The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis

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Camargo, Livia L. ^{[1, 2]} ; Denadai-Souza, Alexandre ^{[2, 3, 4]} ; Yshii, Lidia M. ^{[2, 3, 5, 6]} ; Lima, Carla ^[7] ; Teixeira, Simone A. ^[2] ; Cerqueira, Anderson R. A. ^[2] ; Gewehr, Mayara C. F. ^[2] ; Fernandes, Elizabeth S. ^{[8, 9]} ; Schenka, Andre A. ^[10] ; Muscara, Marcelo N. ^[2] ; Ferro, Emer S. ^{[2, 11]} ; Costa, Soraia K. P. ^[2]

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^[1] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark - Scotland

^[2] Univ Sao Paulo, Dept Pharmacol, Biomed Sci Inst ICB I, BR-05508900 Sao Paulo, SP - Brazil

^[3] Univ Toulouse, INSERM UMR U1043 CNRS U5282, Ctr Physiopathol Toulouse Purpan, UPS, F-31300 Toulouse - France

^[4] Katholieke Univ Leuven, Dept Chron Dis Metab & Ageing, Translat Res Ctr Gastrointestinal Disorders, Lab Intestinal Neuroimmune Interact, Leuven - Belgium

^[5] VIB Ctr Brain & Dis Res, Leuven - Belgium

^[6] Katholieke Univ Leuven, Dept Microbiol & Immunol, Leuven - Belgium

^[7] Butantan Inst, Special Lab Appl Toxicol CAT CEPID, Ave Vital Brazil 1500, BR-05503009 Sao Paulo, SP - Brazil

^[8] Inst Pesquisa Pele Pequeno Principe, BR-80250060 Curitiba, PR - Brazil

^[9] Fac Pequeno Principe, Programa Posgrad Biotecnol Aplicada Saude Crianca, BR-80230020 Curitiba, PR - Brazil

^[10] Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Campinas - Brazil

^[11] Weizmann Inst Sci, Dept Regulat Biol, IL-7610001 Rehovot - Israel

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 890, JAN 5 2021.
• Citações Web of Science: 0

Resumo

Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuminflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1 beta, tumor necrosis factor-alpha and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 mu g/clay, i.art.), Hp given orally (20 mu g/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i. p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive monoarthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 mu g/knee) or p.o. (20 mu g/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P < 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P < 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL1 beta, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP. (AU)

• Processo FAPESP: 16/04000-3 - Farmacologia de oligopeptidases e peptídeos intracelulares
• Beneficiário: Emer Suavinho Ferro
• Modalidade de apoio: Auxílio à Pesquisa - Temático