Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID‐enteropathy in the rat

@article{Somasundaram2000UncouplingOI,
  title={Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID‐enteropathy in the rat},
  author={Somasundaram and Sigthorsson and Simpson and Watts and Jacob and Tavares and Rafi and Roseth and Foster and Terry L. Price and Wrigglesworth and Bjarnason},
  journal={Alimentary Pharmacology \& Therapeutics},
  year={2000},
  volume={14}
}
The pathogenesis of NSAID‐induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation. 
A study of the effects of indometacin on liver mitochondria from rats, mice and humans
TLDR
A part of the mechanism of the gastrointestinal toxicity exhibited by non‐steroidal anti‐inflammatory drugs is believed to involve the uncoupling of mitochondrial oxidative phosphorylation, and studies have used rat liver mitochondria for this purpose.
Uric acid ameliorates indomethacin‐induced enteropathy in mice through its antioxidant activity
TLDR
This study aimed to determine whether uric acid could reduce end points associated with nonsteroidal anti‐inflammatory drug (NSAID)‐induced enteropathy.
NSAID-induced intestinal damage: are luminal bacteria the therapeutic target?
suggests that inhibition of both COX-1 and COX-2 is necessary to cause significant GI damage. The importance of PG deficiency in the pathogenesis of NSAIDinduced intestinal damage is confirmed by the
NSAID-induced gastrointestinal damage: the biochemical consequences of the 'ion trapping' hypothesis
TLDR
It is suggested that the 'topical' effect of NSAIDs is instrumental in initiating the intestinal damage of conventional NSAIDs and that inhibition of COX modifies this response leading to severe inflammation and ulcers.
The role of mitochondria-derived reactive oxygen species in the pathogenesis of non-steroidal anti-inflammatory drug-induced small intestinal injury
TLDR
By clarifying the precise mechanism, together with its clinical features using novel endoscopy, effective strategies for preventing NSAID-induced small intestinal damage, especially targeting mitochondria-derived ROS production, may be developed.
Oral glutamine attenuates indomethacin-induced small intestinal damage.
TLDR
The use of NSAIDs (non-steroidal anti-inflammatory drugs), although of great therapeutic value clinically, is limited by their tendency to cause mucosal damage in the gastrointestinal tract, and glutamine is a fuel preferentially used by enterocytes and is known to contribute to maintaining the integrity of these cells.
Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin
TLDR
In addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.
Determinants of the short‐term gastric damage caused by NSAIDs in man
Background The short‐term gastric damage seen with non‐steroidal anti‐inflammatory drugs (NSAIDs) in man may involve inhibition of cyclooxygenase (COX‐1) and COX‐2 as well as the topical irritancy,
Indomethacin Increases the Efficacy of Oxygen Utilization of Colonic Mitochondria and Uncouples Hepatic Mitochondria in Tissue Homogenates From Healthy Rats
TLDR
Indomethacin affected parameters of mitochondrial function in an organ-specific and concentration-dependent manner and the large increase in ADP/O ratio in complex I at the highest concentration likely reflects terminal uncoupling.
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References

SHOWING 1-10 OF 91 REFERENCES
MECHANISMS UNDERLYING GASTRIC MUCOSAL DAMAGE INDUCED BY INDOMETHACIN AND BILE‐SALTS, AND THE ACTIONS OF PROSTAGLANDINS
  • B. Whittle
  • Medicine, Biology
    British journal of pharmacology
  • 1977
1 The mechanisms by which the bile salt, sodium taurocholate, potentiates the formation of gastric mucosal erosions induced by indomethacin has been investigated in the rat.
Non-steroidal anti-inflammatory drug gastropathy and cytoprotection: pathogenesis and mechanisms re-examined.
  • J. Wallace
  • Medicine
    Scandinavian journal of gastroenterology. Supplement
  • 1992
TLDR
The contribution of neutrophils to the mucosal damage induced by NSAIDs is discussed, as is the possibility that prostaglandins protect the gastrointestinal mucosa from NSAID-induced ulceration at least in part through inhibitory effects on neutrophil function.
Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation.
TLDR
The ability to uncouple mitochondrial oxidative phosphorylation is a common characteristic of antiinflammatory agents with an ionizable group and could lead to improved NSAID GI safety.
NSAID mechanism of action: the role of intracellular pharmacokinetics
TLDR
Nonsteroid anti-inflammatory drugs (NSAIDs) are a structurally diverse group of agents with similar therapeutic effects and are also associated with lowered risks of cardiovascular disease and colon cancer.
The respiratory chain and oxidative phosphorylation.
TLDR
How the respiratory chain and oxidative phosphorylation works and which substances may disable it are explained.
Pre‐ulcerative villous contraction and microvascular induced by indomethacin in the rat jejunum: a detailed morphological study
Background: In indomethacin‐induced jejunal ulceration in the rat, villi undergo both early microvascular injury and shortening that may involve activation of villous smooth muscle.
Mitochondrial damage: a possible mechanism of the “topical” phase of NSAID induced injury to the rat intestine
TLDR
In vivo studies with nabumetone and aspirin suggested that uncoupling or inhibition of electron transport underlies the “topical” phase of NSAID induced damage.
Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.
TLDR
Nitroxybutyl-flurbiprofen is associated with significantly less macroscopic damage in the small intestine than flurbip rofen but was associated with mitochondrial damage in vivo and caused similar increases in permeability of the small intestinal, suggesting that its beneficial effect is on the later pathogenic stages of the damage.
NO‐naproxen vs. naproxen: ulcerogenic, analgesic and anti‐inflammatory effects
TLDR
The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti‐inflammatory properties to the parentNSAID.
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