
Author Snow, Lynne A.
URN etd-04272010-221042
Title Carprofen-Induced Oxidative Stress in Mitochondria of the Colonic Mucosa of the Dog
Degree Master of Science (M.S.)
Department Veterinary Clinical Sciences
Advisory Committee
Advisor Name Title
McConnico, Rebecca Committee Chair
Davidson, Jacqueline Committee Member
Hosgood, Giselle Committee Member
Keywords
  • dinitrophenol
  • tempol
  • carprofen
  • oxidative stress
  • mitochondria
  • colon
  • DNP
Date of Defense 2010-03-15
Availability unrestricted
Abstract
Objectives

1) To measure conductance and permeability of canine colonic mucosa exposed to increasing concentrations of carprofen.

2) To compare conductance and permeability of canine colonic mucosa exposed to carprofen or 2,4-dinitrophenol (DNP) and tempol blockade.

Design

In vitro randomized block design

Animal

20 mixed breed dogs

Methods

Conductance, mannitol flux, and histology were evaluated in colonic mucosa mounted in Ussing chambers. Mucosa was first exposed to increasing concentrations of carprofen. Mucosa was then exposed to either carprofen (200 μg/ml) or DNP (0.25mM) +/- tempol (1mM) pretreatment. Conductance over time, mannitol fluxes, and frequency of histologic categories were analyzed for treatment effects. Histopathology and electron microscopy were evaluated post experiment.

Results

Mean +/- SEM conductance*time for 400 μg/ml carprofen treated colon was significantly greater than control. Mean +/- SEM conductance*time for carprofen treated colon at 200, 100 and 40 μg/ml were not significantly different from control. Mean +/- SEM conductance*time for 400 μg/ml and 200 μg/ml carprofen treated colon were not significantly different. Period 3 mannitol flux was greater than period 1 for 400 μg/ml and 200 μg/ml carprofen treated colon but not significantly different for 100 μg/ml, 40 μg/ml, and control. Period 3 flux for 400 μg/ml and 200 μg/ml carprofen treated colon were not different but were greater than control. Mean +/- SEM conductance*time for carprofen or DNP treated colon were not significantly different from control regardless of blockade. Period 3 flux for carprofen and DNP treated colon were not different but were greater than control. Period 3 flux for carprofen treated colon with tempol pretreatment was not significantly different than control. Period 3 flux for DNP treated colon with tempol pretreatment was not different than without tempol but was greater than control. Cell sloughing and erosions were observed with high carprofen concentrations. Mitochondrial damage was seen with carprofen treatment compared to DNP treatment or control. Tempol pretreatment effect on mitochondrial morphology was inconsistent.

Conclusion

Carprofen exhibits concentration dependent toxicity to canine colonic mucosa. Carprofen and DNP induce similar mucosal damage evident by changes in electrical conductance, mannitol flux, and histopathology. Carprofen damages enterocyte mitochondria.

Files
  Filename       Size       Approximate Download Time (Hours:Minutes:Seconds) 
 
 28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access 
  Snow_Thesis.pdf 2.44 Mb 00:11:17 00:05:48 00:05:04 00:02:32 00:00:13

Browse All Available ETDs by ( Author | Department )

If you have questions or technical problems, please Contact LSU-ETD Support.