Effect of ricinoleic acid in acute and subchronic experimental models of inflammation.
Observational studies indicate that topical application of ricinoleic acid (RA), the main component of castor oil, exerts remarkable analgesic and anti-inflammatory effects. Pharmacological characterization has shown similarities between the effects of RA and those of capsaicin, suggesting a potential interaction of this drug on sensory neuropeptide-mediated neurogenic inflammation. The aim of this study was to assess RA anti-inflammatory activities in comparison with capsaicin in several models of acute and subchronic inflammation. The acute inflammation was induced by intradermal injection of carrageenan in the mouse or by histamine in the guinea-pig eyelid. In either experiment, the extent of the oedema thickness was measured. Subchronic oedema was induced by complete Freund's adjuvant injection in the ventral right paw of mice. Tissue substance P (SP) was measured in the carrageenan experiments by radioimmunoassay (RIA). It was found that the acute topical application of RA (0.9 mg/mouse) or capsaicin (0.09 mg/mouse) significantly increased the mouse paw oedema induced by carrageenan, while an 8-day repeated topical treatment with the same doses of both compounds resulted in a marked inhibition of carrageenan-induced paw oedema matched by a reduction in SP tissue levels. Similar effects were found against histamine-induced eyelid oedema in guinea-pigs after acute or repeated application of RA or capsaicin. RA and capsaicin given for 1-3 weeks reduced the established oedema induced by Freund's adjuvant, a subchronic model of inflammation, particularly if given by the intradermal route. Either in mouse paw or in guinea-pig eyelid, capsaicin but not RA by itself produced a slight hyperemia and activation of a behavioural response (e.g. scratching of the eyelids). On the basis of the present results, RA may be seen as a new capsaicin-like, non-pungent anti-inflammatory agent suitable for peripheral application.
Vieira
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C
Department of Pharmacology, Menarini Ricerche spa, Pomezia Roma, Italy.
Evangelista
S
S
Cirillo
R
R
Lippi
A
A
Maggi
C A
CA
Manzini
S
S
D000208:Acute Disease; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D002211:Capsaicin / Q000008:administration & dosage / Q000627:therapeutic use; D002351:Carrageenan / Q000008:administration & dosage / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D005141:Eyelid Diseases / Q000188:drug therapy* / Q000276:immunology; D005143:Eyelids / Q000276:immunology; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D006168:Guinea Pigs; D006632:Histamine / Q000008:administration & dosage / Q000276:immunology; D007271:Injections, Intradermal; D008297:Male; D012277:Ricinoleic Acids / Q000008:administration & dosage / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012277:Ricinoleic Acids; D006632:Histamine; D002351:Carrageenan; D005620:Freund's Adjuvant; C030521:ricinoleic acid; D002211:Capsaicin