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

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


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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Antioxidants / therapeutic use*
  • Capsule Endoscopy
  • Carnitine / therapeutic use
  • Disease Models, Animal
  • Female
  • Humans
  • Intestine, Small*
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Oxidative Stress*
  • Peptic Ulcer / blood
  • Peptic Ulcer / chemically induced*
  • Peptic Ulcer / drug therapy*
  • Peptic Ulcer / pathology
  • Reactive Oxygen Species / blood


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Reactive Oxygen Species
  • Carnitine