Ossabaw Pig Demonstrates Detrusor Fibrosis and Detrusor Underactivity Associated
with Oxidative Stress in Metabolic Syndrome.
Authors Powell CR, Kim A, Roth J, Byrd JP, Mohammad K, Alloosh M, Vittal R, Sturek M
Submitted By Submitted Externally on 10/12/2020
Status Published
Journal Comparative medicine
Year 2020
Date Published 9/1/2020
Volume : Pages Not Specified : Not Specified
PubMed Reference 32972487
Abstract Metabolic Syndrome (MetS) has detrimental effects on the bladder, including
detrusor underactivity. The progression and mechanism of disease are poorly
understood. A swine model for diabetic bladder dysfunction (DBD) was established
because of the pig's human-sized bladder and its ability to develop MetS by
dietary modification alone. The hypothesis of this study is that this swine
model will demonstrate oxidative stress associated with MetS, which contributes
to both bladder fibrosis and detrusor underactivity (DU). Ossabaw pigs underwent
dietary modification consisting of a hypercaloric, atherogenic diet for 10 mo to
induce MetS, and were compared with a group of control (lean) pigs. Urodynamic
studies were performed in both groups to confirm DU. Thiobarbituric acid
reactive substances (TBARS) detected in the urine were used to measure oxidative
stress activity in the urinary tract, and urinary IL17a was used to detect
profibrotic activity. MetS was confirmed by assessing body weight, blood
pressure, glucose tolerance, total cholesterol, and triglycerides. The MetS
group exhibited an increase in the relative levels of urinary TBARS and IL17a.
Bladder pressures at capacity were lower in the MetS group, suggesting DU.
Histologic analysis of a cohort of control (lean) and MetS pigs revealed that as
compared with the control pigs, the MetS pigs had significantly more collagen in
the muscularis layer, but not in the submucosa or mucosa layer. In conclusion,
the Ossabaw pig model for diet-induced MetS is associated with oxidative stress
and profibrotic activity in the bladder, which results in DU. This has
previously been shown in mice and rats, but never in pigs. This novel model will
better represent human MetS and DBD because the mechanism and size of the pig
bladder more closely resemble that of a human, resulting in a more valid model
and facilitating further study into the signaling mechanisms responsible for
this impairment.