Effect of alpha-trinositol on carrageenan-induced rat paw edema and lowering of interstitial fluid pressure.
Alpha-trinositol attenuates edema formation and capillary albumin extravasation and lowering of interstitial fluid pressure (Pif) in several acute inflammatory reactions in rat skin or trachea. The lowering of Pif is an important driving force required to explain the rapid edema formation in acute inflammatory reactions. The lowering of Pif and edema formation are attenuated by alpha-trinositol, which is suggested to act on the cellular adhesion receptor for extracellular matrix components. This would represent a novel therapeutic strategy for acute inflammation. To further clarify the mechanisms behind the anti-inflammatory effects of alpha-trinositol, the effects of pre- and post-treatment with alpha-trinositol on edema formation and lowering of Pif were studied after subdermal injection of carrageenan in the rat. The experiments measuring Pif showed that the lowering of Pif induced by carrageenan was abolished by 10 mg alpha-trinositol when administered either prior to or after injection of 5 microl 1% (w/v) lambda carrageenan in the dorsum of the paw. Edema formation after injection of lambda carrageenan (100 microl, 1.5% w/v) into the foot pad was studied in a separate series. In control animals receiving saline vehicle, the volume of the paw injected with carrageenan increased by approximately 30% after 3-4 h. The only significant effect of infusion of 20 mg kg(-1) h(-1) alpha-trinositol was a reduction of edema to approximately 20% when treatment was started 1 h before carrageenan injection. Therefore, the plasma concentration of alpha-trinositol must already be high when carrageenan is injected in order to prevent edema in the late phase. In conclusion, the present results indicate that the mechanisms involved in the lowering of Pif in the early phase of edema development are different from those responsible for the manifest edema measured 3-4 h after carrageenan.
Reed
R K
RK
Department of Physiology, University of Bergen, Norway. rolf.reed@pki.uib.no
Westerberg
E J
EJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005110:Extracellular Space / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D018836:Inflammation Mediators; D007295:Inositol Phosphates / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D007295:Inositol Phosphates; D002351:Carrageenan; C059368:atrinositol