Effects Of Several Anti-inflammatory Drugs Research Articles

Clarithromycin inhibits TNF-α-induced MUC5AC mucin gene expression via the MKP-1-p38MAPK-dependent pathway

Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases. It was recently reported that MKP-1 appears to mediate the effects of several anti-inflammatory drugs, including glucocorticoids, but the role of MKP-1 on mucin gene expression in the presence of macrolides in the human airway remains unknown. Here, we demonstrate that the MKP-1 protein is induced by clarithromycin and that clarithromycin suppresses TNF-α-induced MUC5AC mucin gene expression in a p38 MAPK-dependent manner in human airway epithelial (NCI-H292) cells. Our study thus provides new insights into the role of MKP-1 in mediating the effects of macrolides and may help in the development of new therapeutic strategies against mucin overproduction.

Spasmolytic and calmodulin inhibitory effect of non-steroidal anti-inflammatory drugs in vitro

The effect of several anti-inflammatory drugs (NSAIDs), the calmodulin inhibitor W-7 and cortisol on vanadate-induced tonic contraction and on calmodulin dependent cAMP-phosphodiesterase activity have been assayed. Indomethacin, diclofenac, phenylbutazone, mefenamic acid, naproxen, tolmetin, piroxicam, aspirin and W-7, but not metimazol, produce dose-dependent relaxation of vanadate-induced tonic contraction on isolated rat uterus. Cortisol relaxes the vanadate contraction up to 45%. None of the drugs assayed inhibit the basal activity of phosphodiesterase with concentrations lower than 1 mM. However, indomethacin, diclofenac, phenylbutazone, mefenamic acid, naproxen, piroxicam, aspirin and W-7 inhibit, in a concentration-dependent way, the calmodulin-stimulated activity of phosphodiesterase. The maximum inhibition achieved with tolmetin (1 mM) and cortisol (1 mM) was 38% and 24%, respectively. Metamizol has no effect on basal or/and stimulated phosphodiesterase. This, as far as we know, is the first description of relationship between NSAIDs and calmodulin-dependent processes and our results suggest that the inhibition of calmodulin with NSAIDs may be directly related to their pKa and liposolubility.

Effects of several anti-inflammatory drugs on cadmium-induced inflammation in rat testis

To investigate the effect of several anti-inflammatory drugs on cadmium-induced inflammation in the testis of rat, the degree of intratesticular hemorrhage and lipoperoxide level in the testis were measured as a parameter of the inflammation. Alpha-tocopherol and coenzyme Q10which are well known as antioxidative agents had a potent antiinflammatory effect on cadmium-induced inflammation in rat testis. On the other hand, indomethacin and peonol which are supposed to be potent inhibitors of cyclooxygenase activity and prostaglandin synthesis, enhanced cadmium-induced intratesticular hemorrhage in a dose dependent manner. As for glucocorticoid (predonin) which has been reported to be an inhibitory protein on phospholipase A2activity, a moderate inhibitory effect on inflammatory changes in rat testis induced by cadmium was observed although it was statistically not significant. These results suggest that oxidative and inflammatory reaction induced by cadmium in rat testis may be considered not to be promoted by the accerelation of cyclooxygenase pathway in arachidonic acid cascade, but by the accerelation of lipoxygenase pathway or radical reaction mediated oxygenation of nonesterified polyunsaturated fatty acids, which has been reported to be increased in the inflammation in the testis of rat induced by cadmium.

Effects of several anti-inflammatory drugs on the various parameters involved in the inflammatory response in rat carrageenin-induced pleurisy

In rat carrageenin pleurisy, both steroidal and non-steroidal anti-inflammatory drugs (SAID and NSAID respectively) produced a dose-related reduction of exudate volume and of prostaglandin (PG)E 2 contents in the exudate at 3 h after carrageenin. However, with the exception of ketoprofen, administration of all the NSAID in low doses resulted in a significant reduction of PGE 2 contents with no significant reduction in exudate volume. NSAID reduced leucocyte number and total activities of lysosomal enzymes in the exudate at 3 h after carrageenin only at the higher doses, while SAID did so in a dose-related manner. Both SAID and NSAID reduced the arylsulfatase activity released into the exudate (free activity) dose-relatedly but not the free activity of β-glucuronidase at 3 h after carrageenin. However, some drug treatments resulted in a lower reduction in free arylsulfatase activity than in exudate volume. These results suggest that the reduction of PGE 2 contents may be the main contribution to the anti-exudative activities of anti-inflammatory drugs in rat carrageenin pleurisy and that this effect may be complemented by the reduction of free activity of lysosomal enzymes such as arylsulfatase.

Effect of several anti-inflammatory drugs on PG production, PMN cells migration and release of lysosomal enzymes in rat carrageenin pleurisy

Effect of several anti-inflammatory drugs on PG production, PMN cells migration and release of lysosomal enzymes in rat carrageenin pleurisy

Clamping Method as Inflammation Model

In order to investigate the usefulness of the clamping method as an inflammation model, the healing process of clamp-induced gastric muco-muscular defects in rats were observed. Furthermore, the effects of several antiinflammatory drugs on the healing process were studied quantitatively.Male Wistar rats weighing 200-250 gm. were used. An acute gastric muco-muscular defect was produced with a special 12 × 4 mm metal clamp applied for 24 hours. Tested drugs were given 7 days after clamping.Histological findings showed inflammations such as submucosal edema, and infiltration of polymorpho-nuclear cells in the margin of the mucosal defect in the early phase while granulation was observed in the base of the mucosal defect in the late phase.The tested anti-inflammatory drugs adversely influenced the gastric muco-muscular defect in the following ways. Cortisone acetate inhibited mucosal regeneration and granulation while prednisolone and indomethacine inhibited only the mucosal regeneration. Aspirin and phenylbutazone inhibited regeneration to a lesser degree. D-penicillamine didn't have any adverse effects on either regeneration or granulation.The clamping method is useful as an inflammation model as well as a way to check the adverse effects of anti-inflammatory drugs.

Corticosteroids inhibit prostaglandin production by rheumatiod synovia.

PROSTAGLANDIN synthesis is inhibited by a wide variety of non-steroid anti-inflammatory drugs, and it has been suggested that the pharmacological effects of these drugs may be attributed to their inhibition of prostaglandin (PG) biosynthesis1,2. Although corticosteroids are among the most potent anti-inflammatory agents available, they lack inhibitory effects on PG synthesis in many systems3–6. We have investigated the effects of several anti-inflammatory drugs on PG production by rheumatoid synovial tissue in vitro. Non-steroidal agents inhibit PG synthesis by the synovia and their order of effectiveness is similar to that seen in other tissues7. Adrenocorticosteroids are also potent inhibitors of PG production by rheumatoid synovia, and the results of these experiments are reported here.