Carrageenan-induced Acute Inflammation In Rats Research Articles

Acute anti-inflammatory effect of methanolic extracts of leaf, bark and fruit of Averrhoa bilimbi on carrageenan-induced acute inflammation in rats

Acute anti-inflammatory effect of methanolic extracts of leaf, bark and fruit of Averrhoa bilimbi on carrageenan-induced acute inflammation in rats

Effect of Panzeria Alaschanica Kupr. on Carrageenan-Induced Acute Inflammation in Rats

Objectives: In the present study, we aimed to investigate the effect of Panzeria alaschanica Kupr. (P. alaschanica) on carrageenan-induced acute inflammation in rats. Method: Carrageenan-induced rat paw edema was used to evaluate the anti-inflammatory activity. P. alaschanica extract (32, 64, and 160 mg/kg/ BW) or vehicle was given orally 60 minutes before the subplantar injection of carrageenan. Ibuprofen (100 mg/kg) was used as a standard drug. The carrageenan-injected paw was measured 30, 60, 120, 180, and 240 minutes after the carrageenan injection. The levels of serum tumor necrosis factor (TNF)-α, interleukin (IL)-ELISA measured 1β, and IL-6. Results: The P. alaschanica at all given doses significantly (p˂0.01) inhibited carrageenan-induced rat paw edema. Moreover, it significantly reduced TNF-α, IL-1β, and IL-6 serum levels at different doses (p˂0.01). The anti-inflammatory effect of P. alaschanica was comparable to ibuprofen. Conclusion: P. alaschanica has an anti-inflammatory impact on carrageenan-induced paw edema in rats. The mechanism of action may partly be via reducing the levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6.

EVALUATION OF ANTI-INFLAMMATORY PROPERTIES OF ETHANOLIC LEAF, FLOWER AND SEED EXTRACTS OF LAGERSTROEMIA SPECIOSA (L.) PERS (LYTHRACEAE) AGAINST CARRAGEENAN-INDUCED ACUTE INFLAMMATION IN ALBINO RATS

Lagerstroemia speciosa medicinal properties suggest that it may have anti-inflammatory effects on acute inflammation. The present study was performed to investigate the anti-inflammatory effect of L. speciosa ethanolic leaf, flower, and seed extract (LELE, LEFE, and LESE) on carrageenan-induced acute inflammation in rats. This plant is commonly called Pride of India refers to the various parts of this plant, including the leaves, flowers, and seeds, which are used as folk medicine. It has been demonstrated that the phytochemical and anti-inflammatory activities are effective in the treatment of inflammatory conditions in traditional medicine. The qualitative phytochemical investigation of L. speciosa leaf, flower, and seed revealed that it contained steroids, terpenoids, glycosides, polyphenolic compounds, amino acids, saponins, alkaloids, flavonoids, reducing sugars, tannins, and many other active metabolites. Studies have shown active antiinflammatory ingredients in L. speciosa ethanolic extracts of leaf (LELE), flower (LEFE), and seed (LESE). The ethanolic extracts of L. speciosa (LELE, LEFE and LESE) were investigated for anti-inflammatory activity in carrageenan-induced paw edema in albino rats and compared to control and standard drug, Diclofenac injection. The experimental plant extracts were given orally at a concentration of 250 and 500 mg/kg b.w. before carrageenan injection. In the paw edema evaluation, the paw volume was measured in the early (from 0 min-3 h) and late (4-6 h) phases of edema formation. In acute inflammation paw models, the ethanol extracts significantly reduced paw edema. The result obtained is indicative that the ethanolic extract of leaf and seed with high dose of 500 mg/kg b.w. produced 42% of inhibition and is low as compared to the standard drug. Low dose of ethanolic flower extract of L. speciosa inhibitory is equal to the low dose of seed extract; it is 1% lower than the standard and 2% lower than the control.

Anti-inflammatory activity of Atavijambira (Atalantia monophylla DC.) root and stem

Abstract Background: Atalantia monophylla DC. family Rutaceae, a promising drug, has multifaceted ethnomedicinal claims to treat rheumatism, arthritis, paralysis, cough, skin diseases, etc., In traditional practice, root and stem are administered to treat rheumatism and arthritis, respectively. Aim: The aim of this study was to evaluate the anti-inflammatory activity of the root and stem of A. monophylla against carrageenan-induced acute paw edema in wistar albino rats. Materials and methods: Shade dried root and stem were grinded separately into a fine powder (120#) by the mechanical grinder. Test drugs were prepared in Phanta (hot infusion) form and used as fresh (A. monophylla root Phanta [AMRP] and A. monophylla stem Phanta [AMSP]). Difference between the groups was statistically determined by one-way ANOVA, followed by Dunnett’s multiple “t” test for unpaired data. Results: AMSP showed a significant decrease in paw inflammation at all-time interval (P < 0.05), whereas AMRP produced nonsignificant decrease in paw inflammation at 1 h (43.53%) and 5 h (25.74%) while significant (P < 0.05) anti-inflammatory activity at 3 h (36.35%) in comparison with the normal control group. Conclusion: The present study concluded that A. monophylla stem is having significant anti-inflammatory activity in comparison to its root when administered in Phanta form against carrageenan-induced acute inflammation in rats.

Effect of Aronia melanocarpa fruit juice on carrageenan-induced paw edema in metabolic syndrome rats

INTRODUCTION: Chronic, low-grade inflammation plays a critical role in the pathogenesis of the metabolic syndrome (MS). Aronia melanocarpa fruits are rich in biologically active compounds—polyphenols, which possess a variety of health benefits including an anti-inflammatory effect. AIM: The aim of this article is to evaluate the effect of polyphenol-rich Aronia melanocarpa fruit juice (AMFJ) on carrageenan-induced acute inflammation in rats with diet-induced MS. MATERIALS AND METHODS: Forty male Wistar rats were included in the experiment. They were allocated into 4 groups: MS, MS+AMFJ 2.5 , MS+AMFJ 5 , and MS+AMFJ 10, all receiving high-fat high-fructose diet and 10% fructose in the drinking water for 10 weeks. The MS group served as a control and was treated daily with distilled water orally, while the other groups received AMFJ at doses of 2.5 mL/kg, 5 mL/kg, and 10 mL/kg, respectively. At the end of the experiment, carrageenan was injected in the left hind paw in order to induce acute inflammation. Paw edema was evaluated with plethysmometer on the 30 th min and 1 st , 2 nd , 3 rd , 4 th , and 5 th hour after the injection. RESULTS: In the MS group, the carrageenan-induced paw edema increased gradually with time reaching the highest value on the 5 th hour. A decrease throughout the whole 5-hour period was observed in groups treated with AMFJ, the effect being most pronounced and statistically significant in MS+AMFJ 5 group on the 2 nd and 3 rd hour. CONCLUSION: Aronia melanocarpa fruit juice treatment in rats with MS resulted in a decrease in the carrageenan-induced paw inflammation. The anti-inflammatory effect might be attributed to the polyphenols in AMFJ.

Pregabalin Attenuates Carrageenan-Induced Acute Inflammation in Rats by Inhibiting Proinflammatory Cytokine Levels.

Pregabalin (PGB) is a compound used in the treatment of epilepsy, anxiety, and neuropathic pain. Experimental data also indicate that PGB can reduce inflammatory pain. We aimed to investigate the anti-inflammatory effects of PGB on carrageenan (CAR)-induced paw edema and its effects on tumor necrosis factor-α (TNF-α) and interleukine-1β (IL-1β) acting as acute phase cytokines in inflammation, and anti-inflammatory cytokine IL-10, in rats. Single doses of PGB 30, 50, and 100 mg/kg and indomethacin (INDO) 5 mg/kg in the treatment groups and saline in the control group were injected once intraperitoneally prior to administration of 100 μl of 1% CAR into the right hind paw of the rats. The paw thickness was measured using gauge calipers (Vernier calipers) before (0 hour) and every hour afterwards for 6 hours following the inflammation induction. The cytokine levels in the blood serum obtained intracardiacally were determined after 6 hours using the enzyme-linked immunosorbent assay method. p<0.05 was considered statistically significant. There was no significant difference between the 0 and 6th hour considering the paw thickness in all groups, except in the CAR group. CAR significantly increased the paw thickness at 6 hours compared to the 0 hour. All doses of PGB and INDO significantly reduced the paw thickness after 6 hours compared to the CAR group. The TNF-α and IL-1β levels in the PGB and INDO groups were comparable to the control group, whereas in the CAR group, these levels were increased. The IL-10 level was enhanced in the PGB 50 mg/kg and INDO groups. It was observed that all doses of PGB exerted anti-inflammatory-like effects comparable to INDO, supported by their effects on the levels of cytokines.

Pro-Inflammatory Cytokines Expression of Carrageenan-Induced Acute Inflammation in Rats Pre-Administered with Freeze-Dried Carica papaya Leaf Juice and Citropten

Pro-Inflammatory Cytokines Expression of Carrageenan-Induced Acute Inflammation in Rats Pre-Administered with Freeze-Dried Carica papaya Leaf Juice and Citropten

Modulation of reactive oxygen species production, apoptosis and cell cycle in pleural exudate cells of carrageenan-induced acute inflammation in rats by rutin.

The present study seeks to investigate the effect of rutin, a flavonoid compound in rat models of acute inflammation induced by carrageenan (CAR). Twenty-four female Wistar rats weighing 222-247 g received saline or 2% λ-carrageenan in the pleural cavity and treatment with rutin (80 mg kg-1) or saline by oral gavage for 21 days prior to the intrapleural induction of CAR. After 4 h of induction, the rats were euthanized, the plasma was prepared from the blood for the analysis of haematological parameters and the pleural exudate was obtained for the analysis of the total cell count, cell viability, reactive oxygen species (ROS) production, apoptosis and cell cycle. The result revealed that rutin exhibited anti-inflammatory effects by modulating the ROS level, apoptosis and cell cycle. This study indicates that rutin may exert a protective effect against ROS-mediated oxidative damage associated with an anti-inflammatory activity in rat models of acute inflammation.

Extraction, characterization and evaluation of Kaempferia galanga L. (Zingiberaceae) rhizome extracts against acute and chronic inflammation in rats

Ethnopharmacological relevanceThe rhizomes of an acaulescent perennial herb, Kaempferia galanga Linn (Family: Zingiberaceae), used as traditional ayurvedic herb to get relief from indigestion, swelling, pain, high blood pressure and dyslipidemia. Aim of the studyTo prepare and characterize various extracts of Kaempferia galanga (K. galanga) for their comparative evaluation for the identification of the most efficacious extract and its possible pharmacological implication in acute and chronic inflammatory paradigm. Materials and methodsDried and powdered rhizome of K. galanga was subjected to alcoholic extraction as well as successive extractions with various solvents. After phytochemical characterization, all the extracts were standardized for the presence of ethyl-p-methoxycinnamate. The extracts, and the isolated compound, were tested against carrageenan-induced acute inflammation in rats. The most promising extract was tested against adjuvant-induced chronic inflammation in rats. Further, local myeloperoxidase (MPO) levels were investigated to establish the possible mechanism of action. ResultsAmong the extracts, petroleum ether extract (SKG-1) and crude alcoholic extract (KG) had the maximum quantity of ethyl-p-methoxycinnamate. SKG-1 (300mg/kg) was found effective against acute inflammation in rats. Further, SKG-1 (100mg/kg) reversed the inflammation and elevated MPO levels found in the chronic model. ConclusionsThe results suggest that among all the extracts of K. galanga, SKG-1 effectively suppresses the progression of acute and chronic inflammation in rats by inhibition of neutrophil infiltration.

Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors

This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3–10mg/kg) and PGL (1–20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated.Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1–10mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized.These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes.

Evaluation of antioxidative, analgesic and anti-inflammatory activities of methanolic extract of Myrica nagi leaves - an animal model approach

Myrica nagi (family Myricaceae) is commonly known as Kathphal (Hindi) and Bayberry (English) and it has a long history of usage in traditional medicine. It is popular actinorhizal plant for its symbiotic relationship with Frankia. This study was taken in force to estimate the analgesic, anti-inflammatory and anti-oxidative activities of methanolic extract of Myrica nagi (MMN) in an animal model. Anti-oxidative property of MMN was assessed by free radical scavenging assay (DPPH method). The acute toxicity test of methanolic extract of MMN revealed that the median lethal dose (LD50) was found to be 2080 mg/kg body weight in mice. The anti-inflammatory property was evaluated by carrageenan-induced acute inflammation in rats by measuring rat paw volume at different time intervals and toxicological analysis using mice. The analgesic effect was measured in Wistar rats using the acetic acid-induced writhing test and MMN at 200 mg/kg BW showed 54.56 % inhibition of writhing. MMN showed higher anti-oxidant activity in DPPH assays as compared to standard. High dose of MMN showed a significant reduction (21.71 %) in inflammation after 4 h of treatment, which was comparable to diclofenac (10 mg/kg BW; 32.75 %)-treated group. Significant reduction (p < 0.05) in the levels of inflammatory cytokine (IL-1β and TNF-α) markers were also observed in serum of MMN-treated animals as compared to control. Taken together, the phenolic compounds of MMN may serve as potential herbal drug for amelioration of acute inflammation due to their modulatory action on free radicals.

Toxicological Evaluation of Emblica officinalis Fruit Extract and its Anti-inflammatory and Free Radical Scavenging Properties.

Background:Emblica officinalis (Euphorbiaceae), popularly known as Indian gooseberry or “Amla” in India, is used in Ayurveda as “rejuvenating herb” since ancient times.Objective:This study was carried out to estimate toxicity, anti-inflammatory, and antioxidative activities of the methanolic extract of Emblica officinalis fruit (MEO) in an animal model.Materials and Methods:Antioxidative property of MEO was assessed by in vitro assays such as phosphomolybdenum assay (total antioxidant capacity), free radical scavenging assays 1,1-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis and 3-ethylbenzthiazoline-6-sulphonic acid (DPPH and ABTS method) and lipid peroxidation assay (LPO). The anti-inflammatory property was evaluated by carrageenan-induced acute inflammation in rats by measuring rat paw volume at different time intervals and toxicological analysis using mice.Results and Discussion:High performance liquid chromatography studies revealed the presence of gallic acid (2.10%), mucic acid (4.90%), ellagic acid (2.10%), quercetin (28.00%), rutin (3.89%), and β-glucogallin (1.46%). MEO showed highest antioxidant activities by using DPPH (17.33–89.00%), ABTS (23.03–94.16%), nitric oxide scavenging activity (12.94–70.16%), LPO (56.54%), and phosphomolybdenum assay (142 ± 6.09 μg/ml). The LD50 was found to be approximately 1125 mg/kg (p.o). High dose of MEO showed significant reduction (72.71%) in the inflammation after 4 h of treatment, which was comparable to diclofenac (10 mg/kg) (61.57%) treated group. Significant reduction (P < 0.05) in the inflammatory cytokine (interleukin-1β and tumor necrosis factor-α) markers were also observed (57.25% and 35.41%, respectively) in serum of MEO treated animals as compared to control.Conclusion:Taken together, phenolic compounds of MEO may serve as a potential herbal drug for amelioration of acute inflammation due to their modulatory action on free radicals.SUMMARY The methanolic extract of Emblica officinalis fruit (MEO) has potent antioxidant activity as assessed by DPPH, ABTS and LPO assaysMEO has potent anti-inflammatory activity in carrageenan induced paw edema modelThe phenolic compounds of MEO might be a potential herbal drug for amelioration of acute inflammation. Abbreviations used: ROS, reactive oxygen species; RNS, reactive nitrogen species, LPO, lipid peroxidation, NO, nitric oxide, IL, interleukin; TNF α tumor necrosis factor alpha; NSAIDs, nonsteroidal anti inflammatory drugs; AA, ascorbic acid; MEO, methanolic extract of Emblica officinalis fruit; ABTS+; 2,2’ azino bis 3 ethylbenzthiazoline 6 sulphonic acid; DPPH, 1,1 diphenyl 2 picrylhydrazyl; HPLC, high performance liquid chromatography; MDA, malondialdehyde; DMSO, dimethyl sulphoxide; ELISA, enzyme linked immunosorbent assay.

Remedial effects of novel 2,3-disubstituted thiazolidin-4-ones in chemical mediated inflammation

Three thiazolidin-4-one derivatives were synthesized, purified and characterized by chromatographic and spectroscopic methods. In the in vitro assays, these compounds inhibited reactive oxygen species (ROS), nitrite and cytokine generation in RAW 264.7 murine macrophages and whole blood. These derivatives attenuated carrageenan-induced acute inflammation in rats. The most effective compound 4C possessed identical anti-inflammatory action at two doses (50 and 100mg/kg). Further, the effect of compound 4C on locally induced inflammatory mediators was investigated in carrageenan-induced air pouch inflammation in rats. In this model, compound 4C inhibited the cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6 (systemic and local). Additionally, compound 4C was able to reduce locally elevated prostaglandin-E2 (PGE2). Inhibition of leukocyte infiltration by compound 4C was correlated with reduced locally released myeloperoxidase (MPO). To conclude, compound 4C corrected the inflammatory condition by negative effect on cytokine (TNF-α, IL-6) network and prostaglandin-E2 generation.

Cat’s whiskers flavonoid attenuated oxidative DNA damage and acute inflammation: its importance in lymphocytes of patients with rheumatoid arthritis

Cleome gynandra L. (Capparidaceae) is one of the vegetables commonly known as 'Hurhur' and 'Karaila' in India, 'Pe Hua Tsai' in China and "Cat's whiskers" in English. Present study was aimed to characterize previously isolated Cat's whiskers flavonoid as 5-hydroxy-3, 7, 4' -trimethoxyflavone (5HTMF) and to evaluate its effect on carrageenan-induced acute inflammation in rats and hydrogen peroxide induced DNA damage in mouse macrophages. The ex vivo effect of 5HTMF upon generation of free radicals in the mononuclear lymphocytes of patients with rheumatoid arthritis (RA) was also evaluated. 5HTMF not only reduce the swelling of hind paw in rats from 1 to 3h of carrageenan injection but also decreased serum nitric oxide (NO) production. Toxic hydrogen peroxide induced oxidative DNA damage that was significantly decreased by 5HTMF. Though oxidative stress is a potential biomarker for determining disease activity in patients with RA, surprisingly 5HTMF inhibited the superoxide, hydroxyl and NO radicals in the isolated peripheral blood mononuclear lymphocytes of patients with RA. From the above study, it may be concluded 5HTMF attenuated acute inflammation by inhibiting NO and by protecting the oxidative DNA damage due to hydrogen peroxide scavenging property. It was also equally effective in scavenging the free radicals in lymphocytes of patients with RA. Collectively, our results indicate that 5HTMF as well as leafy vegetable of Cat's whiskers may be a promising nontoxic food alternative in attenuating the oxidative stress, meriting further studies on other human inflammatory cells.

Anti-inflammatory potential of curcumin and quercetin in rats

Flavonoids are group of compounds that have been shown to possess potent anti-inflammatory effects in both cellular and animal models of inflammation. In the current study, the single and combined effects of the two flavonoids, curcumin and quercetin, against carrageenan-induced acute inflammation in rats were evaluated with emphasis on the role of oxidative stress, anti-inflammatory enzyme, heme oxygenase-1 (HO-1) and proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α). Curcumin (50 mg/kg), quercetin (50 mg/kg) and a combination of both were orally administered for 14 days before carrageenan injection in rats and compared with the reference nonsteroidal anti-inflammatory drug, indomethacin (10 mg/kg). The percentage increase in paw thickness was calculated. Frozen hind paws were used for the estimation of lipid peroxides (malondialdehyde, MDA), nitric oxide (NO), reduced glutathione (GSH), TNF-α level and HO-1 messenger RNA (mRNA) expression. Formalin-fixed hind paws were used for histopathological examination. Results showed that both curcumin and quercetin caused reduction in carrageenin-induced edema and lymphocytes infiltration along with the decrease is being even higher in case of their combination. Additionally, both flavonoids reduced MDA and NO formation, and restored GSH contents in the paw. Furthermore, both flavonoids increased HO-1 mRNA expression and decreased the elevated TNF-α level. Results showed that both flavonoids moderately lowered inflammation, while their combination was more effective. Accordingly, this study suggests that the reduction in oxidative stress and modulation of HO-1 mRNA expression and TNF-α release by curcumin and quercetin may contribute to the synergistic anti-inflammatory effects of these two flavonoids upon combination.

Anti‐Arthritic Activity of Bartogenic Acid Isolated from Fruits of Barringtonia racemosa Roxb. (Lecythidaceae)

The fruits of Barringtonia racemosa are prescribed in the ayurvedic literature for the treatment of pain, inflammation and rheumatic conditions. In present investigation, activity guided isolation of bartogenic acid (BA) and its evaluation in the Complete Freund's Adjuvant (CFA)-induced arthritis in rats is reported. Among the various extracts and fractions investigated preliminarily for carrageenan-induced acute inflammation in rats, the ethyl acetate fraction displayed potent anti-inflammatory activity. Large-scale isolation and characterization using chromatography and spectral study confirmed that the constituent responsible for the observed pharmacological effects was BA. Subsequently the BA was evaluated for effectiveness against CFA-induced arthritis in rats. The results indicate that at doses of 2, 5, and 10 mg kg−1 day−1, p.o., BA protects rats against the primary and secondary arthritic lesions, body weight changes and haematological perturbations induced by CFA. The serum markers of inflammation and arthritis, such as C-reactive protein and rheumatoid factor, were also reduced in the BA-treated arthritic rats. The overall severity of arthritis as determined by radiological analysis and pain scores indicated that BA exerts a potent protective effect against adjuvant-induced arthritis in rats. In conclusion, the present study validates the ethnomedicinal use of fruits of B. racemosa in the treatment of pain and inflammatory conditions. It further establishes the potent anti-arthritic effects of BA. However, additional clinical investigations are needed to prove the efficacy of BA in the treatment of various immuno-inflammatory disorders.

Thioctic acid protects against carrageenan‐induced acute inflammation in rats by reduction in oxidative stress, downregulation of COX‐2 mRNA and enhancement of IL‐10 mRNA

Free radicals are highly reactive species which played an important role in the pathogenesis of acute inflammation. In this study, the protective role of the known antioxidant, thioctic acid, in carrageenan-induced acute inflammation in rats was assessed and was compared to the reference non-steroidal anti-inflammatory drug (NSAID) indomethacin. In addition, the roles of oxidative stress, nitric oxide (NO), inducible cyclooxygenase isoform (COX-2) and interleukin (IL)-10 mRNA expressions in thioctic acid-induced effects were also investigated. Inflammation was induced by injection of 0.1 ml of 1.5% carrageenan into the plantar side of right hind paws of the rats. Thioctic acid (50, 100 or 200 mg/kg), indomethacin (10 mg/kg), DMSO and saline were injected i.p. 2 h before carrageenan injection. The percentage increase in paw weight was calculated. Frozen hind paw were used for estimation of lipid peroxides (MDA), NO, GSH, COX-2 and IL-10 mRNA expression. Formalin fixed hind paw were used for histopathological examination. Thioctic acid (200 mg/kg) reduced both paw edema formation and lymphocytes infiltration more significant than indomethacin itself: Both thioctic acid and indomethacin reduced paw MDA and NO formation. In addition, both agents restored the depleted GSH contents in the paw. Thioctic acid decreased the elevated COX-2 mRNA while indomethacin, failed. Furthermore, thioctic acid increased IL-10 mRNA expression while indomethacin decreased its expression. Thioctic acid exhibited a potent anti-inflammatory effect on carrageenan-induced inflammation compared to the NSAID indomethacin. The mechanisms of thioctic induced protection were proved to be due to reduction of NO, MDA, COX-2 mRNA and induction of GSH, IL-10 mRNA.

Synergistic anti-inflammatory interaction between meloxicam and aminoguanidine hydrochloride in carrageenan-induced acute inflammation in rats

Interaction studies with inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) inhibitor have been conducted to assess the nature of interaction and the possible therapeutic advantage. The interaction between meloxicam – a selective COX-2 inhibitor – and aminoguanidine hydrochloride – a selective iNOS inhibitor – was examined in carrageenan-induced paw edema in rats. Appropriate statistical method was applied to detect the nature of anti-inflammatory interaction. Different doses of meloxicam (1, 3, 10 and 30 mg/kg) or aminoguanidine hydrochloride (10, 30, 100 and 300 mg/kg) were administered orally to adult male albino rats. Higher doses of meloxicam (3, 10 and 30 mg/kg) showed statistically significant anti-inflammatory effect. However, aminoguanidine hydrochloride did not show any anti-inflammatory activity. Combination of sub-threshold dose of meloxicam (1 mg/kg) with increasing doses of aminoguanidine hydrochloride (30, 100 and 300 mg/kg) resulted in synergistic anti-inflammatory effect. Combined therapy with sub-threshold dose of aminoguanidine hydrochloride (30 mg/kg) with increasing doses of meloxicam (1, 3, 10 and 30 mg/kg) also resulted in synergistic anti-inflammatory effect. The possible mechanism of interaction could be the stimulation of COX-2 activity by nitric oxide (NO) by combining with heme component. These results suggest that co-administration of meloxicam and aminoguanidine hydrochloride may be an alternative in clinical control of inflammation.

Effect of Methylguanidine in a Model of Septic Shock Induced by LPS

Septic shock, a severe form of sepsis, is characterized by cardiovascular collapse following microbial invasion of the body. The progressive hypotension, hyporeactivity to vasopressor agents and vascular leak leads to circulatory failure with multiple organ dysfunction and death. Many inflammatory mediators (e.g. TNF-α, IL-1 and IL-6) are involved in the pathogenesis of shock and, among them, nitric oxide (NO). The overproduction of NO during septic shock has been demonstrated to contribute to circulatory failure, myocardial dysfunction, organ injury and multiple organ failure. We have previously demonstrated with in vitro and in vivo studies that methylguanidine (MG), a guanidine compound deriving from protein catabolism, significantly inhibits iNOS activity, TNF-α release and carrageenan-induced acute inflammation in rats. The aim of the present study was to evaluate the possible anti-inflammatory activity of MG in a model of septic shock induced by lipopolysaccharide (LPS) in mice. MG was administered intraperitoneally (i.p.) at the dose of 30 mg/kg 1 h before and at 1 and 6 h after LPS-induced shock. LPS injection (10 mg/kg in 0.9% NaCl; 0.1 ml/mouse; i.p.) in mouse developed a shock syndrome with enhanced NO release and liver, kidney and pancreatic damage 18 h later. NOx levels, evaluated as nitrite/nitrate serum levels, was significantly reduced in MG-treated rats (78.6%, [Formula: See Text]). Immunohistochemistry revealed, in the lung tissue of LPS-treated group, a positive staining for nitrotyrosine and poly(adenosine diphosphate [ADP] ribose) synthase, both of which were reduced in MG-treated mice. Furthermore, enzymatic evaluation revealed a significant reduction in liver, renal and pancreatic tissue damage and MG treatment also improved significantly the survival rate. This study provides evidence that MG attenuates the degree of inflammation and tissue damage associated with endotoxic shock in mice. The mechanisms of the anti-inflammatory effect of MG is, at least in part, dependent on the inhibition of NO formation.

Potentiation of diclofenac-induced anti-inflammatory response by aminoguanidine in carrageenan-induced acute inflammation in rats: the role of nitric oxide.

To investigate whether aminoguanidine (AG) treatment enhances the anti-inflammatory effect of diclofenac in an acute inflammation model in rats. In 48 rats carrageenan-induced paw edema was used as an acute inflammation model. Inflammatory activity was assessed at 1.5, 3 and 6 h after sub-planter injection of carrageenan (0.1 ml of a 1% solution in 0.85% saline). The anti-inflammatory effect of diclofenac (25 mg/kg, i.p.) was studied in comparison to that of the selective inducible nitric oxide synthase (iNOS) inhibitor, AG, and of nitric oxide donor, sodium nitroprusside (SNP). AG, failed to inhibit inflammation during the first 3 h following carrageenan administration, but caused a slight, although statistically insignificant inhibition at 6 h. Diclofenac significantly reduced the carrageenan-induced edema in rat paw at all the time points studied. Administration of diclofenac after AG pretreatment caused significant (P < 0.001) reduction in edema that was double that of diclofenac alone 6 h after carrageenan injection. Administration of SNP as a single dose after AG pretreatment prevented any potentiation of anti-inflammatory response that was observed in the case of AG combined with diclofenac treatment. These results show that AG markedly potentiates the anti-inflammatory activity of diclofenac at 6 h and this potentiation effect is nitric oxide-dependent.