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

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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.

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Funding

The research that led to these results received funding from CNPQ and FAPERJ under the terms of agreements no. 573.564/2008–6 and no. E-26/170.020/2008, respectively, in addition to student support through CAPES/FAPEAL.

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Authors and Affiliations

  1. Gonçalo Moniz Institute (Fiocruz, BA), BA, 40296-710, Salvador, Brazil

    Alyne Almeida de Lima

  2. Laboratory of Catalysis and Chemical Reactivity, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil

    Geraldo José da Silva Neto

  3. Pharmacology and Immunity Laboratory, Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil

    Suellen Maria Albuquerque da Silva, Eliane Aparecida Campesatto & Magna Suzana Alexandre-Moreira

  4. Institute of Biological and Health Sciences, Federal University of Alagoas, Maceio, AL, 57072-900, Brazil

    Anderson Brandão Leite

  5. 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

    Elane Conceição dos Santos & Ênio José Bassi

  6. 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

    Aline Cavalcanti de Queiroz

  7. 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

    Eliezer Jesus Barreiro & Lidia Moreira Lima

  8. 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

    Max Denisson Maurício Viana

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  1. Max Denisson Maurício Viana
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  2. Alyne Almeida de Lima
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  12. Magna Suzana Alexandre-Moreira
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Contributions

All authors contributed to the study. Conceptualization: Max Denisson Mauricio Viana and Magna Suzana Alexandre Moreira; formal analysis, investigation, and writing of the original draft: Max Denisson Mauricio Viana; review and editing: Geraldo José da Silva Neto; experimental collaborators: Alyne Almeida de Lima, 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, and Magna Suzana Alexandre Moreira; supervision: Eliezer Jesus Barreiro, Lidia Moreira Lima, and Magna Suzana Alexandre Moreira. All authors read and approved the final manuscript.

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Correspondence to Max Denisson Maurício Viana.

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The experiments were performed after the approval by Ethics Committee-UFAL for animal handling (Protocol #041/2017).

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Viana, M.D.M., de Lima, A.A., da Silva Neto, G.J. et al. LASSBio-596: a New Pre-clinical Candidate for Rheumatoid Arthritis?. Inflammation 45, 528–543 (2022). https://doi.org/10.1007/s10753-021-01564-2

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