Improvement of Resveratrol Effects When Combined with Rice Oil in Rat Models of Inflammation
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This study investigated the effects of systemic treatment with a new formulation of resveratrol (RSV) vehicled in rice oil (RSVO) in experimental rat models of inflammation. Male Wistar rats were evaluated in the following in vivo models: carrageenan-induced acute edema, complete Freund’s adjuvant (CFA)-evoked sub-chronic edema, and CFA-induced polyarthritis. The animals were treated orally with RSVO (10–15 mg/kg) or RSV (100–200 mg/kg), depending on the experimental protocol. RSV was more effective than RSVO in carrageenan-elicited acute edema when dosed in either prophylactic or therapeutic schemes of administration. However, the repeated RSVO administration, at 10-fold lower doses, exhibited superior anti-inflammatory actions in either the sub-chronic edema or the chronic polyarthritis model elicited by CFA, when compared with RSV. The novel formulation RSVO displayed a lower plasma biotransformation when compared with the RSV-treated group—46% versus 88% of metabolites, respectively. RSVO also prevented polyarthritis-related cartilage destruction, an effect that might rely on the inhibition of the pro-inflammatory cytokine interleukin-6 (IL-6), associated with an increase of the anti-inflammatory cytokine interleukin-10 (IL-10). Noteworthy, the long-term administration of RSVO did not elicit any gastrointestinal harm. Our study revealed that RSVO was notably effective in the long-term inflammatory and degenerative responses triggered by CFA. This innovative formulation might well represent a promising alternative for treating chronic inflammatory diseases, such as arthritis.
KEY WORDSacute and chronic inflammation polyarthritis complete Freund’s adjuvant resveratrol resveratrol vehicled in rice oil
We would like to thank Mr. Juliano Soares and Mrs. Janaína Pasetti Nunes for their excellent technical assistance. Our work was supported by Financiadora de Estudos e Projetos (FINEP, Brazil) research grant “Implantação, Modernização e Qualificação de Estrutura de Pesquisa da PUCRS” (PUCRSINFRA) # 01.11.0014-00. Rodrigo B. M. Silva is postdoctoral fellowship receiving grants from National Institute of Science and Technology in Tuberculosis (INCT-TB). Maria M. Campos is a researcher career awardee of Conselho Nacional de Ciência e Tecnologia (CNPq; 304042/2018-8). Fernanda B. Morrone is a researcher career awardee of Conselho Nacional de Ciência e Tecnologia (CNPq; 310317/2018-5).
Compliance with Ethical Standards
The Institutional Animal Ethics Committee approved all the experimental protocols used in the present study.
Conflict of Interest
The authors declare that they have no conflicts of interest.
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