Release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid and cysteinyl-leukotrienes in carrageenin-induced inflammation: Effect of non-steroidal anti-inflammatory drugs

Abstract

Inflammatory exudates obtained in rats after subcutaneous implantation of carrageenin-soaked sponges were found to contain relatively large amounts of 15-hydroxy-5,8,11, 13-eicosatetraenoic acid (15-HETE) and smaller amounts of cysteinyl-leukotrienes (LT) in addition to LTB4, thromboxane (TX) B2 and prostaglandin (PG)E2. Concentrations of 15-HETE and cysteinyl-LT were high 5 hours after sponge implantation and decreased significantly within 24 hours. This time-course, which is similar to that of TXB2, but differs from that of PGE2, suggests migrating leukocytes as a major source of 15-HETE and cysteinyl-LT. Aspirin, sodium salicylate, dipyrone (100 mg/kg each) and indomethacin (2 and 20 mg/kg) decrease the concentrations of cyclooxygenase products of arachidonate metabolism, but did not significantly affect levels of 15-HETE. Cysteinyl-LT were increased by 20 mg/kg indomethacin, but remained unaffected by 2 mg/kg indomethacin and by the other non-steroidal anti-inflammatory drugs (NSAID) tested. 15-HETE and cysteinyl-LT could play a mediator role in inflammation. In addition, they could modulate the release and effects of other inflammatory mediators.

Effect of total phenolics from Laggera alata on acute and chronic inflammation models

“…derived mediators (Oh-ishi et al, 1989;Dawson et al, 1991;Peskar et al, 1991;Cuzzocrea et al, 1997). In addition to oxyradicals, overproduction of NO also plays an important role in various models of inflammation (Moncada et al, 1991;Nanthan, 1996;Cuzzocrea et al, 1998).…”

Inducible Nitric Oxide Synthase—Knockout Mice Exhibit Resistance to Pleurisy and Lung Injury Caused by Carrageenan

“…It appears that the early phase (1 to 2 h) of carrageenan-induced inflammation is related to the production of histamine, leukotrienes, and platelet-activating factor, whereas the delayed phase (4 to 24 h) of the carrageenan-induced inflammatory response has been linked to neutrophil infiltration and the production of neutrophil-derived free radicals, such as hydrogen peroxide, superoxide, and hydroxyl radical, as well as to the release of other neutrophil-derived mediators (14,(22)(23)(24)(25)(26). The role of ROS in the pathophysiology of inflammation is well established.…”

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models

“…The Hargreaves model[2526] was also used to evaluate the effect of XAE and XA on thermal hyperalgesia. Carrageenan-induced inflammatory pain is well-known to involve inflammatory mediators like cyclooxygenase products (PGE 2 ), leukotrienes, mast cells products (histamine, 5-HT), neuropeptides, cytokines (IL-1β and TNFα), nitric oxide, nerve growth factor (NGF), and transcription factors (nuclear factor-kappa B; NF-κB),[49–52] which are released as a result of tissue injury. Most of these mediators (especially prostaglandins) sensitize peripheral nociceptors to noxious stimuli and subsequently release other mediators in spinal cord, resulting in thermal and mechanical hyperalgesia.…”