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Int J Mol Sci. 2018 Jun 1;19(6). pii: E1643. doi: 10.3390/ijms19061643.

Treatment with Obestatin-A Ghrelin Gene-Encoded Peptide-Reduces the Severity of Experimental Colitis Evoked by Trinitrobenzene Sulfonic Acid.

Author information

1
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland. kasia.konarska@uj.edu.pl.
2
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland. jakub.cieszkowski@uj.edu.pl.
3
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland. mpwarzec@cyf-kr.edu.pl.
4
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland. piotr.ceranowicz@uj.edu.pl.
5
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland. anna.1.chmura@uj.edu.pl.
6
Department of Clinical Biochemistry, Faculty of Medicine, Jagiellonian University Medical College, 31-501 Cracow, Poland. beata.kusnierz-cabala@uj.edu.pl.
7
Department of Pathomorphology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland. krystyna.galazka@uj.edu.pl.
8
Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jablonna, Poland. p.kowalczyk@ifzz.pl.
9
Department of Periodontology and Oral Diseases, Medical University of Warsaw, 00-246 Warsaw, Poland. andrzej.miskiewicz@wum.edu.pl.
10
Department of Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA. konturek@me.com.
11
Second Department of General Surgery, Faculty of Medicine, Jagiellonian University Medical College, 31-501 Cracow, Poland. michal.pedziwiatr@uj.edu.pl.
12
Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 31-531 Cracow, Poland. artur.dembinski@uj.edu.pl.

Abstract

Obestatin is a 23-amino acid peptide derived from proghrelin, a common prohormone for ghrelin and obestatin. Previous studies showed that obestatin exhibited some protective and therapeutic effects in the gut. The aim of our presented study was to examine the effect of treatment with obestatin on trinitrobenzene sulfonic acid (TNBS)-induced colitis. In rats anesthetized with ketamine, colitis was induced through intrarectal administration of 25 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Obestatin was administered intraperitoneally at doses of 4, 8, or 16 nmol/kg, twice per day for four consecutive days. The first dose of obestatin was given one day before the induction of colitis, and the last one was given two days after administration of TNBS. Fourteen days after the induction of colitis, rats were anesthetized again with ketamine, and the severity of colitis was determined. The administration of obestatin had no effect on the parameters tested in rats without the induction of colitis. In rats with colitis, administration of obestatin at doses of 8 or 16 nmol/kg reduced the area of colonic damage, and improved mucosal blood flow in the colon. These effects were accompanied by a reduction in the colitis-evoked increase in the level of blood leukocytes, and mucosal concentration of pro-inflammatory interleukin-1β. Moreover, obestatin administered at doses of 8 or 16 nmol/kg reduced histological signs of colonic damage. The administration of obestatin at a dose of 4 nmol/kg failed to significantly affect the parameters tested. Overall, treatment with obestatin reduced the severity of TNBS-induced colitis in rats. This effect was associated with an improvement in mucosal blood flow in the colon, and a decrease in local and systemic inflammatory processes.

KEYWORDS:

DNA synthesis; TNBS; colitis; colonic blood flow; ghrelin; interleukin-1β; myeloperoxidase; obestatin

PMID:
29865176
PMCID:
PMC6032262
DOI:
10.3390/ijms19061643
[Indexed for MEDLINE]
Free PMC Article

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