Background: Cellular inflammatory processes, fibrogenesis, and apoptosis are the
most characteristic pathologic features of colonic injury and colitis in human and
experimental animals. Obestatin, a peptide derived from proghrelin, is reported
to have significant protective and curative actions on many gastrointestinal tract
inflammatory diseases, including ulcerative colitis. However, its exact protective
mechanisms and the associated histopathological changes, are still in need of
deeper exploration. This study explores the effect of obestatin on the course of
acetic acid (AA)-induced colitis as an antifibrotic, anti-inflammatory, and anti-apoptotic
agent in relation to associated tissue stress parameters.
Materials and methods: A total of 40 healthy male albino Wistar rats weighing
200–250 g were recruited in this study. The rats were classified into four groups (10
rats each); group I: control, group II: obestatin only treated (16 nmol/kg), group III:
colitis induced group (AA 1 mL of 3.5% (v/v), and group IV: AA-induced colitis
+ obestatin for 14 days. Colonic samples were examined after staining haematoxylin
and eosin, Alcian blue, Masson trichrome. The expression of proliferating
cell nuclear antigen (PCNA), nuclear factor kappa B (NFkB), and caspase-3 was
estimated after immunohistochemical staining. Oxidative stress parameters, antioxidant
enzymes, tissue myeloperoxidase (MPO) activity, ghrelin, and fibrogenesis
markers were identified by immunoassay and colorimetric techniques.
Results: Colonic mucosa of group IV exhibited mucosal healing and regeneration
of the surface epithelium with the restoration of the goblet cells’ function together
with a decline in PCNA, NFkB, and caspase-3 immunoreactivity in comparison
to group III. This was accompanied by a reduction of the expression of fibrosis
markers, hydroxyproline and fibronectin. In addition, tissue antioxidant status was
significantly improved with a marked reduction of tissue MPO. Ghrelin level was
significantly increased in comparison to group III. Group IV exhibited significant
reduction in the levels of oxidative stress markers, malondialdehyde, total oxidant
status with a marked increase in the activity of antioxidant enzymes, superoxide
dismutase, catalase, and total cellular total antioxidant capacity.

Conclusions: The concomitant treatment of obestatin inhibits the development
of AA-induced colitis. The data signify that it has both curative and protective
effects via antifibrotic, antioxidant, and anti-inflammatory activities.