Erschienen in:
25.10.2021 | Original Article
LASSBio-596: a New Pre-clinical Candidate for Rheumatoid Arthritis?
verfasst von:
Max Denisson Maurício Viana, Alyne Almeida de Lima, Geraldo José da Silva Neto, Suellen Maria Albuquerque da Silva, Anderson Brandão Leite, Elane Conceição dos Santos, Ênio José Bassi, Eliane Aparecida Campesatto, Aline Cavalcanti de Queiroz, Eliezer Jesus Barreiro, Lidia Moreira Lima, Magna Suzana Alexandre-Moreira
Erschienen in:
Inflammation
|
Ausgabe 2/2022
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Abstract
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.