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Antinociceptive and anti‐inflammatory properties of 7‐hydroxycoumarin in experimental animal models: potential therapeutic for the control of inflammatory chronic pain
Authors:Taís A De Almeida Barros  Luis AR De Freitas  José MB Filho  Xirley P Nunes  Ana M Giulietti  Glória E De Souza  Ricardo R Dos Santos  Milena BP Soares  Cristiane F Villarreal
Affiliation:1. Oswaldo Cruz Foundation, Brazil;2. State University of Feira de Santana, Brazil;3. Federal University of Paraí;4. ba, Brazil;5. Faculty of Pharmaceutical Sciences, University of S?o Paulo, Brazil;6. Hospital S?o Rafael, Bahia, Brazil;7. Faculty of Pharmacy, Federal University of Bahia, Brazil
Abstract:Objectives In the present study we investigated the antinociceptive, anti‐inflammatory and antipyretic effects of 7‐hydroxycoumarin (7‐HC) in animal models. Methods The effects of oral 7‐HC were tested against acetic acid‐induced writhing, formalin test, tail flick test, complete Freund's adjuvant (CFA)‐induced hypernociception, carrageenan‐induced paw oedema, lipopolysaccharide‐induced fever and the rota rod test. Key findings 7‐HC (3–60 mg/kg) produced a dose‐related antinociception against acetic acid‐induced writhing in mice and in the formalin test. In contrast, treatment with 7‐HC did not prevent thermal nociception in the tail flick test. A single treatment with 7‐HC, 60 mg/kg, produced a long‐lasting antinociceptive effect against CFA‐induced hypernociception, a chronic inflammatory pain stimulus. Notably, at 60 mg/kg per day over 4 days the administration of 7‐HC produced a continuous antinociceptive effect against CFA‐induced hypernociception. 7‐HC (30–120 mg/kg) produced anti‐inflammatory and antipyretic effects against carrageenan‐induced inflammation and lipopolysaccharide‐induced fever, respectively. Moreover, 7‐HC was found to be safe with respect to ulcer induction. In the rota rod test, 7‐HC‐treated mice did not show any motor performance alterations. Conclusions The prolonged antinociceptive and anti‐inflammatory effects of 7‐HC, in association with its low ulcerogenic activity, indicate that this molecule might be a good candidate for development of new drugs for the control of chronic inflammatory pain and fever.
Keywords:7‐hydroxycoumarin  antiinflammatory  antinociception  antipyretic  chronic pain  gastric toxicity
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