Pro- and anti-inflammatory actions of ricinoleic acid: similarities and differences with capsaicin.
We have investigated the pro- and anti-inflammatory effects of ricinoleic acid (RA), the main active principle of castor oil, in an experimental model of blepharitis induced by intradermal injection of carrageenan in the guinea-pig eyelid and its possible capsaicin-like mode of action on acutely dissociated rat dorsal root ganglia (DRG) neurons in vitro. Topical treatment with RA (10-100 mg/guinea-pig) or capsaicin (1-10 mg/guinea-pig) caused eyelid reddening and oedema. At lower doses (0.3-3 mg/guinea-pig and 0.009-0.09 mg/guinea-pig for RA and capsaicin, respectively) both drugs significantly potentiated the eyelid oedema induced by carrageenan. The tachykinin NK1 receptor antagonist FK 888 (0.59 mg/kg s.c.) abolished the potentiation of carrageenan-induced eyelid oedema induced by either RA or capsaicin. The neutral endopeptidase inhibitor, thiorphan (1.3 mg/kg i.v.) significantly enhanced the potentiation of carrageenan-induced eyelid oedema produced by RA. This potentiating effect was abolished by FK 888. Repeated (8 days) topical application of RA (0.9 mg/guinea-pig) or capsaicin (0.09 mg/guinea-pig) inhibited the carrageenan-induced eyelid oedema. This anti-inflammatory effect was accompanied by a reduction (75%-80% of SP and 46%-51% of NKA) in tachykinin content of the eyelids, as determined by radioimmunoassay. In dissociated rat DRG neurons, RA (0.1 mM for 5 min) significantly inhibited the inward currents induced by application of capsaicin (1 microM) and/or low pH (5.8), without inducing any currents by itself or changing voltage-dependent currents. Moreover, after 24-h incubation, RA (0.1 mM) significantly decreased the capsaicin (1 microM)-induced calcitonin gene-related peptide (CGRP) release from rat DRG neurons, whereas acute drug superfusion did not evoke CGRP release by itself. Summarizing, RA possesses capsaicin-like dual pro-inflammatory and anti-inflammatory properties which are observed upon acute and repeated application, respectively. However, unlike capsaicin, RA does not induce inward current in DRG neurons and it is devoid of algesic properties in vivo.
Vieira
C
C
Faculdade de Medicine de Riberào Preto, USP, Brazil.
Fetzer
S
S
Sauer
S K
SK
Evangelista
S
S
Averbeck
B
B
Kress
M
M
Reeh
P W
PW
Cirillo
R
R
Lippi
A
A
Maggi
C A
CA
Manzini
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D001762:Blepharitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage*; D002351:Carrageenan / Q000009:adverse effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D037102:Lectins / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D015288:Neurokinin A / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D037121:Plant Lectins; D051381:Rats; D012277:Ricinoleic Acids / Q000008:administration & dosage*; D012639:Seeds / Q000737:chemistry; D013373:Substance P / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D037102:Lectins; D010936:Plant Extracts; D037121:Plant Lectins; D012277:Ricinoleic Acids; C017707:Ricinus communis agglutinin-1; D013373:Substance P; D015288:Neurokinin A; D002351:Carrageenan; C030521:ricinoleic acid; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin