Ml Of Carrageenan Research Articles

Anti-inflammatory effects of oral cannabidiol in rat models

Background: Cannabidiol (CBD), a non-psychoactive compound in cannabis, has various pharmacological advantages associated with clinical use, especially for reducing inflammatory arthritis and paw edema in animal models. This study evaluated the anti-inflammatory effects of various oral CBD doses (5-40 mg/kg) in rats after injecting 0.1 mL of carrageenan. Methods: Rats were orally administered various CBD doses an hour before the carrageenan-induced inflammation to observe the anti-inflammatory effects of CBD. Paw edema was measured at 0, 1, 2, 3, 4, and 5 h after carrageenan induction. Following a six-hour induction of carrageenan, histological analysis employing hematoxylin and eosin staining was performed to investigate inflammatory cell infiltration at paw edema. In addition, blood samples were taken and used for cytokine detection using ELISA and bead-base assays. Results: We found that the efficacy of all oral CBD doses decreased paw edema and was comparable to or had greater efficacy than an anti-inflammatory agent (Diclofenac 10 mg/kg), especially at 2, 3, 4, and 5 h after induced paw edema. Moreover, a high dose (40 mg/kg) of CBD suppressed chemokine productions, including monocyte chemoattractant protein (MCP)-1 and MCP-3, compared to diclofenac and placebo. In addition, serotonin levels, a pro-inflammatory-like neurotransmitter, were drastically decreased in rats treated with either CBD or diclofenac. Conclusions: Oral CBD is an interesting anti-inflammatory agent for use in the clinical setting. However, more information regarding drug safety and efficacy in a large population of human studies is needed.

Antioedematogenic and anti-inflammatory actions of Phragmanthera incana (Schum) Balle leaf in carrageenan-induced inflammation models in rats

Phragmanthera incana (Schum) is a specie of mistletoe that has been mentioned in Nigeria ethnomedicine to be used in the treatment of inflammatory disorders. The aim of this study was to investigate the anti-inflammatory effect of Phragmanthera incana leaf ethanol extract (PIEE) in carrageenan-induced inflammation models in rats. In the carrageenan-induced rat paw oedema experiment, 0.1 mL of carrageenan (1%) was injected into the paw one hour after treatment with PIEE (125, 250 and 500 mg/kg). Paw volume was measured hourly for 4 h using the plethysmometer. The anti-inflammatory activity was investigated using the carrageenan-induced air pouch inflammation model. Leucocytes migration and pro-inflammatory mediators (TNF-α and IL-6) were evaluated in the air pouch exudate. Oxidative stress biomarkers (MDA, Nitrite, GSH and Catalase) were estimated in both the carrageenan-induced paw tissue homogenates and air pouch exudate. PIEE (125, 250 and 500 mg/kg) administration significantly (p < 0.05) reduced paw oedema hourly post-carrageenan injection. PIEE administration displayed dose-dependent significant (p < 0.05) reduction in fluid exudates and total leucocytes counts respectively. The extract administration also decreased elevated pro-inflammatory cytokines (TNF-α and IL-6) levels respectively. PIEE administration demonstrated antioxidant activity by attenuating carrageenan-induced increase in malondialdehyde and nitrite as well as decrease in reduced glutathione and catalase levels in rats. Phragmanthera incana leaf ethanol extract possess anti-inflammatory properties, suggesting protective function in inflammatory diseases.

In vivo anti-inflammatory activity and UPLC-MS/MS profiling of the peels and pulps of Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus

Ethnopharmacological relevanceCucumis melo var. cantalupensis and Cucumis melo var. reticulatus are the most famous varieties of netted muskmelon or cantaloupe in Egypt. Cantaloupe has a great reputation as an anti-inflammatory drug for hot inflammation of liver, cough, eczema, and kidney disorders such as ulcers in the urinary tract, and our objective was to confirm this use scientifically. Materials and methodsInflammation was induced in adult male Sprague Dawley rats by subcutaneous injection of 0.05 ml of carrageenan (1% solution in saline) into the plantar surface of the right hind paw 30 min after oral pretreatment of the rats with 95% ethanolic extracts of Cucumis melo var. cantalupensis peels (CCP) and pulps (CCU) and Cucumis melo var. reticulatus peels (CRP) and pulps (CRU) at doses of 25 and 50 mg/kg. Indomethacin (10 mg/kg) was used as a standard drug. The effect of the tested samples was measured on the oedema volume, as well as PGE-2, TNF-α, IL-6 and IL-1β levels. Metabolic profiling of the extracts was performed using UPLC-MS/MS analysis. ResultsPretreatment of rats with the ethanol extract of the pulps and peels of the two varieties at doses of 25 and 50 mg/kg significantly inhibited the carrageenan-induced increase in the oedema volume of the rat paws after 3 h, except for the low dose of the French cantaloupe pulp. CRP at 50 mg/kg caused the most significant reductions in both TNF-α (P < 0.05) and IL-1β (P < 0.001) levels, while CCP caused the most significant reductions in PGE-2 and IL-6 (P < 0.05) levels. Increases in PGE-2, TNF-α, IL-6 and IL-1β levels were also significantly prevented by indomethacin (10 mg/kg). UPLC-MS/MS facilitated the identification of 44 phenolic compounds, including phenolic acids and flavonoids. ConclusionThis is the first report of the chemical and biological study of the peels of Cucumis melo var. cantalupensis and Cucumis melo var. reticulatus.

ANTI-INFLAMMATORY AND ANALGESIC ACTIVITY OF CURCUMIN WITH DIFFERENT NSAIDS

The objective of this study was to investigate the anti-inflammatory and analgesic activity of curcumin with combination of different drugs using carrageenan induced paw edema model and writhing test in mice. Nimesulide and tenoxicam were administered orally at different doses of 2.5, 5.0 and 7.5 mg/kg and the lower doses of these drugs were also administered orally with curcumin 60 mg/kg. After, 1 hour 0.1 ml of carrageenan (i.e. 10 mg/ml) was injected into the sub-plantar region of right hind paw of the Wistar Albino rats (150-200g) and paw volume was measured after 30 mins 1 hr, 2 hr and 3 hr using a Plethysmometer. In analgesic activity, the drug ketorolac was used with combination of curcumin and number of writhes induced by glacial acetic acid administration in mice were observed. Administration of carrageenan produced significant edema in the hind paw of rats. The edema was found to be significantly inhibited by combination of curcumin 60 mg/kg and the lower doses of nimesulide &amp; tenoxicam in different time interval and having comparable effects as of higher doses of these drugs. Similar results were also observed in analgesic activity. From this study it can be concluded that curcumin having synergistic effect when administered with combination different anti-inflammatory and analgesic agents.

ACUTE AND SUBACUTE ANTI-INFLAMMATORY ACTIVITIES OF DICHLOROMETHANE EXTRACT OF CASSIA ALATA (LINN.) LEAVES IN WISTAR RATS

Background: In Burkina Faso, leaves of Cassia alata are used in the treatment of several diseases, including inflammation. This study evaluated the anti-inflammatory effects of the dichloromethane extract of Cassia alata leaves (CF-AECal) on different models of inflammation in wistar rats in order to enhance its use in traditional medicine. &#x0D; Materials and Methods: Acute inflammation was induced among rats with 0.1 ml of carrageenan, serotonin, histamine and dextrane 1%. The effects of the CF-AECal 50 mg/kg and 100 mg/kg were compared to the effects of diclofenal 5 mg/kg, prednisone 5 mg/kg, promethazine 1 mg/kg, cyproheptadin 2 mg/kg. Cotton pellet and air pouch - induced granuloma permitted to study CF-AECal effects on the subacute inflammation. The ways of administrations were intra peritoneal for the substances of inductions and oral for the molecules of references and CF-AECal. &#x0D; Result: Carrageenan-induced paw edema has been inhibited to 52.39% by CF-AECal 50 mg/kg and 50.17% by CF-AECal 100 mg/kg. Wet granulomas formation has been inhibited by CF-AECal 50 and 100 mg/kg to 20.94 and 57.82%. The dry granulomas were inhibited at 24.32 and 59.04% by CF-AECal 50 and 100 mg/kg. Air pouch fluid was significantly reduced by CF-AECal in comparison to the control group. There was a massive recruitment of leukocytes in the pocket granuloma of the control group. CF-AECal caused strong inhibition of this infiltration of leukocytes (p&lt; 0.001). &#x0D; Conclusion: Dichloromethane extract of Cassia alata showed anti-inflammatory effects.

The aspects of free radical oxidation in the lungs of rats with pleurisy under long-term lighting

Introduction.Pathological changes in human body due to light exposure at night are triggered by circadian disruption, inhibition of melatonin secretion by the pineal gland at night that leads to its reduction in blood. Clinical and experimental data indicate high importance of free radical oxidation inthe pathogenesis of pulmonary diseases. The aim of the study – to explore the influence of a melatonin deficiencyin addition to pleurisy on free radical oxidation in the tissues of the lungs of rats exposed to light for 30 days.Research Methods. Experiments were carried out on male albino Wistar rats. The animals were randomized into four groups with 7 animals in each: an intact group, 30 day pineal gland hypofunction, carrageenan pleurisy, 30 day pineal gland hypofunction with carrageenan pleurisy. Pineal gland hypofunction was modeled by 1500 lx fluorescent lamps around the clock. The experimental pleurisy was induced in anesthetized animals by intrapleural injection of 0.1 ml of carrageenan. Superoxide (•О2-) products were determined by the reaction with nitro blue tetrazolium under the influence of NADH, NADP and pirogenal. The concentration of diene conjugates was determined by I.D. Stalna technique, TBA-active products – by I.D. Stalna, T.H. Harishvili method, trienes, ketodienes, - by a modified method based on the molar extinction coefficient.Results and Discussion.Assessingthe intensity of the reactive oxygen species (ROS) generation, a significantincrease of the •О2-level in all sources of its generation in the tissues of the lungs has been observed both in the control group with pleurisy and in the rats with 30-day pineal gland hypofunctionandpleurisy, compared to the intact animals.The chronic pineal gland hypofunction in the animals with experimental pleurisy lead to •О2- generationby the microsomal electron transport chain (ETC) by 54.6 % (р&lt;0.05) when compared with carrageenan group of rats. No significant changes in concentration of the lipid peroxidation products has been observed in the animals with pleurisy during long-term light exposure.Conclusions. Chronic hypofunction of the pineal gland with the carrageenan-induced pleurisy causes activation of the free radical processes in the rats’ lung tissues and occur as hyperproduction of the superoxide anion radical by the microsomal chain of oxidation. This fact denotes probable abnormalities in the function of the microsomal electron transport chains especially under the condition change of properties of dehydrogenases.

POTENTIAL ANTI-INFLAMMATORY ACTIVITY OF PLUMBAGO ZEYLANICA

Objective: To determine the anti-inflammatory activity of dichloromethane extract of Plumbago zeylanica (DMEPZ), and its possible mechanism of action.Methods: Male Wistar rats (180-200 g) under controlled standard conditions (24±1°C, 55-58 humidity and 12 hrs light/dark cycle). The groups were divided into 5 groups (n=6/group) and assigned as positive control, negative control, and standard and two different test dose groups of P. zeylanica. Paw edema induced by subplantar injection of 0.1 mL of carrageenan (suspended in 1% carboxymethyl cellulose) into the right hind paw in all groups except negative control group. Granuloma induced by cotton pellets (10±1 mg) were implanted into groin region of each rat. The groups were divided into 4 groups (n=6/group) and assigned as possitive control, two different test dose groups of P. zeylanica and standard.Results: Oral administration of DMEPZ shown a significant (p&lt;0.05) dose-dependent protection against carrageenan-induced paw edema. At 1st hr, P. zeylanica shown an inhibition effect of edema in the different doses of 250 mg/kg and 500 mg/kg were found to be 28.57 and 31.79%, respectively. At 3rd hrs, the paw edema inhibition was found to be 30.70 and 40.15%, respectively. Diclofenac (25 mg/kg) had effect of 34.10 and 41.73% (p&lt;0.001) inhibition of paw edema at in 1 and 3 hrs. P. zeylanica 500 mg/kg showed percentage inhibition of wet and dry cotton pellet granuloma in rats 55.84% and 47.92%, respectively.Conclusion: Thus, the present study revealed that the DMEPZ offered significant protection against inflammation.

Uji Aktivitas Anti-Inflamasi Minyak Atsiri Daun Kemangi (Ocimum americanum L.) pada Tikus Putih Jantan yang Diinduksi Karagenan

Kemangi (Ocimum americanum L.) is an aromatic plant that contains citral and known as anti-inflammatory agent. The aim of this study was to determine the anti-inflammatory activity of the essential oil kemangi leaves (Ocimum americanum L.) on carrageenan-induced rat. The male rats were divided into six groups, each consisting of four rats. Group I as negative control was given 0.5% CMC solution, group II as positive control was given diclofenac sodium, group III was given sitral, groups IV, V and VI were given 40 mg/200 g BW, 80 mg/200 g BW, and 160 mg/200 g BW essential oil of Ocimum americanum L., emulsified in 0.5% CMC solution. After 30 minutes of test substance administration, left paw of rats injected by 0.2 mL of carrageenan to induce edema. Edema volume was measured using pletismometer every hour for six hours. The result showed that at dose 160 mg/200 g BW gives the best effect in inhibited the inflamation response 44,83%. There was significant difference (pl0.05) at dose 160 mg/200 g BB to negative control. From this study can be concluded that essential oil kemangi leaves has anti-inflammatory activity.

Natural Honey: A New and Potent Anti-Angiogenic Agent in the Air-Pouch Model of Inflammation

Despite reports indicating anti-inflammatory effects of honey, the anti-angiogenic effect of honey and its impact on inflammatory mediators in the air pouch model of inflammation have not yet been studied. The aims of present study were to investigate the effects of honey on angiogenesis, inflammatory cytokine vascular endothelial growth factor (VEGF) level as an important marker of angiogenesis and prostaglandin E2 (PGE2) in the rat air pouch model of inflammation. Male Wistar rats were anesthetized, and then 20 ml and 10 ml of sterile air were injected subcutaneously in the back on days 0 and 3, respectively. On day 6, inflammation was induced by injection of 1 ml of carrageenan 1% into pouches. After 72 h, the rats were sacrificed; pouch fluid was collected in order to determine PGE2 concentration and VEGF level. The Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was assayed using a hemoglobin kit. Honey was able to reduce granulation tissue weight and angiogenesis as well as showing potent inhibitory activities against PGE2 and VEGF in air pouch model of inflammation. The decrease in angiogenesis correlates with the inhibition of PGE2 and VEGF. Honey is potentially useful in the treatment of granulomatous inflammatory conditions. It seems that the anti-angiogenic activities of honey are mediated through modulation of PGE2 and VEGF production.

Anti-inflammatory and toxicity studies of atranorin extracted from Cladina kalbii Ahti in rodents

Atranorin (ATR) is the main compound from the lichen Cladina kalbii Ahti, which grows in the arid regions of northeastern Brazil. This study was conducted to evaluate the anti-inflammatory and toxicological properties of ATR. To evaluate anti-inflammatory properties, paw edema was induced by injecting 0.1 mL of carrageenan into the subplantar region of the right hind paw of rats, and leukocyte migration was induced by injection of 500 µL of carrageenan into the peritoneal cavity of mice. In addition, we determined ATR cytotoxicity in L929 cells by MTT assay and acute (5 g/kg-single dose) and subchronic (50 mg/kg-30 days) toxicity tests in Wistar rats. The results showed that ATR (100 mg/kg and 200 mg/kg) exhibited significant anti-inflammatory activity (paw edema and leukocyte migration). In the acute toxicity test, the animals showed hypoactivity and lethargy during the initial period (first 6 hours) and increase in total protein, total and indirect bilirubin, and alkaline phosphatase after 14 days in ATR-treated male rats. The subchronic toxicity test revealed increases in total protein, globulin, gamma-glutamyl transferase, alkaline phosphatase, and total and direct bilirubin in ATR-treated female rats. Histological analysis revealed no changes in the architecture and morphology of the organs. These results suggest that ATR has significant anti-inflammatory activity, with no significant acute and subchronic toxicity or cytotoxicity.

The effects of 5HT 3 receptor antagonist granisetron on inflammatory parameters and angiogenesis in the air-pouch model of inflammation

Background The antagonists of 5HT 3 receptors have shown impressive efficacy in rheumatoid arthritis, osteoarthritis or fibromyalgia. The mechanistic relationships between 5HT 3 receptors, angiogenesis and sequence of cytokine expression, and leukocyte recruitment during inflammation are not clear. We evaluate the effects of granisetron on inflammatory parameters and angiogenesis in rat air-pouch model. Methods Male Wistar rats were anesthetized, and then 20 ml and 10 ml of sterile air were injected subcutaneously in the back on day 0 and day 3, respectively. On day 6, inflammation was induced by injection of 1 ml of carrageenan 1% into pouches. After 6 and 72 h, the rats were sacrificed; pouch fluid was collected in order to determine exudate volume, the number of accumulated cells and TNFα/PGE 2 concentration. Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was assayed using a hemoglobin kit. Results Leukocyte accumulation was dose-dependently inhibited by granisetron both at 6 and 72 h after induction of inflammation. All doses of granisetron decreased hemoglobin level in the whole granulation tissue in a bell-shaped manner. Vascular network formation was also inhibited by granisetron. Granisetron increased PGE 2 level at a lower dose (50 μg/pouch) but higher doses (100 and 200 μg/pouch) inhibited the release. At the same time, TNFα production was decreased by the lower dose and increased by higher doses of granisetron in a reciprocal fashion. Conclusions Anti-inflammatory activities of 5HT 3 receptor antagonist, granisetron probably are mediated through modulation of TNFα/PGE 2 production and leukocyte infiltration.

THE IMPACT OF GENDER ON THE INFLAMMATORY PARAMETERS AND ANGIOGENESIS IN THE RAT AIR POUCH MODEL OF INFLAMMATION

Objective(s) Air pouch is a well-established inflammatory model in which fluid extravasations; leukocyte migration, angiogenesis and other parameters involved in the inflammatory response can be measured. In this study, the influence of gender on inflammatory parameters has been examined in the air pouch model. Materials and Methods To induce air pouch, adult male and female Wistar rats were anesthetized, then 20 ml and 10 ml of sterile air were injected subcutaneously on the back on day 0 and day 3, respectively. On day 6, inflammation was induced by injection of 1 ml of carrageenan 1% into pouches. After 6 and 72 hr, the rats were sacrificed, pouch fluid was collected in order to determine exudates volume and the accumulated cells were counted using a hemocytometer. Pouches were dissected out and weighed. Angiogenesis of granulomatous tissue was assayed using hemoglobin kit. Results Analysis of our data demonstrated a sexually dimorphic pattern in inflammation parameters both in acute and chronic forms (P<0.05). The value of angiogenesis in the air pouch model in male rat was higher than that female rats (P<0.001). Conclusion The degree of inflammation and angiogenesis induced in Wistar rat air pouch model is gender-dependent, suggesting that gender may be a key consideration in the design of inflammation experiments.

Anti-Inflammatory Effects of an Ethanol Extract of Angelica gigas in a Carrageenan-Air Pouch Inflammation Model

Anti-inflammatory effects of an ethanol extract of Angelica gigas (EAG; 50, 160, or 500 mg/kg) were investigated in a carrageenan-induced air pouch inflammation model. Injection of 1 ml of carrageenan (1%) into mouse air pouches markedly increased the exudate volume and exudate albumin concentration, which were significantly attenuated by oral pretreatment with EAG. EAG also markedly reduced carrageenan-induced infiltrations of neutrophils, monocytes, and lymphocytes, but did not influence eosinophils or basophils. Carrageenan dramatically increased levels of tumor necrosis factor-alpha and interleukin-6, which might be derived from the infiltrated cells. It also elevated nitric oxide, and slightly increased prostaglandin E(2). EAG pretreatment significantly lowered tumor necrosis factor-alpha and nitric oxide, but did not alter interleukin-6 or prostaglandin E(2) levels. These results indicate that EAG attenuates some inflammatory responses by blocking the tumor necrosis factor-alpha-nitric oxide pathway, and that EAG could be a promising anti-inflammatory drug candidate for inflammatory diseases.

Microscopic Findings in a Muscular Pain Induced Murine Model

Background: It has been suggested that muscular pain may induce skeletal muscle damage. But the mechanism of such skeletal muscle damage is not known. This study was performed to investigate the effect of carrageenan induced muscular pain on the tibialis anterior muscle of the rat. Methods: Muscular pain was induced by injecting 0.1 ml of carrageenan into the tibialis anterior muscle of Sprague-Dawley rats. 48 hours after carrageenan injection, animals were killed, and tissues were fixed in 10% neutral buffered formalin (NBF). The tissues were then dehydrated, embedded, sectioned at 5 , stained with phosphotungstic acid hematoxylin (PTAH), and observed under a light microscope. Results: Carrageenan induced muscular pain was associated with a wave-like arrangement of muscle cells, which were separated by intercellular gaps in tibialis anterior muscle. Conclusions: This finding suggests that carrageenan may induce muscular pain damage in the tibialis anterior muscle of rat, as evidenced by a divided wave like muscle cell arrangement.

Effect of Carrageenan-induced Inflammatory Muscle Pain on Gastrocnemius Muscle Tendon in the Rat

Background: It has been suggested that muscle pain may induce skeletal muscle tendon damage, but the mechanism of this process is not known. The purpose of this study was to investigate gastrocnemius muscle tendon damage on Sprague-Dawley rats after inducing inflammatory muscle pain with carrageenan. Methods: Rats were anesthetized with sevoflurane. Muscle pain was induced by injecting 0.1 ml of carrageenan into the gastrocnemius muscle. Rats were killed on 48 hours after carrageenan injection. Muscle tendons were fixed in 10% neural buffered formalin (NBF), dehydrated, embedded, and sectioned at 4 Sections were then stained with phosphotungstic acid hematoxylin(PTAH), mounted, and observed under a light microscope. Results: Carrageenan-induced inflammatory muscle pain was associated with reduced tendon fiber and fibroblast numbers. Conclusions: This finding suggests that carrageenan-induced inflammatory muscle pain damages the gastrocnemius muscle tendon in the rat by reducing tendon fiber and fibroblast numbers.

Effect of Cleome arabica Leaf Extract on Rat Paw Edema and Human Neutrophil Migration

The anti-inflammatory activity of Cleome arabica leaf extract was studied in vivo and in vitro. Firstly, the extract was examined for its anti-inflammatory activity using carrageenan-induced rat paw edema as a model of acute inflammation. A subplantar injection of 0.1 ml of carrageenan 1% induced a progressive swelling of the rat paw in all time points, that reached a maximal volume in placebo group within 5 h. Results showed that pre-treatment of rats by Cleome arabica leaf extract, 1 h prior the injection of the phlogogenic agent, prevented the increase of the edema in dose-dependent manner with an ED 50 of 231 mg/kg, body weight. The extract doses 100, 200 and 300 mg/kg, reduced edema to 65.54 ± 5.2%, 57.86 ± 8%, and 41.54 ± 3.6%, respectively, 5 h after the carrageenan injection. Secondly, we have examined the effect of Cleome arabica leaf extract on human neutrophil migration induced by fMLP (10 -7 M), using 48-well chemotaxis chamber. Results showed that the extract inhibited neutrophil chemotaxis significantly (p < 0.01) and in a dose-dependent manner. Neutrophil migration was reduced to 16.71 ± 4.6% in presence of 50µg/ml of Cleome arabica leaf extract. It appears that the antiinflammatory activity of Cleome arabica leaf extract, observed in vivo as well as in vitro, could be due to its high flavonoid content (19%). These results may contribute to explain the use of this plant in folk medicine.

Cimetidine inhibits nitric oxide associated nitrate production in a soft-tissue inflammation model in the horse.

Cimetidine (CIM) is an H2-receptor antagonist that has been used in racehorses in an attempt to reduce the occurrence of stress-related gastric ulceration. It has also been shown to produce several useful effects other than its gastric acid suppression properties. Further, it is a well documented antagonist of cytochrome P-450 (CYP) mediated oxygenation reactions. Nitric oxide (NO), a recently discovered mediator or modifier of numerous physiological functions, is generated by several forms of nitric oxide synthase (NOS), one of which is inducible (iNOS). Inducible NOS, expressed in neutrophils and macrophages as part of the inflammatory response to noxious stimuli, contains both a CYP and a CYP reductase domain. Because of the similarity of structure of iNOS and CYP, it was decided to determine whether CIM could reduce NO production, using a carrageenan inflammation model in the horse. Two experiments were conducted. In Trial 1, six female Thoroughbred horses each had three tissue chambers inserted subcutaneously on the sides of the neck. The study was divided into three treatments: 0.9% NaCl (NaCI), CIM (3 mg/kg), and aminoguanidine (AG; 25 mg/kg), an inhibitor of iNOS. Each mare received three i.v. injections 12 h apart prior to instillation of 1 mL of carrageenan into the test chamber. Blood and tissue chamber fluid (TCF) were collected serially. Concentrations of NO3- (the major metabolite of NO), albumin, total protein, CIM and AG were measured and complete cell counts and differentials were conducted. Trial 2 also used six female Thoroughbred horses implanted with at least two tissue chambers inserted subcutaneously on the sides of the neck. The study was divided into two treatments: NaCl (0.9%) and CIM (6 mg/kg). Each mare received seven i.v. injections of either NaCl or CIM 8 h apart prior to instillation of 1 mL of carrageenan into the test chamber. Blood and TCF were collected serially as before, and analysed for NO3- and CIM content. Areas under the curve (AUC) of the different parameters were calculated for the periods of -1-1, -1-3 and -1-7 days (Trial 1) and -2-1 for Trial 2. Absolute values were also compared at 4, 8 and 12 h postcarrageenan. Saline treatment did not reduce the elevated concentrations of NO3- in either plasma or TCF. Plasma, test chamber and control chamber NO3-concentrations rose from 0 to 12 h, and were very similar in all three sampled fluids. Cimetidine significantly (P< or =0.05) decreased NO3- production in plasma over the periods of -1-1, -1-3, and -1-7 days post inflammation when compared to NaCl treatment in Trial 1. Aminoguanidine and CIM decreased NO3-production in TCF for the periods -1-1, 1-3, and -1-7 days post inflammation in Trial 1 and -2-1 for Trial 2. Both CIM and AG also significantly reduced NO3-concentrations in plasma and TCF at 12 h postinitiation (Trials 1 and 2). Thus CIM, at the doses studied, was capable of reducing NO3- concentrations in this model as effectively as AG, a relatively specific inhibitor of iNOS activity.

Anti-inflammatory properties of IL-1 in carrageenan-induced paw oedema

To evaluate any inhibitory effect of a single dose of human recombinant interleukin-1 beta (hrIL-1 beta) on the severity of carrageenan-induced oedema in rats (a commonly used model of acute inflammation), we first injected 0.1 ml of carrageenan (0.2%, 0.5%, or 2%) to induce mild, moderate, or severe inflammation, respectively into the right rear footpad. Then we promptly injected the interleukin (0.02, 0.2, or 2 micrograms) subcutaneously into the flank. The initial rapid increase in volume of the injected paw (within 2 h of the subplantar injection) was independent of the dose of carrageenan, whereas the increase in volume by 6 to 10 h was dose-dependent. All doses of HrIL-1 beta inhibited the carrageenan-induced swelling at the 6th hour. In the moderate and severe carrageenan-induced oedemas, the higher dose of HrIL-1 beta induced a delayed inflammation peaking at 10 h instead at 6 h.