Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors

Sud’ina, Galina F.; Pushkareva, Marina A.; Shephard, Pierre; Klein, Thomas

doi:10.1016/j.plefa.2007.12.006

Cited by 29 publications

(17 citation statements)

References 47 publications

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“…Because COX‐2 may be induced by cAMP‐elevating agents (Klein et al ., 2007), we next assessed whether the roflumilast‐mediated effects may be triggered via the COX pathway. For therapeutic modulation of COX, we used the NSAID diclofenac, an almost equipotent inhibitor of the two isoenyzmes of COX, COX‐1 and COX‐2, as measured biochemically and in human whole blood assays (Esser et al ., 2005; Sud'ina et al ., 2008). Considering the rapid and short half‐life of COX‐inhibitors, the non‐ulcerogenic dose of 1 mg·kg −1 of diclofenac was given orally 5 h before and 4 h after each administration of roflumilast on day 1 to 4 respectively.…”

Section: Resultsmentioning

confidence: 99%

“…In order to distinguish the role of COX‐1 versus COX‐2 in mediating the effects induced by roflumilast, a 5‐day short‐term tolerability experiment was performed using roflumilast with and without coadministration of 2 mg·kg −1 SC‐560 or lumiracoxib, given orally 5 h before and 4 h after administration of roflumilast respectively. SC‐560 is a COX inhibitor of the diaryl heterocycle class that is highly selective for COX‐1 (Smith et al ., 1998; Sud'ina et al ., 2008), whereas lumiracoxib is chemically related to diclofenac, but is highly selective for COX‐2 (Esser et al ., 2005; Sud'ina et al ., 2008). Coadministration of lumiracoxib but not of SC‐560 substantially prevented roflumilast‐mediated body weight loss, spleen weight loss, leukocytosis, blood neutrophilia and induction of serum CINC‐1 (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of cyclooxygenase‐2 prevents adverse effects induced by phosphodiesterase type 4 inhibitors in rats

Peter

Göggel

Colbatzky

et al. 2010

British J Pharmacology

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BACKGROUND AND PURPOSEPhosphodiesterase type 4 (PDE4) inhibitors such as roflumilast are currently being developed as anti-inflammatory treatments for chronic airway disorders. However, high doses of PDE4 inhibitors have also been linked to several side effects in different animal species, including pro-inflammatory effects in the rat. Here, we analysed PDE4-related toxicological findings in a rat model and how these side effects might be therapeutically prevented. EXPERIMENTAL APPROACHWistar rats were treated orally once daily with 10 mg·kg -1 roflumilast for 4 days. Macroscopic changes were monitored throughout the study and further parameters were analysed at the end of the experiment on day 5. In addition, the effects of concomitant treatment with cyclooxygenase (COX) inhibitors were assessed. KEY RESULTSSupratherapeutical treatment with roflumilast induced marked body and spleen weight loss, diarrhea, increased secretory activity of the harderian glands, leukocytosis, increased serum cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels, and histopathological changes in thymus, spleen, mesentery and mesenteric lymph nodes. All these toxicological findings could be prevented by the non-steroidal anti-inflammatory drug (NSAID) and non-selective COX inhibitor, diclofenac, given orally. Similar protective effects could be achieved by the COX-2 selective inhibitor lumiracoxib, whereas the COX-1 selective inhibitor SC-560 was generally not effective. CONCLUSIONS AND IMPLICATIONSTreatment with an NSAID inhibiting COX-2 prevents the major effects found after subchronic overdosing with the PDE4-specific inhibitor roflumilast. If this effect translates into humans, such combined treatment may increase the therapeutic window of PDE4 inhibitors, currently under clinical development. Abbreviations

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Inhibition of cyclooxygenase‐2 prevents adverse effects induced by phosphodiesterase type 4 inhibitors in rats

Peter

Göggel

Colbatzky

et al. 2010

British J Pharmacology

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“…The inhibitory effect on COX-2 reaction was assayed as described elsewhere (Sud'ina et al, 2008). Malondialdehyde generated from COX-2 reaction products is proportional to the COX-2 activity (Sharma et al, 2001), and could be detected at 532 nm as a 2-thiobarbituric acid reactive substance (Halliwell et al, 1987).…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

Free radical scavenging activities and inhibition of inflammatory enzymes of phenolics isolated from Tripodanthus acutifolius

Soberón¹,

Sgariglia²,

Sampietro³

et al. 2010

Journal of Ethnopharmacology

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“…Many chronic diseases including cardiovascular disease, diabetes, cancer, obesity, autoimmune diseases, rheumatoid arthritis, asthma and depression are associated with increased production of inflammatory mediators including thromboxane A2 (TXA2), leukotriene B4 (LTB4), IL-1, IL-6, tumor necrosis factor (TNF), and c-reactive protein [4,11,12]. Studies have shown that cancer development is associated with over expression of cyclooxygenase (COX) and lipoxygenase (LOX) [13].…”

Section: Anti-inflammatory and Effects Of N-3 Pufas In Colon Cancermentioning

confidence: 99%

The Pharmacological Effect of Omega-3 Fatty Acids Prevent Cancer Progression in Colon and Breast Cancer

Cm¹

2017

Austin J Nutri Food Sci

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Breast cancer and colon cancer are the common cancers in the world. Dietary fatty acids, n-3 polyunsaturated fatty acids (PUFAs), are believed to play an important role in preventing cancers. Studies have shown that long-chain n-3 PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are able to inhibit and prevent cancers. The present review evaluates DHA and EPA the role in the prevention of breast cancer and colon cancer. Further, anticancer mechanisms of action of DHA and EPA are also examined.Method: This review gathers the information from electronic and scientific literature database such as Pubmed, and Science Direct and so on. In this review, we focus on the pharmacological effects of DHA and EPA in breast cancer and colon cancer. Conclusion:This review suggests that n-3 PUFAs have anticancer effects and beneficial to human health.

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Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors

Cited by 29 publications

References 47 publications

Inhibition of cyclooxygenase‐2 prevents adverse effects induced by phosphodiesterase type 4 inhibitors in rats

Inhibition of cyclooxygenase‐2 prevents adverse effects induced by phosphodiesterase type 4 inhibitors in rats

Free radical scavenging activities and inhibition of inflammatory enzymes of phenolics isolated from Tripodanthus acutifolius

The Pharmacological Effect of Omega-3 Fatty Acids Prevent Cancer Progression in Colon and Breast Cancer

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