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2.
Naunyn Schmiedebergs Arch Pharmacol ; 393(10): 1835-1848, 2020 10.
Article in English | MEDLINE | ID: mdl-32415495

ABSTRACT

Hemorrhagic cystitis (HC) is the major dose-limiting adverse effect of the clinical use ifosfamide (IFOS). The incidence of this side effect can be as high as 75%. Mesna has been used to reduce the risk of HC, although 5% of patients who get IFOS treatment may still suffer from HC. In previous studies, our group demonstrated that α-phellandrene (α-PHE) possesses anti-inflammatory activity, which opens the door for its study in the attenuation of HC. The objective of this study was to investigate the potential uroprotective effect of the α-PHE in the mouse model of IFOS-induced HC. In order to analyze the reduction of the urothelial damage, the bladder wet weight, hemoglobin content, and the Evans blue dye extravasation from the bladder matrix were evaluated. To investigate the involvement of neutrophil migration and lipid peroxidation and involvement of enzymatic and endogenous non-enzymatic antioxidants, the tissue markers myeloperoxidase (MPO), malondialdehyde, nitrite/nitrate (NOx), superoxide dismutase (SOD), and reduced glutathione (GSH) were evaluated. TNF-α and IL-1ß were measured by ELISA immunoassay technique. The results show that pretreatment with α-PHE significantly reduced urothelial damage that was accompanied by a decrease in the activity of MPO, MDA, and NOx levels and prevention of the depletion of SOD and GSH in bladder tissues. In the assessment of cytokines, α-PHE was able to significantly reduce TNF-α level. However, it does not affect the activities of IL-1ß. These data confirm that α-PHE exerts potent anti-inflammatory properties and demonstrates that α-PHE represents a promising therapeutic option for this pathological condition.


Subject(s)
Cyclohexane Monoterpenes/therapeutic use , Cystitis/prevention & control , Hemorrhage/prevention & control , Ifosfamide/toxicity , Oxidative Stress/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents, Alkylating/toxicity , Cyclohexane Monoterpenes/pharmacology , Cystitis/chemically induced , Cystitis/metabolism , Dose-Response Relationship, Drug , Hemorrhage/chemically induced , Hemorrhage/metabolism , Male , Mice , Oxidative Stress/physiology , Tumor Necrosis Factor-alpha/metabolism
3.
Int J Biol Macromol ; 154: 319-328, 2020 Jul 01.
Article in English | MEDLINE | ID: mdl-32173441

ABSTRACT

This study aims to determine the antitumor potential of cashew gum in vitro and in vivo. The cashew gum (CG) structure is similar to already showed in literature. The cytotoxicity effect of CG was performed by MTT assay, and B16-F10 melanoma model was used to evaluate antitumor effect. The tumor inhibition was calculated based on tumor weight. Hematological, histopathological, FTIR, oxidative stress and Western Blot analysis were performed to elucidate the mechanism of inhibition and toxic effects. As results, CG did not demonstrate cytotoxicity in vitro, however showed a significant tumor inhibition in vivo, with about 36.9 to 43% of reduction in tumor mass, with no toxicity to organs. Animals treated with CG did not show toxicity in normal tissues, FTIR spectrum and oxidative stress analysis of the tumor tissue indicated that CG cause tumor inhibition with the presence of apoptosis morphotype cells, without alterations in the levels of antioxidants components. In addition, it was observed that CG reduced the expression of γH2AX without changing the expression of caspase-3. With this, we can suggest that this polymer can assist in the anticancer activity and/or decrease the side effects of standard drugs used in treatment of cancer.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Plant Extracts/pharmacology , Plant Gums/pharmacology , Anacardium/chemistry , Animals , Apoptosis/drug effects , Cell Line, Tumor , Female , Humans , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects
4.
Med Oral Patol Oral Cir Bucal ; 23(3): e269-e276, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29680842

ABSTRACT

BACKGROUND: Periodontitis is a chronic disease that due to an intense inflammatory response triggers systemic changes such as hepatic alterations. This study aimed to compare hepatic damage in rats that received experimental periodontitis at one or two periodontal sites with ligatures. MATERIAL AND METHODS: Eighteen rats were separated into three groups: control, without ligature; periodontitis 1, with one ligature; and periodontitis 2, with two ligatures. The following parameters were assessed: gingival bleeding index, probing pocket depth, tooth mobility, alveolar bone loss, malondialdehyde (MDA) and myeloperoxidase (MPO) activity in periodontal tissue; histopathological evaluation of hepatic tissue (steatosis score); glutathione levels (GSH), MDA, MPO, cholesterol and triglycerides in the liver; and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). RESULTS: Periodontal evaluation data showed that the periodontitis model worked well. The groups with periodontitis did not differ significantly in relation to MPO activity and MDA levels in the gingival samples, but they were significantly different when compared with the control group. Steatosis was observed in the histological analysis of the groups with periodontitis, but between the periodontitis groups, two ligatures did not cause increase in steatosis score. The levels of GSH, MDA, total cholesterol and triglycerides in the hepatic tissue were not altered between groups with periodontitis, but they showed significant differences in comparison with the control group. The activity of MPO in hepatic tissue and serum levels of AST and ALT did not present significant difference among the three groups. CONCLUSION: In conclusion, our results demonstrated that one or two ligatures inducing periodontitis were both sufficient to cause fatty liver. Steatosis caused by two ligatures did not present larger extension and severity than steatosis caused by one ligature.


Subject(s)
Fatty Liver/etiology , Periodontitis/complications , Animals , Female , Ligation , Periodontitis/etiology , Rats , Rats, Wistar
5.
J Periodontal Res ; 52(5): 883-892, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28504459

ABSTRACT

BACKGROUND AND OBJECTIVE: Periodontitis may promote harmful systemic effects such as changes in hepatic tissues. The purpose of this study was to investigate whether the steatosis and oxidative stress caused by experimental periodontitis are reversible in the liver. MATERIAL AND METHODS: Twenty-four rats were divided into three groups: control, periodontitis and P20-20 (20 days with experimental periodontitis and 20 days without experimental periodontitis, to verify the reversibility of hepatic injuries). The following parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, alveolar bone loss for periodontal tissues; liver weights, histopathological scores for steatosis, inflammation and necrosis in liver; glutathione, malondialdehyde, total cholesterol and triglyceride concentrations in hepatic tissues; and blood levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase, total cholesterol and random glucose. RESULTS: Gingival bleeding index, probing pocket depth, myeloperoxidase and alveolar bone loss parameters demonstrated the development of periodontitis. There was a significant reduction in the steatosis score of animals from the P20-20 group when compared with the periodontitis group. P20-20 group presented significantly higher glutathione (11 times) and lower malondialdehyde (nearly 23%), total cholesterol (both in blood and hepatic tissue) and triglyceride concentrations compared with the periodontitis group. For levels of aspartate aminotransferase, alanine aminotransferase, albumin, gamma-glutaryl transferase and random glucose, a significant difference between the groups was not observed. CONCLUSION: Our results demonstrate that the microvesicular steatosis caused by periodontitis in rats is reversible after removal of the ligature, which is associated with the increase in oxidative stress and lipid peroxidation in the liver.


Subject(s)
Fatty Liver/etiology , Fatty Liver/therapy , Ligation/methods , Oxidative Stress , Periodontitis/complications , Alanine Transaminase/blood , Alveolar Bone Loss/classification , Alveolar Bone Loss/pathology , Animals , Aspartate Aminotransferases/blood , Blood Glucose , Cholesterol/analysis , Cholesterol/blood , Disease Models, Animal , Fatty Liver/pathology , Female , Gingiva/pathology , Glutathione/analysis , Inflammation , Lipid Peroxidation , Liver/injuries , Liver/pathology , Malondialdehyde/analysis , Necrosis/pathology , Periodontal Index , Periodontal Pocket/pathology , Periodontitis/pathology , Peroxidase/metabolism , Rats , Rats, Wistar , Serum Albumin , Time Factors , Transaminases/blood , Triglycerides/analysis , gamma-Glutamyltransferase/blood
6.
Rev. bras. plantas med ; 18(1): 38-47, jan.-mar. 2016. tab, graf
Article in English | LILACS | ID: lil-780050

ABSTRACT

ABSTRACT Seeds of Acacia farnesiana are commonly sold in the local markets of northeastern Brazil as a therapeutic agent. The present work aimed to evaluate the anti-inflammatory and analgesic activities of proteins obtained from A. farnesiana seeds. Five different protein fractions (albumin, globulin, prolamin, acidic and basic glutelins) were obtained and investigated for the protein pattern, the presence of hemagglutinating and proteolytic activities. The globulin fraction (GLB) was also evaluated for anti-inflammatory and analgesic activities. Globulins reduced the paw edema induced by carrageenan in a dose-dependent manner, which was accompanied by a reduction of myeloperoxidase activity (p < 0.05). Additionally, GLB reduced the neutrophil peritoneal migration induced by carrageenan. However, GLB was not able to inhibit the edema triggered by dextran. Pre-treatment with globulins reduced the abdominal constrictions induced by acetic acid as well as the paw licking time induced by formalin (69.1% at first phase). However, it did not produce a significant antinociceptive effect in the hot plate test (55-56 °C). Treating the GLB with heat (at 100 °C for 30 min) abolished its anti-edematogenic and hemagglutinating activities. Our results showed that seeds from A. farnesiana are a source of proteins with anti-inflammatory and analgesic properties.


RESUMO Sementes de Acacia farnesiana são comumente vendidas em feiras locais no nordeste do Brasil como agente terapêutico. O presente trabalho objetivou avaliar as atividades antiinflamatória e antinociceptiva de proteínas obtidas de sementes de A. farnesiana. Cinco frações protéicas distintas (albuminas, globulinas, prolaminas, glutelinas ácidas e básicas) foram obtidas e investigadas quanto o perfil de proteínas, presença de atividade hemaglutinante e proteolítica. A fração globulina (GLB) também foi avaliada quanto a presença de atividade antiinflamatória e analgésica. Globulinas reduziram o edema de pata induzido por carragenina de modo dependente da dose que foi acompanhada da redução da atividade da mieloperoxidase (p < 0,05). Em adição, GLB reduziu a migração de neutrófilos para cavidade peritoneal induzida por carragenina. Entretanto, GLB não foi capaz de inibir o edema induzido por dextrana. O pré-tratamento com globulinas reduziu as contorções abdominais induzidas por ácido acético, bem como o tempo de lambedura da pata induzida por formalina (69.1% na primeira fase). Por outro lado, GLB não produziu um efeito antinociceptivo significante no teste de placa quente (55-56 °C). O pré-tratamento de GLB com calor (100 °C por 30 min) aboliu sua atividade anti-edematogênica e hemaglutinante. Nossos resultados mostraram que sementes de A. farnesiana são fonte de proteínas com propriedades antiinflamatórias e analgésicas.


Subject(s)
Acacia/classification , Analgesics/classification , Anti-Inflammatory Agents/classification , Nociception/classification , Lectins/analysis
7.
Braz J Med Biol Res ; 46(8): 708-14, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23969974

ABSTRACT

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1ß], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35 ± 9.8 mm(2)); increased levels of TNF-α, IL-1ß, and MDA (2311 ± 302.3 pg/mL, 901.9 ± 106.2 pg/mL, 121.1 ± 4.3 nmol/g, respectively); increased MPO activity (26.1 ± 3.8 U/mg); and reduced GSH levels (180.3 ± 21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77 ± 5.3 mm(2)); reduced TNF-α, IL-1ß, and MDA formation (1502 ± 150.2 pg/mL, 632.3 ± 43.4 pg/mL, 78.4 ± 7.6 nmol/g, respectively); lowered MPO activity (11.7 ± 2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9 ± 40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.


Subject(s)
Alendronate/antagonists & inhibitors , Gastric Mucosa/drug effects , Hydrogen Sulfide/pharmacology , Indicators and Reagents/pharmacology , Organothiophosphorus Compounds/pharmacology , Stomach Diseases/chemically induced , Analysis of Variance , Animals , Cystathionine gamma-Lyase/analysis , Diagnosis, Computer-Assisted , Diazoxide/administration & dosage , Female , Gastric Mucosa/pathology , Glutathione/analysis , Glyburide/administration & dosage , Interleukin-1beta/analysis , KATP Channels/pharmacology , Malondialdehyde/analysis , Peroxidase/analysis , Peroxidase/metabolism , Rats , Rats, Wistar , Stomach Diseases/enzymology , Stomach Diseases/pathology , Tumor Necrosis Factor-alpha/analysis
8.
Braz. j. med. biol. res ; 46(8): 708-714, ago. 2013. tab, graf
Article in English | LILACS | ID: lil-684527

ABSTRACT

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.


Subject(s)
Animals , Female , Rats , Alendronate/antagonists & inhibitors , Gastric Mucosa/drug effects , Hydrogen Sulfide/pharmacology , Indicators and Reagents/pharmacology , Organothiophosphorus Compounds/pharmacology , Stomach Diseases/chemically induced , Analysis of Variance , Cystathionine gamma-Lyase/analysis , Diagnosis, Computer-Assisted , Diazoxide/administration & dosage , Gastric Mucosa/pathology , Glutathione/analysis , Glyburide/administration & dosage , Interleukin-1beta/analysis , KATP Channels/pharmacology , Malondialdehyde/analysis , Peroxidase/analysis , Peroxidase/metabolism , Rats, Wistar , Stomach Diseases/enzymology , Stomach Diseases/pathology , Tumor Necrosis Factor-alpha/analysis
9.
Br J Pharmacol ; 153(4): 721-7, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18071300

ABSTRACT

BACKGROUND AND PURPOSE: Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the NO/cGMP/K(ATP) pathway in the protective effects of sildenafil against ethanol-induced gastric damage. EXPERIMENTAL APPROACH: Rats were treated with L-NAME (1 or 3 mg kg(-1), i.p.) or with L-arginine (200 mg kg(-1), i.p.) + L-NAME (3 mg kg(-1), i.p.), the guanylate cyclase inhibitor, ODQ (10 mg kg(-1), i.p.), glibenclamide (0.1, 0.3, 1 or 3 mg kg(-1), i.p.) or with glibenclamide (1 mg kg(-1), i.p.) + diazoxide (3 mg kg(-1), i.p.). After thirty minutes, the rats received sildenafil (1 mg kg(-1), by gavage), followed by intragastric instillation of absolute ethanol (4 ml kg(-1)) to induce gastric damage. One hour later, gastric damage (haemorrhagic or ulcerative lesions) was measured with a planimetry programme. Samples of stomach were also taken for histopathological assessment and for assays of tissue glutathione and haemoglobin. KEY RESULTS: Sildenafil significantly reduced ethanol-induced gastric damage in rats. L-NAME alone, without L-arginine, significantly reversed the protection afforded by sildenafil. Inhibition of guanylate cyclase by ODQ completely abolished the gastric protective effect of sildenafil against ethanol-induced gastric damage. Glibenclamide alone reversed sildenafil's gastric protective effect. However, glibenclamide plus diazoxide did not alter the effects of sildenafil. CONCLUSIONS: Sildenafil had a protective effect against ethanol-induced gastric damage through the activation of the NO/cGMP/K(ATP) pathway.


Subject(s)
Cyclic GMP/metabolism , Gastric Mucosa/drug effects , KATP Channels/metabolism , Nitric Oxide/metabolism , Peptic Ulcer Hemorrhage/prevention & control , Phosphodiesterase Inhibitors/pharmacology , Piperazines/pharmacology , Stomach Ulcer/prevention & control , Sulfones/pharmacology , Animals , Arginine/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism , Diazoxide/pharmacology , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Ethanol , Gastric Mucosa/enzymology , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Glutathione/metabolism , Glyburide/pharmacology , Guanylate Cyclase/antagonists & inhibitors , Guanylate Cyclase/metabolism , Hemoglobins/metabolism , KATP Channels/drug effects , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Oxadiazoles/pharmacology , Peptic Ulcer Hemorrhage/etiology , Peptic Ulcer Hemorrhage/metabolism , Peptic Ulcer Hemorrhage/pathology , Phosphodiesterase 5 Inhibitors , Phosphodiesterase Inhibitors/therapeutic use , Piperazines/therapeutic use , Potassium Channel Blockers/pharmacology , Purines/pharmacology , Purines/therapeutic use , Quinoxalines/pharmacology , Rats , Rats, Wistar , Signal Transduction/drug effects , Sildenafil Citrate , Stomach Ulcer/chemically induced , Stomach Ulcer/complications , Stomach Ulcer/metabolism , Stomach Ulcer/pathology , Sulfones/therapeutic use
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