Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.
OBJECTIVE
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.
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yoshiyasu
Y
Kono
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Seiji
S
Kawano
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Akinobu
A
Takaki
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yasuyuki
Y
Shimomura
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Masahiro
M
Onji
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hisashi
H
Ishikawa
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Sakuma
S
Takahashi
Department of Gastroenterology, Fukuyama Medical Center, Fukuyama, Japan.
Joichiro
J
Horii
Department of Internal Medicine, Fukuyama City Hospital, Fukuyama, Japan.
Sayo
S
Kobayashi
Department of Internal Medicine, Tsuyama Chuo Hospital, Tsuyama, Japan.
Daisuke
D
Kawai
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Kazuhide
K
Yamamoto
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hiroyuki
H
Okada
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000975:Antioxidants / Q000627:therapeutic use*; D053704:Capsule Endoscopy; D002331:Carnitine / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007421:Intestine, Small; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018384:Oxidative Stress; D010437:Peptic Ulcer / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000097:blood
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D017382:Reactive Oxygen Species; D002331:Carnitine
L-carnitine; mitochondria; non-steroidal anti-inflammatory drugs (NSAIDs); oxidative stress; vitamin E