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1.
Naunyn Schmiedebergs Arch Pharmacol ; 396(3): 469-484, 2023 03.
Article in English | MEDLINE | ID: mdl-36385686

ABSTRACT

The present study prepared, optimized, and characterized solid lipid microparticles that contained trans-anethole (SLMAN), evaluated their antiinflammatory activity in acute and chronic inflammation models, and investigated their effects on the gastric mucosa in arthritic rats. The microparticles were obtained by a hot homogenization process and characterized by physicochemical analyses. The acute inflammatory response was induced by an intradermal injection of 0.1 ml of carrageenan solution (200 µg) in the hind paw. The rats were treated orally with a single dose of SLMAN 1 h before induction of the inflammatory response. The chronic inflammatory response was induced by the subcutaneous application of 0.1 ml of complete Freund's adjuvant suspension (500 µg) in the hind paw. SLMAN was orally administered, starting on the day of arthritis induction, and continued for 21 days. The results showed that SLMAN was obtained with good encapsulation efficiency. Treatment with SLMAN at doses of 25 and 50 mg/kg was as effective as trans-anethole (AN) at a dose of 250 mg/kg on acute and chronic inflammatory responses. Histological analyses showed that treatment with SLMAN did not aggravate lesions in the gastric mucosa in arthritic rats. These results indicated that treatment with SLMAN at a dose that was 5-10 times lower than non-encapsulated AN exerted an inhibitory effect on acute and chronic inflammatory responses, suggesting the better bioavailability and efficacy of microencapsulated AN without aggravating lesions in the gastric mucosa in arthritic rats.


Subject(s)
Arthritis, Experimental , Rats , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Inflammation/drug therapy , Inflammation/pathology , Lipids
2.
Avicenna J Phytomed ; 12(4): 388-400, 2022.
Article in English | MEDLINE | ID: mdl-35782770

ABSTRACT

Objective: In the present study, the hepatoprotective effects of ß-myrcene (MYR) on acetaminophen-induced hepatotoxicity were investigated. Materials and Methods: A total of 40 Balb/c mice were randomly divided into five groups as follows: 1) Normal control group which received only carboxymethylcellulose (CMC), the vehicle used to dissolve acetaminophen (N-acetyl-p-aminophenol, APAP, paracetamol) and MYR; 2) APAP group which received a single dose of acetaminophen (250 mg/kg) orally on day 7; 3) Silymarin group which received 200 mg/kg/day of silymarin; and 4 and 5) pretreatment groups in which, mice were treated with 100 or 200 mg/kg/day of MYR. Liver and blood samples were collected to analyze serum aminotransferases, inflammatory response, oxidative stress markers, and histopathological insults. Results: Our results showed that MYR pretreatment attenuated liver damage and restored liver cells function and integrity as it decreased the leakage of serum aminotransferases (alanine and aspartate aminotransferases (ALT and AST, respectively)) into the blood (p<0.01). MYR treatment also reduced levels of myeloperoxidase (MPO) activity and nitric oxide (NO) (p<0.001). In addition, MYR pretreatment demonstrated significant antioxidant activity by decreasing malondialdehyde (MDA), reactive oxygen species (ROS), and reduced glutathione (GSH) levels (p<0.001). Furthermore, it restored the hepatic level of superoxide dismutase (SOD), catalase (CAT), and oxidized glutathione (GSSG) (p<0.001). Conclusion: For the first time, our results showed that MYR treatment significantly improved liver function by reducing oxidative stress and the inflammatory response induced by APAP.

3.
Saude e pesqui. (Impr.) ; 13(1): 115-122, jan/mar 2020.
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1099983

ABSTRACT

O objetivo deste estudo foi avaliar a mortalidade por diferentes tipos de cânceres em crianças de 0 a 4 anos, e a distribuição destes óbitos para as cinco regiões brasileiras. Os números de casos registrados e de óbitos foram provenientes do Instituto Nacional do Câncer (INCA) e Sistema de Informações sobre Mortalidade (SIM/DATASUS). As informações sobre nascidos vivos foram coletadas no SINASC. O período de análise foi de 1996 a 2017. Os tipos de neoplasias com maior número de óbitos notificados foram as leucemias e as neoplasias do Sistema Nervoso Central. O número de óbitos em crianças na faixa etária estudada por neoplasias malignas foram foi de 2.597 mortes, sendo as leucemias, as neoplasias do Sistema Nervoso Central e os neuroblastomas responsáveis por aproximadamente 70% destas mortes. A frequência de mortes em relação ao tipo de câncer indicou que as neoplasias do sistema nervoso central apresentam mortalidade de 36,27%; seguida por neuroblastomas com 32,13%; leucemias, com 29,31%; e neoplasias dos tecidos moles, 21,56%. As regiões Sudeste e Nordeste apresentaram maior número de casos. Os resultados desta pesquisa indicaram elevado número de casos de câncer e óbito de crianças de 0-4 anos, reforçando a necessidade de constantes investimentos para um melhor acesso destes pacientes ao sistema de saúde, considerando que diagnóstico e tratamento são importantes para a redução da mortalidade infantil.


Mortality by different types of cancer in 0 - 4 year-old children and its distribution for the five Brazilian regions are investigated. Method: number of registered cases and deaths were retrieved derived from the National Institute of Cancer (INCA) and from the Mortality Information System (SIM/DATASUS). Information on live births was retrieved from SINASC for the period of analysis between 1996 and 2017. Results: types of cancer with the highest number of deaths notified were leukemia and cancers of the Central Nervous System. Number of death in children within the age bracket, with malignant cancer, reached 2,597, with leukemia, cancers of the Central Nervous System and neuroblastomas causing approximately 70% of deaths. Frequency of deaths with regard to cancer type indicates that cancers of the central nervous system had a 36.27% of deaths, followed by neuroblastomas, with 32.13%, leukemias, with 29.31% and cancers of the soft tissues, with 21.65%. The southeastern and northeastern regions of Brazil had the highest indexes. Conclusions: Results reveal high incidence of cancer cases and deaths in 0 ­ 4 year-old children, requiring constant investments for better access of patients to health systems where diagnosis and treatment are essential for the decrease of child mortality.

4.
Inflammation ; 43(1): 193-203, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31631236

ABSTRACT

(-)-α-Bisabolol (BISA) is an unsaturated monocyclic sesquiterpenes compound, mainly found in the essential oil of chamomile (Matricaria chamomilla). It has been reported that this compound has several biological activities, but there are few studies evaluating the activity of this compound in the systemic inflammatory response in infectious processes. The aim of this study was to evaluate the effect of BISA on the inflammatory response and survival rate in a systemic infection model, and in vitro neutrophils phagocytic activity. BISA at concentration of 3, 10, 30, and 90 µg/ml did not presented in vitro cytotoxicity in MTT assay, and at concentrations of 1 and 3 µg/ml the BISA treatment increased in vitro phagocytic neutrophil activity. For the inflammatory response study, we verified the BISA treatment effect in a cecal ligation and puncture (CLP)-induced systemic infection model in mice; in this model, we demonstrate that BISA at dose of 100 mg/kg reduced the leukocyte recruitment in peritoneal cavity; at dose of 200 mg/kg, the NO concentration was increased in the peritoneal cavity. The bacteria CFU number was reduced in mice blood in the BISA treatment, at doses of 100 and 200 mg/kg. The BISA treatment at doses of 50 and 100 mg/kg increased the myeloperoxidase activity and reduction NO production in lung tissue of mice in CLP model. At dose of 100 mg/kg, the BISA treatment was able to reduce the mortality rate of mice submitted to CLP-induced sepsis and observed for 7 days. The results suggest an effect of BISA on inflammatory response, with activity on leukocyte chemotactic and NO production, in addition to increasing the survival rate of animals submitted to CLP model.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Inflammation/prevention & control , Monocyclic Sesquiterpenes/pharmacology , Neutrophils/drug effects , Phagocytosis/drug effects , Sepsis/drug therapy , Animals , Bacterial Load , Cells, Cultured , Chemotaxis, Leukocyte/drug effects , Disease Models, Animal , Female , Host-Pathogen Interactions , Inflammation/immunology , Inflammation/metabolism , Inflammation/microbiology , Lung/drug effects , Lung/immunology , Lung/metabolism , Lung/microbiology , Mice, Inbred C57BL , Neutrophils/immunology , Neutrophils/metabolism , Neutrophils/microbiology , Nitric Oxide/metabolism , Peritoneum/drug effects , Peritoneum/immunology , Peritoneum/metabolism , Peritoneum/microbiology , Sepsis/immunology , Sepsis/metabolism , Sepsis/microbiology
5.
Article in English | MEDLINE | ID: mdl-29743918

ABSTRACT

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 µg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine.

6.
Article in English | MEDLINE | ID: mdl-28717379

ABSTRACT

High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP.

7.
Am J Chin Med ; 45(3): 515-532, 2017.
Article in English | MEDLINE | ID: mdl-28359199

ABSTRACT

To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO. The livers were used to determine myeloperoxidase (MPO) activity, nitric oxide (NO) production and histological analysis. The effect of LGO on leukocyte migration was evaluated in vitro. Anti-oxidant activity was performed by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. LGO pretreatment decreased significantly the levels of ALT, AST and ALP compared with APAP group. MPO activity and NO production were decreased. The histopathological analysis showed an improved of hepatic lesions in mice after LGO pretreatment. LGO inhibited neutrophil migration and exhibited anti-oxidant activity. Our results suggest that LGO has protective activity against liver toxicity induced by paracetamol.


Subject(s)
Acetaminophen/adverse effects , Analgesics, Non-Narcotic/adverse effects , Antipyretics/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Cymbopogon/chemistry , Oils, Volatile/therapeutic use , Phytotherapy , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Disease Models, Animal , Male , Mice , Oils, Volatile/administration & dosage , Oils, Volatile/isolation & purification , Oils, Volatile/pharmacology
8.
Biomed Pharmacother ; 84: 1697-1704, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27847207

ABSTRACT

PURPOSE: The aim of this study was to evaluate the effect of Pogostemon cablin essential oil (PEO) on leukocyte behavior in the inflammatory response. METHODS AND RESULTS: PEO was analyzed using Gas Chromatography/Mass Spectrometry (GC/SM) and Nuclear Magnetic Resonance Spectroscopy (NMR) methods and showed predominance of patchoulol (38.50%), α-bulnesene (20.37%), α-guaiene (12.31%), seychellene (8.33%) and α-patchoulene (4.91%). PEO at concentrations of 1, 3, 10, 30, 60 and 90µg/ml reduced the in vitro neutrophil chemotaxis toward fMLP, and at concentrations of 3 and 10µg/ml, increased the phagocytic activity of neutrophils. Topical application of PEO in high concentrations promoted an increase of ear edema and myeloperoxidase (MPO) activity. However, the oral treatment with 100, 200 and 300mg/kg reduced leukocyte recruitment, nitric oxide (NO) production, and rolling and adherent leukocyte number in the microcirculation. CONCLUSION: PEO affects the leukocyte behavior, and the mechanism proposed of PEO seems to be, at least in part, involving the participation of NO and pro-inflammatory cytokines.


Subject(s)
Inflammation/pathology , Leukocytes/cytology , Sesquiterpenes/pharmacology , Acute Disease , Administration, Topical , Animals , Cell Adhesion/drug effects , Cell Survival/drug effects , Chemotaxis/drug effects , Edema/pathology , Exudates and Transudates , Gas Chromatography-Mass Spectrometry , Leukocyte Count , Leukocyte Rolling/drug effects , Leukocytes/drug effects , Male , Mice , Nitric Oxide/metabolism , Peritonitis/pathology , Peroxidase/metabolism , Phagocytosis/drug effects , Pogostemon , Sesquiterpenes/administration & dosage , Zymosan
9.
Article in English | MEDLINE | ID: mdl-25821491

ABSTRACT

This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3 g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO) activity and nitric oxide (NO) production and were also sectioned for histological analysis. No differences were observed for ALT, γ-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, γ-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon) restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals.

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