Upper gastrointestinal disorders induced by non-steroidal anti-inflammatory drugs

Chiba, Tetsuhiro; Sato, Kunihiko; Kudara, Norihiko; Shinozaki, H.; Ikeda, Kenichirou; Endo, Mayumi; Orii, Seishi; Suzuki, Kazuyuki

doi:10.1007/s10787-007-1578-0

Cited by 13 publications

(14 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NSAIDs block prostaglandin synthesis by inhibiting cyclooxygenases, leading to an erosion and then ulceration of the mucosal layer. These ulcers are most often seen in the gastric and duodenal region ( 30 ), although some studies have shown long-term NSAID users to have ileocecal ulceration as well ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration

Stroud

Nara

Roqueta‐Rivera

et al. 2009

Journal of Lipid Research

158

135

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org identifi ed as essential fatty acids that must be consumed in the diet. Once consumed, however, LA and ALA can both be desaturated and elongated into more highly unsaturated fatty acids (HUFA) such as arachidonic (AA), docosapentaenoic (DPA n-6), and docosahexaenoic (DHA) acids via the pathway shown in Fig. 1A . Delta-6 desaturase (D6D) performs the fi rst and rate-limiting step in this process, as well as the last step of desaturation for DHA and DPA n-6 synthesis. The D6D gene FADS2 was cloned in 1999 ( 2 ), and subsequently, a human case of D6D deficiency was identifi ed ( 3 ). The patient exhibited growth retardation accompanied by skin abnormalities, corneal ulceration, and feeding intolerance. Treatment with dietary AA and DHA restored normal growth and eliminated most other symptoms, underscoring the importance of the endogenous synthesis of these HUFAs.AA is a precursor to a host of signaling molecules known as eicosanoids, which include thromboxanes, leukotrienes, prostacyclins, and prostaglandins produced from the oxygenation of AA by cyclooxygenase and lipoxygenase enzymes. However, the symptoms of classic essential fatty acid defi ciency, growth retardation and dermatitis ( 1 ), are attributed to a loss of LA, not AA or eicosanoids. Because LA is an essential component of skin ceramides, LA defi ciency results in the disruption of the skin's water barrier function ( 4 ) and heat loss from skin ( 5 ). These side effects make investigation of AA defi ciency impossible by dietary manipulation without complications from LA defi ciency.DHA is found in large amounts in the retina, brain, and testes ( 6, 7 ). The role of DHA has been largely thought to be structural, increasing the fl uidity of cellular memAbstract Delta-6 desaturase (D6D) catalyzes the fi rst step in the synthesis of highly unsaturated fatty acids (HUFA) such as arachidonic (AA), docosapentaenoic (DPAn-6), and docosahexaenoic (DHA) acids, as well as the last desaturation of DPAn-6 and DHA. We created D6D-null mice ( ؊ / ؊ ), which enabled us to study HUFA defi ciency without depleting their precursors. In ؊ / ؊ , no in vivo AA synthesis was detected after administration of [U-

show abstract

Section: Discussionmentioning

confidence: 99%

“…HUFAs containing [26][27][28][29][30][31][32] carbons that are components of the sphingolipids present in spermatozoa ( 14 ). The exact function of these very long chain HUFAs in spermatogenesis is yet to be elucidated.…”

mentioning

confidence: 99%

Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration

Stroud

Nara

Roqueta‐Rivera

et al. 2009

Journal of Lipid Research

158

135

View full text Add to dashboard Cite

show abstract

“…The gastrointestinal and renal side effects are important untoward clinical events associated with the use of both selective and non-selective COX inhibitors (Gambaro and Perazella 2003;Sandhu and Heyneman 2004;Chiba et al 2008). Recently, it has been observed that co-administration of NSAIDs such as ibuprofen, meloxicam and celecoxib with paracetamol, most commonly used combination therapy clinically, produced synergistic nephrotoxicity and gastrotoxicity in rats (Kumar et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Although, non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of pharmacological therapy in the management of RA, their use is often associated with gastrointestinal ulcers and bleeding, in about 15-30% of the chronic users (James and Hawkey 2003;Kean and Buchanan 2005;Chiba et al 2008). Ibuprofen, a prototype of propionic acid derivative of NSAIDs group, is an effective and widely used drug to treat moderate to severe inflammatory conditions at the daily dose of 800-1,200 mg, including RA and osteoarthritis, since, it is preferentially accumulated and is retained in inflamed arthritic joints, where analgesic and antiinflammatory effects are required (Kilo et al 1995;Kean et al 1999;Rainsford 2009).…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen and hemin in adjuvant-induced arthritis in the Wistar rat

2011

View full text Add to dashboard Cite

show abstract

“…100 While NSAIDs are usually well tolerated for short periods of time, chronic use can lead to gastrointestinal complications (eg, ulcer formation, perforations, and bleeding), and renal toxicity. 101,102 Gene-based dosing for NSAIDs aimed at reducing the occurrence of ADRs is hindered by differing metabolic rates among various NSAIDs and the involvement of additional metabolizing enzymes (eg, CYP2C8). Individuals carrying the gene variants CYP2C8*3 (rs11572080; rs10509681), CYP2C9*2 (rs1799853) or CYP2C9*3 (rs1057910) show increased risk of developing acute gastrointestinal bleeding with NSAID therapy.…”

Section: Nsaidsmentioning

confidence: 99%

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

O’Rielly

Rahman

2010

PGPM

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology resulting in inflammation in the synovium, cartilage, and bone. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Outside the major histocompatibility complex (MHC) region, six additional risk loci have been identified and validated including PTPN22, STAT4, PADI4, CTLA4, TNFAIP3-OLIG3, and TRAF1/C5. Genetic factors are also important in RA pharmacotherapy due to the gene-dependent activity of enzymes involved in the pharmacokinetics and/or pharmacodynamics of RA medications. Indeed, there is great variability in drug efficacy as well as adverse events associated with any anti-rheumatic therapy and genetics is thought to contribute significantly to this inter-individual variability in response. This review will summarize the genetic factors that have been implicated in the pathogenesis of RA, and how these determinants may factor into the potential pharmacogenetics of this disease. We will also review the therapeutic agents that are currently being utilized or presently being evaluated in the treatment of RA, along with potential pharmacogenetic markers that have been proposed for such medications.

show abstract

Upper gastrointestinal disorders induced by non-steroidal anti-inflammatory drugs

Abstract: Patients 65 years old and over with continuous NSAIDs use had asymptomatic ulcers, and patients 80 years old and over had hemorrhagic ulcers.

Cited by 13 publications

References 8 publications

Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration

Disruption of FADS2 gene in mice impairs male reproduction and causes dermal and intestinal ulceration

Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen and hemin in adjuvant-induced arthritis in the Wistar rat

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

Contact Info

Product

Resources

About