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J Gastroenterol Hepatol. 2017 Jan;32(1):136-145. doi: 10.1111/jgh.13424.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

Author information

1
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
2
Department of Gastroenterology, Fukuyama Medical Center, Fukuyama, Japan.
3
Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan.
4
Department of Internal Medicine, Tsuyama Chuo Hospital, Tsuyama, Japan.

Abstract

BACKGROUND AND AIM:

Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model.

METHODS:

A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group).

RESULTS:

Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N.

CONCLUSIONS:

Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

KEYWORDS:

L-carnitine; mitochondria; non-steroidal anti-inflammatory drugs (NSAIDs); oxidative stress; vitamin E

PMID:
27118323
DOI:
10.1111/jgh.13424
[Indexed for MEDLINE]

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