Free and nanoencapsulated vitamin D3 : effects on E-NTPDase and E-ADA activities in an animal model with induced arthritis.
The effect of vitamin D3 in oral solution (VD3 ) and vitamin D3 -loaded nanocapsules (NC-VD3 ) was analysed in animals with complete Freund's adjuvant (CFA) induced arthritis (AR). For this purpose, we evaluated scores for arthritis, thermal hyperalgesia and paw oedema, as well as histological analyses and measurements of the activity of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) enzymes in rat lymphocytes. Haematological and biochemical parameters were also determined. The doses administered were 120 UI/day of VD3 and 15.84 UI/day of NC-VD3 . Fifteen days after the induction of AR, the groups were treated for 15 days with vitamin D3 . The results demonstrated that VD3 was able to reduce arthritis scores, thermal hyperalgesia and paw oedema in rats with CFA-induced arthritis. However, treatment with NC-VD3 did not reduce arthritis scores. The histological analyses showed that both formulations were able to reduce the inflammatory changes induced by CFA. The activity of E-NTPDase in rat lymphocytes was higher in the AR compared with the control group, while the activity of E-ADA was lower. This effect was reversed after the 15-day treatment. Data from this study indicates that both forms of vitamin D3 seem to contribute to decreasing the inflammatory process induced by CFA, possibly altering the activities of ectoenzymes. Copyright © 2016 John Wiley & Sons, Ltd.


CONCLUSIONS
The effects promoted by both formulations of vitamin D3 , either in oral solution or nanoencapsulated form, strongly suggests the softening of the inflammatory process induced by complete Freund's adjuvant (CFA), possibly altering the E-NTPDase and E-ADA activities. However, it is known that vitamin D has a beneficial effect on the modulation of the immune system components responsible for the inflammatory process. Moreover, the establishment of responses to treatment with vitamin D3 may provide an alternative for inhibiting the proinflammatory response, assisting in our understanding of the immunopathology of this disease and possibly improving the signs and symptoms that hinder the quality of life of patients with rheumatoid arthritis.


CONCLUSIONS
Evaluation of the effects on the E-NTPDase and E-ADA activities in an animal model of induced arthritis. Two formulations of vitamin D3 were used: form oral solution and nanoencapsulated. Vitamin D3 seems to contribute to the inflammatory process induced by CFA. Vitamin D3 possibly alters the E-NTPDase and E-ADA activities. Vitamin D3 may be an alternative supplementary treatment for chronic arthritis.
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Karine Lanes
KL
da Silveira
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Leonardo Lanes
LL
da Silveira
Centro de Ciências Naturais e Exatas, Programa de Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Maria Luiza Prates
ML
Thorstenberg
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Fernanda Licker
FL
Cabral
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Livia Gelain
LG
Castilhos
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
João Felipe Peres
JF
Rezer
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Diego Fontana
DF
de Andrade
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Ruy Carlos Ruver
RC
Beck
Hospital Veterinário Universitário, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Heloísa
H
Einloft Palma
Hospital Veterinário Universitário, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Cinthia Melazzo
CM
de Andrade
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Renata da Silva
Rda S
Pereira
Centro de Ciências da Saúde, Departamento de Patologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Nara Maria Beck
NM
Martins
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Claudia de Mello
Cde M
Bertonchel Dos Santos
Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.|Centro de Ciências Naturais e Exatas, Programa de Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Daniela Bitencourt Rosa
DB
Leal
D000243:Adenosine Deaminase / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002762:Cholecalciferol / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology; D053769:Nanocapsules / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D017208:Rats, Wistar; D012996:Solutions
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D053769:Nanocapsules; D012996:Solutions; D002762:Cholecalciferol; D005620:Freund's Adjuvant; D000243:Adenosine Deaminase; D001081:Apyrase; C067869:CD39 antigen
CFA; E-ADA; E-NTPDase; arthritis; lymphocytes; vitamin D3