INT50058

Context Info Confidence 0.58 First Reported 1994 Last Reported 2010 Negated 5 Speculated 18 Reported most in Abstract Documents 907 Total Number 928 Disease Relevance 426.28 Pain Relevance 428.29

mitochondrion (Cpox) oxidoreductase activity (Cpox) cytoplasm (Cpox)

Anatomy Link Frequency platelet 17 spinal 17 stomach 11 brain 9 colon 9 Cpox (Rattus norvegicus)

Pain Link Frequency Relevance Heat cINOD 3844 100.00 Inflammation 1941 100.00 aspirin 1134 100.00 COX-2 inhibitor 1016 100.00 Pain 684 100.00 COX2 488 100.00 cytokine 354 100.00 Paracetamol 317 100.00 cOX1 316 100.00 Inflammatory response 86 100.00

Disease Link Frequency Relevance Heat INFLAMMATION 2990 100.00 Cancer 475 100.00 Injury 413 100.00 Colon Cancer 207 100.00 Colorectal Cancer 49 100.00 Experimental Autoimmune Neuritis 26 100.00 Depression 7 100.00 Pain 665 99.92 Hypersensitivity 416 99.92 Ulcers 190 99.92

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In spite of the inhibition of COX activity displayed in vitro, the compounds did not cause gastric damage in rats after acute oral administration.

Negative_regulation (inhibition) of COX

1) Confidence 0.58 Published 2007 Journal Medicinal chemistry (Sh?riqah (United Arab Emirates)) Section Abstract Doc Link 17348851 Disease Relevance 0 Pain Relevance 0.34

HCys dose dependently impaired cytochrome c oxidase (COX) activity as well as stability and induced reactive oxygen species and apoptotic cell death.

Negative_regulation (impaired) of COX in apoptotic cell associated with apoptosis and death

2) Confidence 0.57 Published 2006 Journal Neurobiol. Dis. Section Abstract Doc Link 16876425 Disease Relevance 0.97 Pain Relevance 0.09

However, since both cyclooxygenase (COX) inhibitors have a short half-life, the current report presents drug developmental effects after triple daily doses administration, as they are used in human.

Negative_regulation (inhibitors) of COX

3) Confidence 0.56 Published 2004 Journal Birth Defects Res. B Dev. Reprod. Toxicol. Section Abstract Doc Link 15505808 Disease Relevance 0.17 Pain Relevance 0.09

Whereas paracetamol inhibited only COX enzyme activity, caffeine also inhibited COX-2 protein synthesis.

Negative_regulation (inhibited) of COX enzyme associated with paracetamol

4) Confidence 0.55 Published 2000 Journal Neuropharmacology Section Abstract Doc Link 10963764 Disease Relevance 0 Pain Relevance 1.07

These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner.

Negative_regulation (inhibited) of COX associated with inflammation and analgesic

5) Confidence 0.54 Published 2006 Journal Arch. Pharm. Res. Section Abstract Doc Link 17121179 Disease Relevance 0.83 Pain Relevance 0.92

These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity.

Negative_regulation (inhibition) of COX associated with inflammation

6) Confidence 0.54 Published 2006 Journal Arch. Pharm. Res. Section Abstract Doc Link 17121179 Disease Relevance 0.68 Pain Relevance 0.75

The production of prostaglandin E2 (PGE2), a major metabolite of COX, is increased in numerous human cancers including esophageal SCC, therefore, inhibition of COX activity and subsequent suppression of the formation of PGE2 may be chemopreventive in the esophagus.

Negative_regulation (inhibition) of COX in esophagus associated with cancer and skin cancer

7) Confidence 0.53 Published 2005 Journal Carcinogenesis Section Abstract Doc Link 15878914 Disease Relevance 0.79 Pain Relevance 0.22

This decrease is thought to correlate with the inhibition of cyclooxygenase (COX) activity.

Negative_regulation (inhibition) of COX

8) Confidence 0.53 Published 2005 Journal Carcinogenesis Section Abstract Doc Link 15878914 Disease Relevance 0.59 Pain Relevance 0.22

The purpose of this study was to determine whether concurrent inhibition of COX and carbonic anhydrase would produce a teratogenic profile that includes both VSD and DH.

Spec (whether) Negative_regulation (inhibition) of COX associated with hiatal hernia and ventricular heart septal defects

9) Confidence 0.52 Published 2005 Journal Drug Chem Toxicol Section Abstract Doc Link 16298872 Disease Relevance 0.93 Pain Relevance 0.40

Therefore, while concurrent inhibition of COX and carbonic anhydrase did not produce DH, potentiation was noted for the induction of VSD and appendicular anomalies.

Negative_regulation (inhibition) of COX associated with hiatal hernia and ventricular heart septal defects

10) Confidence 0.52 Published 2005 Journal Drug Chem Toxicol Section Abstract Doc Link 16298872 Disease Relevance 0.93 Pain Relevance 0.19

To inhibit both COX and carbonic anhydrase, ibuprofen (COX inhibitor) and acetazolamide (carbonic anhydrase inhibitor) were coadministered on GDs 9-10.

Negative_regulation (inhibit) of COX

11) Confidence 0.52 Published 2005 Journal Drug Chem Toxicol Section Abstract Doc Link 16298872 Disease Relevance 0.97 Pain Relevance 0.38

The use of this NSAID in Alzheimer's disease (AD) is hampered by a significant gastrointestinal toxicity associated with cyclooxygenase (COX) inhibition.

Negative_regulation (inhibition) of COX associated with toxicity, cinod and disease

12) Confidence 0.46 Published 2005 Journal J. Med. Chem. Section Abstract Doc Link 16134939 Disease Relevance 0.64 Pain Relevance 0.29

OBJECTIVE: There is a lack of correlation between cyclooxygenase (COX) inhibition and nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) damage; it has been suggested that mucosal damage may be initiated by a "topical" action of NSAIDs involving mitochondrial injury.

Negative_regulation (inhibition) of COX associated with inflammation, injury and cinod

13) Confidence 0.44 Published 1996 Journal Arthritis Rheum. Section Abstract Doc Link 8961904 Disease Relevance 0.27 Pain Relevance 0.37

Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel.

Negative_regulation (inhibitor) of COX in bowel

14) Confidence 0.43 Published 2004 Journal Braz. J. Med. Biol. Res. Section Abstract Doc Link 15060699 Disease Relevance 0.26 Pain Relevance 0.31

Studies suggest that cyclooxygenase (COX) contributes to ischemic neuronal damage and that COX inhibitors may reduce injury.

Negative_regulation (inhibitors) of COX in neuronal associated with injury

15) Confidence 0.42 Published 2005 Journal Anesth. Analg. Section Abstract Doc Link 15781534 Disease Relevance 0.74 Pain Relevance 0.68

BACKGROUND: Patients with aspirin-sensitive respiratory and skin diseases experience cross reactions to all nonsteroidal anti-inflammatory drugs (NSAIDs) which inhibit cyclooxigenase (COX) enzymes.

Negative_regulation (inhibit) of COX in respiratory associated with aspirin, inflammation, skin diseases and cinod

16) Confidence 0.42 Published 2006 Journal J Investig Allergol Clin Immunol Section Abstract Doc Link 17153884 Disease Relevance 0.35 Pain Relevance 0.36

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, celecoxib, and etoricoxib are reported to act as chemopreventive agents in experimental colon cancer induced by 1,2-dimethylhydrazine (DMH) as they are known cyclooxygenase (COX) enzyme inhibitors.

Negative_regulation (inhibitors) of COX in colon associated with aspirin, inflammation, colon cancer and cinod

17) Confidence 0.42 Published 2007 Journal Drug Chem Toxicol Section Abstract Doc Link 17934920 Disease Relevance 0.56 Pain Relevance 0.53

Sodium valproate, a mood stabilizer, when chronically administered to rats (200 mg/kg i.p. daily for 30 days) significantly reduced the brain protein levels of cyclooxygenase (COX)-1 and COX-2, without altering the mRNA levels of these enzymes.

Negative_regulation (reduced) of COX in brain

18) Confidence 0.41 Published 2003 Journal J. Neurochem. Section Abstract Doc Link 12694395 Disease Relevance 0 Pain Relevance 0

On the strength of in vitro, in vivo, observational, and clinical data, nonsteroidal antiinflammatory drugs (NSAIDs)-also referred to as COX inhibitors-have emerged as lead compounds for cancer prevention, and possible adjuncts to cancer therapy.

Negative_regulation (inhibitors-have) of COX associated with inflammation, cancer and cinod

19) Confidence 0.41 Published 2003 Journal Am. J. Clin. Oncol. Section Abstract Doc Link 12902856 Disease Relevance 0.46 Pain Relevance 0.19

In all organs investigated both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dependent manner, but ketorolac tromethamine was more potent and had a longer-lasting effect than lysine clonixinate.

Negative_regulation (inhibited) of COX associated with acular

20) Confidence 0.41 Published 1995 Journal Life Sci. Section Abstract Doc Link 7603299 Disease Relevance 0.12 Pain Relevance 0.59

General Comments

This test has worked.