Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells

Kawai, Shinichi; Nishida, Shinichi; Kato, Miyako; Furumaya, Yasuko; Okamoto, Ryo; Koshino, Tomihisa; Mizushima, Yutaka

doi:10.1016/s0014-2999(98)00078-8

Cited by 110 publications

(80 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is known that IL-1␤ induces COX-2 but not COX-1 expression in synovial cells (Kawai et al, 1998). However, treatment with IL-1␤ (1 ng/ml) did not influence the effects of NSAIDs on the proliferation of synovial cells (data not shown).…”

Section: Resultsmentioning

confidence: 79%

“…Rheumatoid synovial cells were prepared from synovial tissues as described previously with slight modification (Kawai et al, 1998;Yamazaki et al, 2000). The synovial tissues were obtained during a total knee replacement from patients with rheumatoid arthritis who fulfilled the revised American Rheumatism Association criteria for the classification of rheumatoid arthritis (Arnett et al, 1988).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Yamazaki¹,

Kusunoki²,

Matsuzaki³

et al. 2002

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce apoptosis in a variety of cell lines. In this study, we examined the effect of NSAIDs on the growth and apoptosis of synovial cells from patients with rheumatoid arthritis and analyzed the activation of peroxisome proliferator-activated receptor ␥ (PPAR␥) as a possible mechanism of action of NSAIDs. Cell proliferation and viability were assessed from 5-bromo-2Ј-deoxyuridine incorporation and by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay, respectively. The apoptosis of synovial cells was identified by DNA fragmentation assay and terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling assay. Indometacin, diclofenac, oxaprozin, and zaltoprofen reduced cell proliferation and induced apoptotic cell death in synovial cells, whereas ketoprofen and acetaminophen did not. N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, also inhibited cell proliferation, whereas it did not cause apoptosis. Rheumatoid synovial cells expressed PPAR␥ mRNA, and the PPAR␥ ligands 15-deoxy-⌬ 12,14 -prostaglandin J 2 and troglitazone reduced the proliferation and induced apoptosis in synovial cells. Luciferase reporter assay demonstrated that not only PPAR␥ ligands but also NSAIDs, which could induce apoptosis, increased the activation of PPAR␥ in synovial cells. Furthermore, the ability of NSAIDs and PPAR␥ ligands to stimulate the activation of PPAR␥ correlated with their ability to decrease cell viability(r ϭ 0.92, p Ͻ 0.01) and ability to induce DNA fragmentation (r ϭ 0.97, p Ͻ 0.001) in synovial cells. These results suggest that PPAR␥ is an attractive target for induction of apoptosis in rheumatoid synovial cells and that the activation of the PPAR␥ pathway is associated with the apoptotic action of NSAIDs.

show abstract

Section: Resultsmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Yamazaki¹,

Kusunoki²,

Matsuzaki³

et al. 2002

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…The C max following the fourth IV dose was 3090 g/ml and 5617 ng/ml, for 18.75 and 37.5 mg, respectively. AUC (0)(1)(2)(3)(4)(5)(6) following the fourth dose of 18.75 and 37.5 mg were 935 and 1839 ngÁhour/ml, respectively. The C max and AUC following the first and fourth doses were similar, suggesting no accumulation of IV HPbCD-diclofenac.…”

Section: Studymentioning

confidence: 94%

“…1,2 Recent studies have further demonstrated that diclofenac opens KCNQ2/3 potassium channels and inhibits sensory neuronal depolarization, resulting in analgesia. 3 Diclofenac has long been approved as safe and effective for both acute and chronic pain through a variety of routes.…”

mentioning

confidence: 99%

Single‐Dose and Multiple‐Dose Pharmacokinetics and Dose Proportionality of Intravenous and Intramuscular HPβCD‐Diclofenac (Dyloject) Compared with Other Diclofenac Formulations

Mermelstein¹,

Hamilton²,

Wright

et al. 2013

Pharmacotherapy

View full text Add to dashboard Cite

STUDY OBJECTIVE To evaluate single-and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-b-cyclodextrin (HPbCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. DESIGN Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. SETTING Clinical research center. SUBJECTS Healthy adult volunteers. INTERVENTION Study 1: Subjects received HPbCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPbCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. MEASUREMENTS AND MAIN RESULTS Study 1: IV HPbCD-diclofenac had a higher peak plasma concentration (C max ) and earlier time to reach maximum plasma concentration (T max ), but equivalent plasma exposure (area under the curve from time zero to t [AUC 0-t ]) to IV Voltarol. The geometric mean ratio of HPbCD-diclofenac (IV) to Voltarol (IV) for AUC 0-t was 106.27%. The geometric mean ratio of HPbCD-diclofenac (IM) to Voltarol (IM) for AUC 0-t was 110.91%. The geometric mean ratio of HPbCD-diclofenac (IV) to HPbCD-diclofenac (IM) for AUC 0-t was 101.25%. The geometric mean ratio of HPbCD-diclofenac (IM) to Voltarol (IV) for AUC 0-t was 104.96%. Study 2: C max for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPbCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ngÁhour/ml) and 37.5 mg (1843 ngÁhour/ml) IV HPbCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ngÁhour/ml). CONCLUSIONS Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPbCD-diclofenac compared with Voltarol and after IM administration of HPbCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPbCD-diclofenac was equivalent to IV administration of HPbCD-diclofenac and IV administration of Voltarol. Study 2: HPbCDdiclofenac showed dose proportionality after single-and multiple-dose administration and no accumulation of HPbCD-diclofenac. HPbCD-diclofenac was safe and well tolerated following IV and IM administration.

show abstract

“…With the exception of celecoxib, which is COX-2 specific, NSAIDs used in Figure 4 can inhibit both subtypes. 20 Therefore, if the induction of CHOP mRNA by indomethacin is caused by COX inhibition in gastric mucosal cells (in other words, inhibition of COX-1), higher concentrations of celecoxib would be required to reveal an effect. Given that the reverse was the case, it appears that CHOP induction by NSAIDs is not related to inhibition of COX and PG synthesis in gastric mucosal cells.…”

Section: Induction Of Grp78 and Chop By Indomethacin Associated With mentioning

confidence: 99%

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

et al. 2004

View full text Add to dashboard Cite

Apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs) is involved not only in the production of NSAIDinduced gastric lesions but also in the antitumor activity of these drugs. The endoplasmic reticulum (ER) stress response is a cellular mechanism that aids in protecting the ER against ER stressors and is involved in ER stressor-induced apoptosis. Here, we examine the relationship between this response and NSAID-induced apoptosis in cultured guineapig gastric mucosal cells. Exposure of cells to indomethacin, a commonly used NSAID, induced GRP78 as well as CHOP, a transcription factor involved in apoptosis. Three factors that positively regulate CHOP expression (ATF6, ATF4 and XBP-1) were activated and/or induced by indomethacin. NSAIDs other than indomethacin (diclofenac, ibuprofen and celecoxib) also induced CHOP. Monitoring of the transcriptional activities of ATF6 and CHOP by luciferase assay revealed that both were stimulated in the presence of indomethacin. Furthermore, indomethacin-induced apoptosis was suppressed in cultured guinea-pig gastric mucosal cells by expression of the dominant-negative form of CHOP, or in peritoneal macrophages from CHOP-deficient mice. These results suggest that ER stress response-related proteins, particularly CHOP, are involved in NSAID-induced apoptosis.

show abstract

Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells

Cited by 110 publications

References 28 publications

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor γ in Rheumatoid Synovial Cells

Single‐Dose and Multiple‐Dose Pharmacokinetics and Dose Proportionality of Intravenous and Intramuscular HPβCD‐Diclofenac (Dyloject) Compared with Other Diclofenac Formulations

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

Contact Info

Product

Resources

About