ABSTRACT
Urticaria is induced by the histamine released from mast cells which develops wheals (edema) as a visual feature. In clinical practice, second-generation histamine H1 -receptor blockers are routinely used as the first-line symptomatic treatment for urticaria. Nevertheless, not much research has directly examined the second-generation histamine H1-receptor blockers' ability to reduce edema. In this study, we directly evaluated the anti-edematous activities of three second-generation histamine H1-receptor blockers available in the market (epinastine hydrochloride, cetirizine hydrochloride, and levocetirizine hydrochloride) using a λ-carrageenan-induced footpad edema model. One hour before the induction of edema with 1% λ -carrageenan injection, all second-generation histamine H1 -receptor blockers (5, 10, 50 and 100 mg/kg) were subcutaneously administered to rats. At 0.5 and 3 hours after λ -carrageenan administration, the edema volume was evaluated using a Plethysmometer. Epinastine hydrochloride significantly suppressed the edema growth in a dose-dependent manner. Cetirizine hydrochloride showed a slight anti-edematous effect, while levocetirizine significantly inhibited the development of edema in a dose-dependent manner. On the other hand, dextrocetirizine did not prevent edema from growing. In summary, second-generation histamine H1 -receptor blockers, at least those examined in this study, may be able to reduce the clinical symptoms of urticaria associated with edema. Levocetirizine hydrochloride is also anticipated to have stronger anti-edematous effects than cetirizine hydrochloride because levocetirizine is responsible for cetirizine's anti-edematous activity.
Subject(s)
Carrageenan , Cetirizine , Edema , Animals , Cetirizine/pharmacology , Edema/drug therapy , Edema/chemically induced , Rats , Male , Stereoisomerism , Histamine H1 Antagonists/pharmacology , Histamine H1 Antagonists, Non-Sedating/pharmacology , Dose-Response Relationship, Drug , Rats, Wistar , Imidazoles/pharmacology , Rats, Sprague-Dawley , DibenzazepinesABSTRACT
Some macrolide antibiotics, which share a basic lactone ring structure, also exhibit anti-inflammatory actions in addition to their antibacterial activities. However, no study has directly compared anti-inflammatory effects on acute inflammation among macrolide antibiotics with the distinct size of the lactone ring. In this study, we evaluated and compared the anti-inflammatory activities of four 14-membered macrolides (erythromycin, clarithromycin, roxithromycin, oleandomycin), one 15-membered macrolide (azithromycin), and three 16-membered macrolides (midecamycin, josamycin, leucomycin) using a rat carrageenan-induced footpad edema model. All macrolide antibiotics were intraperitoneally administered to rats one hour before the induction of inflammatory edema with 1% λ -carrageenan. The anti-inflammatory effects on acute inflammation were evaluated by changing the edema volume. All 14-membered and 15-membered macrolide antibiotics significantly suppressed the development of edema. Conversely, none of the 16-membered macrolide antibiotics inhibited the growth of edema. In conclusion, compared to 16-membered macrolide antibiotics, 14-membered and 15-membered macrolide antibiotics have stronger anti-inflammatory effects. Further research should be done to determine why different lactone ring sizes should have distinct anti-inflammatory effects.
Subject(s)
Anti-Bacterial Agents , Anti-Inflammatory Agents , Carrageenan , Edema , Inflammation , Macrolides , Animals , Macrolides/pharmacology , Rats , Edema/drug therapy , Edema/chemically induced , Male , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Inflammation/drug therapy , Inflammation/chemically induced , Disease Models, Animal , Rats, Sprague-Dawley , Anti-Inflammatory Agents, Non-Steroidal/pharmacologyABSTRACT
Arylpropionic acid nonsteroidal anti-inflammatory drusg (NSAIDs) primarily bind to subdomain III A (site II) of human serum albumin (HSA). Ketoprofen (KP), an arylpropionic acid that contains a photoreactive benzophenone moiety, was used to photolabel the binding region of site II. LC/Q-TOF mass spectrometry determination revealed that R485 was the amino acid residue that formed covalent adduct with the benzophenone moiety of KP. Point mutation of arginine 485 to alanine showed a slight decrease in the overall binding percentage of KP when compared to that of native HSA. The induced circular dichroism spectral data of KP with both R485A and native albumin confirmed the photolabeling findings. Interestingly, an increase in the extent of [14C]KP covalent adduct formation with the 11.6 kDa peptide derived from subdomain IIB-IIIA was observed for R485A. In contrast, mutation of arginine 410 caused a significant reduction of binding percentage, confirming the importance of this residue in high affinity binding of arylpropionic acid derivatives. This may indicate that while KP's carboxylate interacts electrostatically with arginine 410, the benzophenone moiety may have swung away from helix 6 in the absence of arginine 485. In this study, photolabeling of native and mutants albumins, R485A and R410C with [14C]KP confirmed that R485 involved in the non-electrostatic interaction with the benzophenone moiety of KP, but not vital to hold KP in the binding pocket of subdomain IIIA.
