1. A clindamycin acetylated derivative with reduced antibacterial activity inhibits articular hyperalgesia and edema by attenuating neutrophil recruitment, NF-κB activation and tumor necrosis factor-α production.
- Author
-
Rodrigues FF, Lino CI, Oliveira VLS, Zaidan I, Melo ISF, Braga AV, Costa SOAM, Morais MI, Barbosa BCM, da Costa YFG, Moreira NF, Alves MS, Braga AD, Carneiro FS, Carvalho AFS, Queiroz-Junior CM, Sousa LP, Amaral FA, Oliveira RB, Coelho MM, and Machado RR
- Subjects
- Mice, Animals, Tumor Necrosis Factor-alpha pharmacology, Hyperalgesia chemically induced, Hyperalgesia drug therapy, Clindamycin therapeutic use, Clindamycin pharmacology, Neutrophil Infiltration, Zymosan, Lipopolysaccharides pharmacology, Inflammation chemically induced, Anti-Bacterial Agents pharmacology, Edema chemically induced, Edema drug therapy, NF-kappa B, Arthritis
- Abstract
We recently demonstrated that clindamycin exhibits activities in acute and chronic models of pain and inflammation. In the present study, we investigated the effects of clindamycin and a clindamycin acetylated derivative (CAD) in models of acute joint inflammation and in a microbiological assay. Joint inflammation was induced in mice by intraarticular (i.a.) injection of zymosan or lipopolysaccharide (LPS). Clindamycin or CAD were administered via the intraperitoneal route 1 h before zymosan or LPS. Paw withdrawal threshold, joint diameter, histological changes, neutrophil recruitment, tumor necrosis factor-α (TNF-α) production and phosphorylation of the IκBα and NF-κB/p65 were evaluated. In vitro assays were used to measure the antibacterial activity of clindamycin and CAD and also their effects on zymosan-induced TNF-α production by RAW264.7 macrophages. Clindamycin exhibited activity against Staphylococcus aureus and Salmonella Typhimurium ATCC® strains at much lower concentrations than CAD. Intraarticular injection of zymosan or LPS induced articular hyperalgesia, edema and neutrophil infiltration in the joints. Zymosan also induced histological changes, NF-κB activation and TNF-α production. Responses induced by zymosan and LPS were inhibited by clindamycin (200 and 400 mg/kg) or CAD (436 mg/kg). Both clindamycin and CAD inhibited in vitro TNF-α production by macrophages. In summary, we provided additional insights of the clindamycin immunomodulatory effects, whose mechanism was associated with NF-κB inhibition and reduced TNF-α production. Such effects were extended to a clindamycin derivative with reduced antibacterial activity, indicating that clindamycin derivatives should be investigated as candidates to drugs that could be useful in the management of inflammatory and painful conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF