Carrageenan-induced Inflammatory Paw Edema Research Articles

Serjania marginata Casar. Hydroalcoholic Extract Reduced Cytokine and Inflammatory Parameters in Experimental Models of Inflammation and Infection in Mice

Pharmacognosy Research,2022,14,2,127-134.DOI:10.5530/pres.14.2.18Published:April 2022Type:Original ArticleAuthors:Maicon Matos Leitão, Joyce Alencar Santos Radai, Luis Fernando Benitez Macorini, Thiago Leite Fraga, Silvia Cristina Heredia-Viira, Claudia Andrea Lima Cardoso, Arielle Cristina Arena, and Candida Aparecida Leite Kassuya Author(s) affiliations:Maicon Matos Leitão1,2,*, Joyce Alencar Santos Radai1, Luis Fernando Benitez Macorini1, Thiago Leite Fraga1, Silvia Cristina Heredia-Vieira3, Claudia Andrea Lima Cardoso4, Arielle Cristina Arena5, Candida Aparecida Leite Kassuya1 1School of Health Sciences, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul State, BRAZIL. 2School of Health Sciences, Unigran Capital University Center, Campo Grande, Mato Grosso do Sul State, BRAZIL. 3Center of Health Sciences, Anhanguera- Uniderp University, Campo Grande, Mato Grosso do Sul State, BRAZIL. 4Center of Studies on Natural Resources, Mato Grosso do Sul State University, Dourados, Mato Grosso do Sul State, BRAZIL. 5Department of Morphology, Institute of Biosciences of Botucatu, Paulista State University, Botucatu, SP, BRAZIL. Abstract:Objectives: This study investigated the antimycobacterial, anti-inflammatory and antihyperalgesic effects of hydroalcoholic extract from leaves of S. marginata (EESM) in in vitro and in vivo models. Methods and Results: EESM (0.98–1000 μg/ml) was evaluated in in vitro against Mycobacterium tuberculosis, M. bovis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus epidermidis. The EESM oral administration (p.o.) (30, 100 and 300 mg/kg) and dexamethasone subcutaneous injection (s.c.) (1 mg/kg) were tested against the carrageenan-induced inflammatory paw edema and pleurisy in Swiss mice. The EESM (30 and 100 mg/kg, p.o.) and dexamethasone (1 mg/kg, s.c.) were tested against the CFA-induced paw inflammation and M. bovis (bacillus Calmette-Guerin - BCG)-induced pleurisy in C57bL6 mice. The minimum inhibitory concentration (MIC) of EESM in the presence of M. tuberculosis was 62.4 μg/ml. The values of MIC of EESM in the presence S. epidermidis, K. pneumoniae were 1000 μg/mL while EESM did not interfere against P. aeruginosa growth. EESM significantly inhibited paw edema/mechanical hyperalgesia in carrageenan induced paw inflammation and leukocytes migration/proteins exudation in carrageenan-induced pleurisy model. In the BCGinduced pleurisy model, the daily treatment for 7 days, with EESM inhibited the levels of IL-1β in blood and in pleural exudate. The EESM did not alter the mycobacterial growth in the cell culture from pleural lavage, spleen and liver samples collected from BCG-treated animals. The EESM significantly inhibited the persistent edema and mechanical hyperalgesia induced by CFA. Conclusion: This study confirms the EESM anti-inflammatory property and showed that EESM has high potency in inducing inhibition of mycobaterial growth and low potency or no effects in relation to other microorganisms. Key words: Mycobacterium tuberculosis, Bacillus Calmette-Guerin (BCG), Cipó-timbó, Inflammation, Tuberculosis. View:PDF (455.97 KB)

Beneficial interaction of pycnogenol with indomethacin in rats.

Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.

Mucus from different fish species alleviates carrageenan-induced inflammatory paw edema in rats

Objective: To determine the anti-inflammatory effects of mucus obtained from different fish species on the carrageenan-induced acute paw edema in rats. Methods: Forty-two rats were randomly divided into seven groups. Acute paw edema was induced by 0.1 mL of 1% carrageenan, and a single dose of diclofenac and lyophilized mucus (25 mg/kg) of rainbow trout, brook trout, European sea bass, and gilthead sea bream were administered to rats through gastric gavage 1 h before carrageenan treatment. Rat paws were measured before and 1-4 h after carrageenan treatment. The mRNA expressions of cytokines (TNF-α, IL-1β, IL-6, IL-10, and TGF-β), antioxidant markers (catalase and superoxide dismutase), and COX-2 were investigated using quantitative polymerase chain reaction. The histopathological changes were evaluated by hematoxylin and eosin staining. Results: The inhibition percentage of carrageenan-induced paw edema by different fish mucus ranged from 52.46% to 74.86% at 4 h. Histopathological evaluation showed that all fish mucus diminished carrageenan-induced edema and inflammatory cell infiltration. The upregulation of IL-1β mRNA induced by carrageenan was decreased by the mucus of rainbow trout and gilthead sea bream while an increase in the expression of IL-6 mRNA was reduced by the mucus of rainbow trout, brook trout, and gilthead sea bream. In addition, the mRNA expression of superoxide dismutase was higher in the rainbow trout mucus group than the carrageenan group. Conclusions: Mucus obtained from different fish species may have anti-inflammatory effects.

Antimicrobial and anti-inflammatory activities of three halophyte plants from Algeria and detection of some biomolecules by HPLC-DAD

Antimicrobial activity of hydroalcoholic extracts (30/70) from leaves and stems of three halophytes (Tamarix africana, Arthrocnemum macrostachyum and Suaeda fruticose) was investigated. In vivo toxicological study and anti-inflammatory activity of leaf extract of T. africana were tested on carrageenan-induced inflammatory paw edema. T. africana possessed significant anti-inflammatory activity at 150 and 300 mg/kg confirmed by histological study of inflamed tissues. Six phenolic acids and 10 flavonoids where identified by HPLC–DAD. Gallic acid, Rutin and Kaempferol-3-O-glucoside were the major compounds. For the antibiotic assays, S. fruticosa leaf extract exhibited strong bactericidal power against S. aureus with MBC of 1.25 mg/mL whereas T. africana leaf and stem samples exhibited a significant bactericidal activity against S. aureus and B. subtilis compared to the negative control (Ampicillin and Chloramphenicol). Crude leaf and stem extracts from T. africana and stem extract from S. fruticosa exhibited a strong antifungal effect against C. albicans.

Evaluation of the central and peripheral effects of doxepin on carrageenan-induced inflammatory paw edema in rat.

The anti-inflammatory effects of anti-depressants have been demonstrated recently. Doxepin, a tricyclic antidepressant drug (TCA), has some special properties in comparison with the other members of its family. It has some H1, H2, alpha-1 adrenergic and muscarinic receptor blocking effects. It revealed also anti-nociceptive and relatively potent sedative effects. This study was aimed to evaluate its possible anti-inflammatory effect in a well-established animal model. Male Wistar rats weighing 200-250 g were used in carrageenan-induced inflammatory paw edema model. The test and control drugs were injected by intraperitoneal (i.p.) and intracerebral (i.c.v.) routes. The anti-inflammatory activity of doxepin (15, 30 and 60 mg/kg, i.p. and 50 and 100 μg/rat, i.c.v.) and the reference drug, dexamethasone (2 mg/kg, i.p.) were evaluated by determination and comparison of some involved biological markers including the paw volume, cytokine levels (interleukin 6 (IL-6), IL-1β, tumor necrosis factor α (TNFα)), myeloperoxidase (MPO) activity and histopathological parameters. All i.p. doses of doxepin showed significant anti-inflammatory effect. It also significantly reduced MPO activity and cytokine levels and improved histopathologic parameters of carrageenan-injected paw tissues. I.c.v. administration of the drug did not show any significant reduction of carrageenan-induced paw edema. Although the exact mechanism of the anti-inflammatory effect of doxepin is not clear, it seems that reduced leukocyte migration and pro-inflammatory cytokines play important role in its anti-inflammatory effect. Also central sites are not involved in the anti-inflammatory effect of the drug.

Effects of Cream Containing Ultralow Volume Radionuclides on Carrageenan- Induced Inflammatory Paw Edema in Mice

Low-dose irradiation activates antioxidative functions and inhibits oxidative damage. Although a wide range of health products have been developed using the activation of biological functions by low-dose irradiation, their effectiveness has not yet been confirmed. The purpose of this study was to determine whether cream containing ultralow volume radionuclides (UVR) protects against carrageenan-induced inflammatory paw edema in mice. Cream containing ultralow volume radionuclides (UVR-cream) or sham cream was applied to the right hind paw of mice and 50 μL of carrageenan was subsequently injected to the right hind paw. Results showed that carrageenan administration induced paw edema; however, application of UVR-cream significantly decreased paw volume at 4 hours. Application of UVR-cream produced slight improvement in carrageenan-induced paw edema compared with sham cream. However, no significant changes were observed in paw edema between sham cream and UVR-cream. Carrageenan administration significantly decreased catalase activity and total glutathione content in paw. No significant changes were observed in the catalase activity or t-GSH content in paw among carrageenan-only, sham cream, and UVR-cream. In conclusion, the effects of UVR-cream differed from the beneficial effects induced by lowdose irradiation, since application of the cream did not activate antioxidative functions.

Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation.

Low-dose irradiation induces various stimulating effects, especially activation of the biological defense system including antioxidative and immune functions. Oxidative stress induced by reactive oxygen species (ROS) can cause cell damage and death and can induce many types of diseases. This paper reviews new insights into inhibition of ROS-related diseases with low-dose irradiation or radon inhalation. X-irradiation (0.5 Gy) before or after carbon tetrachloride (CCl4) treatment inhibits hepatopathy in mice. X-irradiation (0.5 Gy) before ischemia-reperfusion injury or cold-induced brain injury also inhibits edema. These findings suggest that low-dose X-irradiation has antioxidative effects due to blocking the damage induced by free radicals or ROS. Moreover, radon inhalation increases superoxide dismutase activity in many organs and inhibits CCl4-induced hepatic and renal damage and streptozotocin-induced type I diabetes. These findings suggest that radon inhalation also has antioxidative effects. This antioxidative effect against CCl4-induced hepatopathy is comparable to treatment with ascorbic acid (vitamin C) at a dose of 500 mg/kg weight, or α-tocopherol (vitamin E) treatment at a dose of 300 mg/kg weight, and is due to activation of antioxidative functions. In addition, radon inhalation inhibits carrageenan-induced inflammatory paw edema, suggesting that radon inhalation has anti-inflammatory effects. Furthermore, radon inhalation inhibits formalin-induced inflammatory pain and chronic constriction injury-induced neuropathic pain, suggesting that radon inhalation relieves pain. Thus, low-dose irradiation very likely activates the defense systems in the body, and therefore, contributes to preventing or reducing ROS-related injuries, which are thought to involve peroxidation.

Anti-inflammatory effects and acute toxicity of hydroethanolic extract of Jacaranda decurrens roots in adult male rats

Ethnopharmacological relevanceJacaranda decurrens subsp. symmetrifoliolata Farias and Proença (Bignoniaceae) is a species traditionally used for the treatment of inflammatory diseases. However, until this moment, there is no scientific evidence of these effects. Aim of studyTo evaluate the anti-inflammatory effects of hydroethanolic root extract of Jacaranda decurrens in rats and to determine the safe of this plant after acute exposure. Materials and methodsThe acute toxicity of Jacaranda decurrens root extract (EJD) was evaluated by oral administration to male rats as single doses of 0; 500; 1000 or 2000mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in carrageenan-induced inflammatory paw edema and myeloperoxidase activity in male rats. ResultsNo signs of acute toxicity were observed, indicating that the LD50 is greater than 2000mg/kg. EJD (100 and 300mg/kg) significantly reduced edema formation and at higher dose, the reduction was similar to dexamethasone. A significant decrease in myeloperoxidase activity was also observed. ConclusionsThe present study shows that Jacaranda decurrens extract has anti-inflammatory properties in rats without causing acute toxicity. These properties observed may be due to the presence of bioactive constituents such as ursolic acid.

Effects of Olmesartan and Pioglitazone on Carrageenan Induced Inflammatory Paw Edema in Rats

Effects of Olmesartan and Pioglitazone on Carrageenan Induced Inflammatory Paw Edema in Rats

Anti-inflammatory effects of different extracts from three Salvia species

Salvia L. species have been used for the treatment of various inflammatory ailments in traditional medicine. In order to evaluate this ethnobotanical information, water, methanol, n-butanol, acetone, and chloroform extracts from 3 Salvia species (S. fruticosa, S. verticillata, and S. trichoclada) were screened for their anti-inflammatory activity using in vivo experimental models in rats. For this purpose a carrageenan-induced inflammatory paw edema model was used. All extracts demonstrated anti-inflammatory activities; however, n-butanol extract of Salvia fruticosa (syn. S. triloba), which is known as Turkish sage, was found to be the most active. It can be expected that the active flavonoids, phenolic acids, and terpenoids may be responsible for the anti-inflammatory activity of these plants.

Erratum to: Protective Effects of Radon Inhalation on Carrageenan-Induced Inflammatory Paw Edema in Mice

Control 2000Bq/m3 The online version of the original article can be found at http:// dx.doi.org/10.1007/s10753-011-9364-y. 1 Graduate School of Health Sciences, Okayama University, 5-1 Shikatacho 2-chome, Kita-ku, Okayama-shi, Okayama 700-8558, Japan 2 Ningyo-toge Environmental Engineering Center, JapanAtomic Energy Agency, 1550 Kagamino-cho, Tomata-gun, Okayama 708-0698, Japan 3 Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical, Sciences, Fukuyama University, 1-Gakuen-cho, Fukuyama-shi, Hiroshima 729-0292, Japan 4 Radiation Safety Research Center, Central Research Institute of Electric Power Industry, 2-11-1 Iwado-kita, Komae-shi, Tokyo 201-8511, Japan 5 To whom correspondence should be addressed at Graduate School of Health Sciences, Okayama University, 5-1 Shikata-cho 2-chome, Kita-ku, Okayama-shi, Okayama 700-8558, Japan. E-mail: yamaoka@md. okayama-u.ac.jp

Protective Effects of Radon Inhalation on Carrageenan-Induced Inflammatory Paw Edema in Mice

We assessed whether radon inhalation inhibited carrageenan-induced inflammation in mice. Carrageenan (1% v/v) was injected subcutaneously into paws of mice that had or had not inhaled approximately 2,000Bq/m(3) of radon for 24h. Radon inhalation significantly increased superoxide dismutase (SOD) and catalase activities and significantly decreased lipid peroxide levels in mouse paws, indicating that radon inhalation activates antioxidative functions. Carrageenan administration induced paw edema and significantly increased tumor necrosis factor-alpha (TNF-α) and nitric oxide in serum. However, radon inhalation significantly reduced carrageenan-induced paw edema. Serum TNF-α levels were lower in the radon-treated mice than in sham-treated mice. In addition, SOD and catalase activities in paws were significantly higher in the radon-treated mice than in the sham-treated mice. These findings indicated that radon inhalation had anti-inflammatory effects and inhibited carrageenan-induced inflammatory paw edema.

Dual Effects of Hyperprolactinemia on Carrageenan-Induced Inflammatory Paw Edema in Rats

Objectives: The effects of short-term 5-day and long-term 30-day hyperprolactinemia induced by domperidone (1.7 mg/kg/day, s.c.) or ectopic pituitary graft on the acute inflammatory response induced by carrageenan were evaluated in male rats. Both models of hyperprolactinemia effectively increased serum prolactin (PRL) levels. Methods: The volume in milliliters of inflammatory edema was measured by plethysmography 1, 2, 3, 4, 6, 8 and 24 h after carrageenan injection. The areas under the inflammatory time-response curves were compared. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. Results: In both domperidone-treated and pituitary graft-implanted animals, short-term 5-day hyperprolactinemia increased the inflammatory response, while long-term 30-day hyperprolactinemia had anti-inflammatory effects. Body weight was not affected by either short- or long-term hyperprolactinemia. Conclusion: These results show that PRL has biphasic effects on the carrageenan-induced inflammatory response.

Diazepam effects on carrageenan-induced inflammatory paw edema in rats: Role of nitric oxide

High doses of diazepam (10.0–20.0 mg/kg) were shown to reduce the volume of acute inflammatory paw edema in rats as a response to carrageenan administration. This effect was attributed to an action of diazepam on the peripheral-type benzodiazepine receptor (PBR) present in the adrenal and/or immune/inflammatory cells. The present study was undertaken to analyze the involvement of nitric oxide (NO) on the effects of diazepam on carrageenan-induced paw edema in rats (CIPE) and to look for the presence of PBR and inducible/constitutive NO synthases (NOS) on slices taken from the inflamed paws of diazepam-treated rats. For that, an acute inhibition of NO biosynthesis was achieved using 50.0 mg/kg Nω-nitro- l-arginine ( l-NAME), l-arginine (300.0 mg/kg), the true precursor of NO, and d-arginine (300.0 mg/kg), its false substrate, were also used. The following results were obtained: (1) diazepam (10.0 and 20.0 mg/kg) decreased CIPE values in a dose- and time-dependent way; (2) diazepam effects on CIPE were increased by l-NAME pretreatment; (3) treatment with l-arginine but not with d-arginine reverted at least in part the decrements of CIPE values observed after diazepam administration; (4) PBR were found in endothelial and inflammatory cells that migrated to the inflammatory site at the rat paw; (5) confocal microscopy showed the presence of both PBR and NOS in endothelial and inflammatory cells taken from inflamed paw tissues of rats treated with diazepam a finding not observed in tissues provided from rats treated with diazepam's control solution. These results suggest an important role for NO on the effects of diazepam on CIPE. Most probably, these effects reflect a direct action of diazepam on PBR present in the endothelium of the microvascular ambient and/or on immune/inflammatory cells. An action like that would lead, among other factors, to a decrease in NO, generated by NO synthase, and thus in the mechanisms responsible for CIPE.

Reduction of inflammation in rats by diazepam: tolerance development

High doses of diazepam (10–20 mg/kg) were shown to reduce the volume of acute carrageenan-induced inflammatory paw edema in rats. This effect was not observed after adrenalectomy or long-term use of similar doses of diazepam. The present experiment was undertaken to analyze the effects of long-term (21 daily injections) treatment with diazepam (10 mg/kg) on both carrageenan-induced paw edema (CIPE) and corticosterone serum levels. For comparison, the effects of a single and acute 10 mg/kg dose of diazepam were also analyzed. Results showed that: 1- long-term diazepam treatment induced no changes in CIPE values and corticosterone serum levels; 2- acute diazepam treatment reduced CIPE values and increased corticosterone serum levels; 3- the plasmatic levels of diazepam measured 1 hour after the single treatment or 1 hour after the last dose of long-term diazepam administration were not different. These results indicate the development of tolerance to diazepam effects on both CIPE and corticosterone serum levels and suggest a relevant role for corticosterone on diazepam-induced inhibition of acute inflammation. Data were discussed in the light of peripheral benzodiazepine receptor site (PBR) activation within adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE. Possible actions of diazepam on HPA axis activity and/or on cytokine network were also discussed.