Enhanced anti‐inflammatory potency of a nitric oxide‐releasing prednisolone derivative in the rat

  title={Enhanced anti‐inflammatory potency of a nitric oxide‐releasing prednisolone derivative in the rat},
  author={Fusun Turesin and Piero del Soldato and John L Wallace},
  journal={British Journal of Pharmacology},
Derivatization of nonsteroidal anti‐inflammatory drugs, such that they release nitric oxide (NO) in small amounts, has been shown to significantly increase their anti‐inflammatory activity and analgesic potency. In this study, we compared the anti‐inflammatory potency of prednisolone to a nitric oxide‐releasing derivative of prednisolone (NCX‐1015). Carrageenan‐induced inflammation of an airpouch in the rat was used. The rats were pretreated with equimolar doses of prednisolone or NCX‐1015 and… 

Enhanced Anti-Inflammatory Potency of a Nitric Oxide-Releasing Derivative of Flunisolide: Role of Nuclear Factor-κB

NCX-1024 may be an attractive alternative to conventional glucocorticoids, particularly for applications involving topical administration, and is found to be 41 times more potent than flunisolide in reducing leukocyte accumulation and prostaglandin E2 generation.

Anti‐inflammatory effects of nitric oxide‐releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis

It is shown that NO‐hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.

The nitrosterols – a step forward from the steroid anti-inflammatory drugs?

  • S. Doggrell
  • Biology, Medicine
    Expert opinion on investigational drugs
  • 2005
Initial studies show that NO-releasing forms of prednisolone, flunisolide and hydrocortisone (the nitrosterols) are more potent anti-inflammatory agents than their parent molecules in animal models of acute and chronic inflammation, however, given that prolonged exposure to high concentrations of NO may be pro-inflammatory, further long-term studies are needed to determine whether the increased anti- inflammatory effects observed with short-term treatment with nitrosters are maintained.

Building a better aspirin: gaseous solutions to a century‐old problem

  • J. Wallace
  • Medicine
    British journal of pharmacology
  • 2007
The NO‐NSAIDs and H2S‐releasing NSAIDs represent examples of new anti‐inflammatory drugs with greatly reduced toxicity and improved therapeutic activity, both created through the concept of exploiting the beneficial effects of endogenous gaseous mediators.

Aspirin, but not NO-releasing aspirin (NCX-4016), interacts with selective COX-2 inhibitors to aggravate gastric damage and inflammation

The notion that NCX-4016 may be an attractive alternative to aspirin for indications such as cardioprotection, including in individuals also taking selective COX-2 inhibitors, is supported.

Mechanisms of the anti‐inflammatory effects of the natural secosteroids physalins in a model of intestinal ischaemia and reperfusion injury

The in vivo anti‐inflammatory actions of physalins, natural steroidal compounds, appear to be mostly due to the activation of glucocorticoid receptors.


AP severity was significantly ameliorated by NO-NSAIDs being the administration time essential to achieve optimal pancreatic protection that may result to be useful in the prevention of postendoscopic severe AP.

Suppressive effects of nitric oxide‐releasing prednisolone NCX‐1015 on the allergic pleural eosinophil recruitment in rats

Background The addition of a nitric oxide (NO)‐releasing moiety to prednisolone was shown to enhance the anti‐inflammatory activity of this glucocorticoid in some experimental conditions, but its

The Distinct Alterations Produced in Cardiovascular Functions by Prednisolone and Nitro-prednisolone (NCX-1015) in the Rat Highlight a Causal Role for Endothelin-1

A lack of occurrence of cardiovascular alterations by nitro-releasing derivative of prednisolone (NCX-1015) is indicated, and a functional link between predisonsolone effects and the endogenous endothelin-1 system is found.



21‐NO‐prednisolone is a novel nitric oxide‐releasing derivative of prednisolone with enhanced anti‐inflammatory properties

NCX‐1015 is shown to be more potent than prednisolone in controlling several, though not all, parameters of acute and chronic inflammation, and it is proposed that this effect may be due to a co‐operation between the steroid moiety and nitric oxide or related species released in biological fluids.

Inhibition of inducible nitric oxide synthase expression by novel nonsteroidal anti‐inflammatory derivatives with gastrointestinalsparing properties

The results indicate that NO‐NSAIDs can inhibit the inducible L‐arginine‐NO pathway, and are capable of suppressing NO synthesis by inhibiting expression of NO synthase.

Potent antiarthritic properties of a glucocorticoid derivative, NCX-1015, in an experimental model of arthritis

The improved antiarthritic properties of a nitric oxide-releasing derivative of prednisolone that includes a sparing of the effects on bone are described, which has milder side effects anticipated on the bone compartment.

NCX-1015, a nitric-oxide derivative of prednisolone, enhances regulatory T cells in the lamina propria and protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice

In vivo treatment with NCX-1015 potently stimulated IL-10 production, suggesting that the NO steroid induces a regulatory subset of T cells that negatively modulates intestinal inflammation.

NCX-4016 (NO-Aspirin) Inhibits Lipopolysaccharide-Induced Tissue Factor Expression In Vivo: Role of Nitric Oxide

NCX-4016 prevents monocyte TF expression; this is accompanied by inhibition of TX and cytokine biosynthesis, and these additive effects of nitric oxide release and COX inhibition may help explain efficacy and tolerability of NCX- 4016.

Nitroparacetamol exhibits anti‐inflammatory and anti‐nociceptive activity

Compared with paracetamol, nitropar acetamol not only exhibits augmented antinociceptive activity in both rat and mouse but, intriguingly, is also anti‐inflammatory over a similar dose range.

Anti-thrombotic effects of a nitric oxide-releasing, gastric-sparing aspirin derivative.

It is demonstrated that NCX 4215 has comparable or enhanced anti-thrombotic activity to that of aspirin, but does not cause gastric damage or alter systemic blood pressure.

IL-1β Converting Enzyme Is a Target for Nitric Oxide-Releasing Aspirin: New Insights in the Antiinflammatory Mechanism of Nitric Oxide-Releasing Nonsteroidal Antiinflammatory Drugs

It is shown that incubating human monocytes with NCX-4016 causes intracellular NO formation and suppresses IL-1β and IL-18 processing by inhibiting caspase-1 activity, a new, cycloxygenase-independent antiinflammatory mechanism of NO-aspirin.

An NO derivative of ursodeoxycholic acid protects against Fas-mediated liver injury by inhibiting caspase activity

Evidence that a nitric oxide (NO) derivative of ursodeoxycholic acid (UDCA), NCX-1000 protects against liver damage in murine models of autoimmune hepatitis by inhibiting both the proapoptotic and the proinflammatory branches of the caspase superfamily is provided.