LASSBio-596: a New Pre-clinical Candidate for Rheumatoid Arthritis?

Autor: Viana MDM; Pharmacology and Immunity Laboratory, Institute of Biological and Health Sciences, Federal University of Alagoas, Av. Lourival Melo Mota, SN, Tabuleiro do Martins, Maceio, AL, 57072-900, Brazil. suzana.magna@gmail.com., de Lima AA; Gonçalo Moniz Institute (Fiocruz, BA), BA, 40296-710, Salvador, Brazil., da Silva Neto GJ; Laboratory of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil., da Silva SMA; Pharmacology and Immunity Laboratory, Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil., Leite AB; Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil., Dos Santos EC; Immunoregulation Research Group, Laboratory of Research in Virology and Immunology, Institute of Biological and Health Sciences, Federal University of Alagoas, AL, 57072-900, Maceio, Brazil., Bassi ÊJ; Immunoregulation Research Group, Laboratory of Research in Virology and Immunology, Institute of Biological and Health Sciences, Federal University of Alagoas, AL, 57072-900, Maceio, Brazil., Campesatto EA; Pharmacology and Immunity Laboratory, Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil., de Queiroz AC; Microbiology, Immunology and Parasitology Laboratory, Medical and Nursing Sciences Complex, Federal University of Alagoas - Campus Arapiraca, Av. Manoel Severino Barbosa - Bom Sucesso, Arapiraca, AL, 57309-005, Brazil., Barreiro EJ; Laboratory for Evaluation and Synthesis of Bioactive Substances, LASSBio®, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, PO Box 68024, Rio de Janeiro, RJ, 21944-910, Brazil., Lima LM; Laboratory for Evaluation and Synthesis of Bioactive Substances, LASSBio®, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, PO Box 68024, Rio de Janeiro, RJ, 21944-910, Brazil., Alexandre-Moreira MS; Pharmacology and Immunity Laboratory, Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2022 Apr; Vol. 45 (2), pp. 528-543. Date of Electronic Publication: 2021 Oct 25.
DOI: 10.1007/s10753-021-01564-2
Abstrakt: Pain and inflammatory disorders are significant health problems because of prevalence and associated disabilities. In this context, LASSBio-596 is a hybrid compound able to modulate TNF-α and phosphodiesterases 4 and 5, exhibiting an anti-inflammatory effect in the pulmonary inflammatory model. Aiming at a better description of the activities of LASSBio-596, we initially conducted nociception tests (acetic acid-induced abdominal writhing, glutamate, and formalin-induced nociception and hot plate test) and later inflammatory tests (acute, peritonitis; and chronic, arthritis) that directed us to this last one. In the abdominal writhing test, there was a dose-dependent inhibition, whose response occurred at the maximum dose (50 mg/kg, p.o.), used in the subsequent tests. LASSBio-596 also inhibited nociception induced by chemical (glutamate by 31.9%; and formalin, in both phases, 1st phase: 25.7%; 2nd phase: 23.9%) and thermal agents (hotplate, by increased latency for pain at two different times). These effects were independent of the motor function, legitimated in rotarod. As there was a response in the inflammatory component of nociception, we performed the peritonitis test, in which migration was inhibited by LASSBio-596 by 39.9%. As the inflammatory process is present in autoimmune diseases, we also performed the arthritis test. LASSBio-596 reduced paw edema from the 15th day to the 21st day of treatment (no liver changes and with fewer paw injuries). In addition, LASSBio-596 decreased serum levels of TNF-α by 67.1%. These data demonstrated the antinociceptive effect of LASSBio-596 and reinforces its anti-inflammatory property (i.e., RA), amplifying the therapeutic potential of this molecule.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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