The role of non-steroidal anti-inflammatory drugs in acute liver injury.

The chemokine fractalkine (C–X3–C motif chemokine ligand 1, CX3CL1) and its receptor (C–X3–C motif chemokine receptor 1, CX3CR1) are known to mediate leukocyte chemotaxis, adhesion, and survival. In the liver, CX3CR1 is expressed on multiple cell types including monocytes and dendritic cells. However, the function of CX3CR1 on hepatic dendritic cells (HDCs) is still poorly understood. In the present study, we investigated the role of CX3CR1 on mouse HDCs during homeostasis and following acute liver injury. At homeostasis, CX3CR1 expression was detected amongst CD11b+/CD103− type 2 myeloid HDCs (mHDCs) and these cells were characterized by the production of interleukin-10 (IL-10). Mice treatment with the hepatotoxic agent carbon tetrachloride (CCl4) up-regulated liver IL-10 expression and stimulated the expansion of CX3CR1+ mHDCs which also showed a more mature phenotype. The absence of CX3CR1 in naïve CX3CR1gfp/gfp mice specifically reduced the CD11b+/IL-10+ mHDCs as compared with CX3CR1-proficient animals (CX3CR1+/gfp). Following CCl4 poisoning, the liver recruitment and maturation of CD11b+ mHDCs was significantly attenuated in CX3CR1gfp/gfp mice. Furthermore, these mice suffered more severe hepatic injury and inflammation than CX3CR1+/gfp mice and showed a delated recovery from liver damage. Such a worsening of liver injury in CX3CR1gfp/gfp mice was associated with an impaired up-regulation of hepatic IL-10 expression and a lower number of IL-10 producing CD11b+ mHDCs. Consistently, IL-10 inactivation enhanced hepatic injury and inflammation in CX3CR1+/gfp mice receiving CCl4. Altogether, these data indicate a novel role of the CX3CL1/CX3CR1 axis in liver type 2 mHDC functions, pointing out the importance of CX3CR1 in promoting IL-10-mediated anti-inflammatory actions of HDCs.

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Role of Camphlobacter pylori and non steroidal anti-inflammatory drugs in the pathogenesis of peptic ulcer and pharmacological approaches for the treatment of peptic ulcer disease

Gastroenterology & Hepatology Open Access ◽

10.15406/ghoa.2019.10.00352 ◽

2019 ◽

Vol 10 (1) ◽

Author(s):

Amrish Kumar ◽

Mansi Verma ◽

Vipin Kumar Garg ◽

Avnesh Kumar ◽

Anjana Sharma ◽

...

Keyword(s):

Peptic Ulcer ◽

Peptic Ulcer Disease ◽

Ulcer Disease ◽

Inflammatory Drugs ◽

Anti Inflammatory

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The Role of Anti-Inflammatory Drugs in Respiratory Diseases - Pirfenidone, Penicillamine, Chloroquine and Chlorambucil

Current Respiratory Medicine Reviews ◽

10.2174/1573398x10666140526234959 ◽

2014 ◽

Vol 9 (5) ◽

pp. 334-343

Author(s):

Benjamin Courchia ◽

Aya Gozlan ◽

Maor Waldman ◽

Or Kalchiem-Dekel

Keyword(s):

Respiratory Diseases ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Pharmaceuticals ◽

10.3390/ph14070692 ◽

2021 ◽

Vol 14 (7) ◽

pp. 692

Author(s):

Ryldene Marques Duarte da Cruz ◽

Francisco Jaime Bezerra Mendonça-Junior ◽

Natália Barbosa de Mélo ◽

Luciana Scotti ◽

Rodrigo Santos Aquino de Araújo ◽

...

Keyword(s):

Inflammatory Diseases ◽

Structural Characteristics ◽

Tiaprofenic Acid ◽

Inflammatory Activity ◽

Drug Candidates ◽

Biological Target ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Privileged Structures

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

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