| Carbon monoxide reverses diabetic gastroparesis in NOD mice. | |
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MedLine Citation:
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PMID: 20378827 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Diabetic gastroparesis is associated with increased oxidative stress attributable to loss of upregulation of heme oxygenase-1 (HO1), with resultant damage to interstitial cells of Cajal and delayed gastric emptying. These changes can be reversed by induction of HO1. HO1 catalyzes the breakdown of heme into iron, biliverdin and, carbon monoxide (CO). The aim of this study was to determine whether inhalation of CO can mimic the protective effects of HO1. Nonobese diabetic (NOD) mice with delayed gastric emptying were treated with CO inhalation. Serum malondialdehyde was measured as a marker of oxidative stress. Gastric emptying of solids was measured using a [(13)C]octanoic acid breath test. Kit expression levels were determined in immunoblots of protein extracted from the external muscle layers of the gastric body and antrum. The effect of CO on oxidative stress and gastric emptying was also determined in the presence of HO activity inhibitor chromium mesoporphyrin. CO inhalation reduced oxidative stress, restored Kit expression and reversed delayed gastric emptying in diabetic NOD mice with delayed gastric emptying. CO inhalation maintained this effect in the presence of the HO activity inhibitor, chromium mesoporphyrin, also resulting in restoration of the delay in gastric emptying. CO inhalation mimics the protective effect of upregulation of HO1 and decreased oxidative stress, increased Kit expression, and restored delay in gastric emptying. This effect of CO was independent of HO activity, suggesting that its effects were downstream of HO1. CO represents a potential therapeutic option for treatment of diabetic gastroparesis. |
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Authors:
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Purna C Kashyap; Kyoung Moo Choi; Nirjhar Dutta; David R Linden; Joseph H Szurszewski; Simon J Gibbons; Gianrico Farrugia |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-04-08 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: 298 ISSN: 1522-1547 ISO Abbreviation: Am. J. Physiol. Gastrointest. Liver Physiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-17 Revised Date: 2012-02-22 |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: United States |
Other Details:
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Languages: eng Pagination: G1013-9 Citation Subset: IM |
Affiliation:
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Mayo Clinic, 200 First St. SW, Rochester MN 55905, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carbon Monoxide / pharmacology* Diabetes Complications / drug therapy* Female Gastric Emptying / drug effects Gastroparesis / drug therapy* Mice Mice, Inbred NOD Oxidative Stress |
| Grant Support | |
ID/Acronym/Agency:
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DK57061/DK/NIDDK NIH HHS; DK68055/DK/NIDDK NIH HHS; P01 DK068055-050001/DK/NIDDK NIH HHS; P30 DK084567-01/DK/NIDDK NIH HHS; P30DK084567/DK/NIDDK NIH HHS; R01 DK057061-11/DK/NIDDK NIH HHS; R01 DK057061-12/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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630-08-0/Carbon Monoxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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