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1.
J Ethnopharmacol ; 324: 117707, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38232858

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Casimirella ampla (Miers) (C. ampla) are extensively used in folk medicine. For a long time, rural communities have been using extracts from its roots for food and therapeutic purposes. The extract is rich in diterpenoid annonalide (Annona), which has antiophidic, anti-inflammatory and antinociceptive properties. Inflammation is the body's primary defense mechanism against cell damage and invasion by pathogens, which can trigger acute and chronic inflammatory processes. The first line of treatment for this condition consists of the use of non-steroidal anti-inflammatory drugs, but these have numerous associated collateral damages, based on scientific knowledge about diterpenoids from C. ampla, as well as their already reported antinociceptive and anti-inflammatory properties. AIMS OF THE STUDY: Evaluate the effect of Annona in classic models of inflammation and pain. MATERIALS AND METHODS: Animals were pretreated with Annona (0.1, 1.0 and 10 mg/kg), or Tween 80 (2%), or indomethacin (Indo) (10 mg/kg) orally in the paw edema tests induced by carrageenan (Cg), serotonin (5-HT), histamine, bradykinin, 48/80 and, prostaglandin E2 (PGE2), evaluating microscopic lesion scores, migration of leukocytes to the peritoneal cavity, concentration of myeloperoxide (MPO), malonyldialdehyde (MDA) and glutathione (GSH), abdominal contortion test by acetic acid and formalin test. RESULTS: Treatment with Annona compound at a dose of 0.1 mg/kg was more effective in reducing inflammatory, oxidant and nociceptive parameters, as it reduced paw edema induced by carrageenan, through different mediators and migration of inflammatory cells. Furthermore, it worked by reducing the concentration of MPO, MDA, preserving GSH levels and reducing nociception caused by formalin and acetic acid.


Subject(s)
Analgesics , Magnoliopsida , Animals , Carrageenan , Analgesics/adverse effects , Plant Extracts/adverse effects , Anti-Inflammatory Agents/adverse effects , Inflammation/drug therapy , Glutathione/metabolism , Magnoliopsida/metabolism , Acetates , Edema/chemically induced , Edema/drug therapy , Edema/metabolism
2.
Int J Biol Macromol ; 232: 123058, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-36669633

ABSTRACT

Lemon gum (LG) obtained from Citrus × latifolia in Brazil was isolated and characterized. In addition, gum biocompatibility was evaluated in vitro and in vivo by Galleria mellonella and mice model. The cytotoxicity against tumor cells was also evaluated. The ratio of arabinose:galactose: rhamnose:4-OMe-glucuronic acid was 1:0.65:0.06:0.15. Small traces of protein were detected, emphasizing the isolate purity. Molar mass was 8.08 × 105 g/mol, with three different degradation events. LG showed antiproliferative activity against human prostate adenocarcinoma cancer cells, with percentage superior to 50 %. In vivo toxicity models demonstrated that LG is biocompatible polymer, with little difference in the parameters compared to control group. These results demonstrate advance in the study of LG composition and toxicity, indicating a potential for several biomedical and biotechnological future applications.


Subject(s)
Adenocarcinoma , Citrus , Male , Animals , Mice , Humans , Prostate , Galactans , Adenocarcinoma/drug therapy
3.
Cytokine ; 157: 155955, 2022 09.
Article in English | MEDLINE | ID: mdl-35792283

ABSTRACT

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.


Subject(s)
Dengue , Virus Diseases , Bayes Theorem , Dengue/genetics , Genetic Predisposition to Disease/genetics , Humans , Meta-Analysis as Topic , Polymorphism, Genetic/genetics
4.
Lasers Med Sci ; 37(1): 563-571, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33788097

ABSTRACT

Photobiomodulation therapy (PBMT) is a non-thermal therapeutic procedure widely used in clinical practice. It is considered an effective modality of treatment for the control of various inflammatory conditions with fewer adverse effects as compared to conventional therapy. However, despite the clinical effects, the mechanisms of action and dosimetric parameters of PBMT are not fully understood. This study was performed to describe the effects of two different doses of PBMT on experimental models of inflammation. Male Swiss mice were administered with 0.9% of saline or phlogistic agents (carrageenan, dextran, serotonin, histamine, or bradykinin) by intra-plantar injection and were treated with PBMT at a dose of 1 or 5 J/cm2; right after, the variation of the paw volume was made, and histopathological analysis and myeloperoxidase assay of the carrageenan-induced edematous paw tissues were performed. The action of PBMT on carrageenan-induced vascular permeability was further evaluated. Our results showed that PBMT (1 J/cm2) led to an improvement in paw edema induced by the phlogistic agents and further reduced the histological scores. Inhibition of neutrophil migration was observed following the administration of 1 and 5 J/cm2 of PBMT. However, only 1 J/cm2 of PBMT showed beneficial effects on carrageenan-induced edema. Laser at a dose of 1 J/cm2 showed cellular and vascular effects since it was able to reverse all the inflammatory parameters, and laser at a dose of 5 J/cm2 probably has only cellular effects in the presence of acute inflammation.


Subject(s)
Low-Level Light Therapy , Animals , Anti-Inflammatory Agents/therapeutic use , Edema/chemically induced , Inflammation/radiotherapy , Male , Mice , Models, Theoretical , Rats , Rats, Wistar
5.
J Periodontol ; 93(1): 156-165, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33856704

ABSTRACT

BACKGROUND: Periodontitis is a chronic inflammatory and multifactorial disease that affects the periodontal structures and can cause alterations in the hepatic tissue. The aim of the present study was to evaluate whether a diet with food restriction can decrease oral and liver alterations associated with ligature-induced periodontitis. METHODS: Twenty-four female Wistar rats were used in this study, randomized into three groups (n = 8 for each group): control (regular food); periodontitis (regular food + periodontitis induced with ligatures); and food restriction (diet with food restriction and periodontitis induction). The following periodontium parameters were analyzed tooth mobility (TM), probing pocket depth (PPD), gingival bleeding index (GBI), and alveolar bone height (ABH). In the liver, the levels of oxidative stress markers-malondialdehyde (MDA), glutathione (GSH), total cholesterol, and levels of myeloperoxidase (MPO) activity were measured. Liver samples were analyzed for histopathological score. In the blood tissue, the levels of enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, and the high-density lipoprotein (HDL) were also evaluated. RESULTS: The animals that received a diet with food restriction + periodontitis showed a decrease in hepatic histopathological score (P < 0.05) when compared with the periodontitis group, the same for glucose, total cholesterol, ALT, AST, and ABH data. The group with food restriction + periodontitis showed a decrease in the histopathological liver score (P < 0.05) compared with the group with periodontitis. CONCLUSION: This study revealed that food restriction reduced oral damages, as well as hepatic, blood and alveolar bone alterations associated with ligature-induced periodontitis in rats.


Subject(s)
Alveolar Bone Loss , Periodontitis , Alveolar Bone Loss/etiology , Alveolar Bone Loss/prevention & control , Animals , Cholesterol , Female , Glucose , Glutathione , Liver/pathology , Periodontitis/complications , Rats , Rats, Wistar
6.
Life Sci ; 272: 119194, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33609541

ABSTRACT

AIM: The aim of the present study was to investigate the anti-inflammatory response mediated of the M1 muscarinic acetylcholine receptor (mAChR) during experimental colitis. MATERIAL AND METHODS: After the induction of 6% acetic acid colitis, mice were treated with McN-A-343 0.5, 1.0, and 1.5 mg/kg or dexamethasone (DEXA, 2.0 mg/kg) or pirenzepine (PIR, 10 mg/kg; M1 mAChR antagonist). Colonic inflammation was assessed by macroscopic and microscopic lesion scores, colonic wet weight, myeloperoxidase (MPO) activity, interleukin-1 beta (IL1-ß) levels and tumor necrosis factor alpha (TNF-α), glutathione (GSH), malondialdehyde (MDA) and nitrate and nitrite (NO3/NO2), mRNA expression of IKKα, nuclear factor kappa beta (NF-kB) and cyclooxygenase-2 (COX-2), as well protein expression of NF-kB and COX-2. RESULTS: Treatment with McN-A-343 at a concentration of 1.5 mg/kg showed a significant reduction in intestinal damage as well as a decrease in wet weight, MPO activity, pro-inflammatory cytokine concentration, markers of oxidative stress and expression of inflammatory mediators. The action of the M1 agonist by the administration of pirenzepine, which promoted the blocking of the mAChR M1-mediated anti-inflammatory response, has also been proven. CONCLUSION: The results suggest that peripheral colonic M1 mAChR is involved in reversing the pro-inflammatory effect of experimentally induced colitis, which may represent a promising therapeutic alternative for patients with ulcerative colitis.


Subject(s)
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride/pharmacology , Colitis, Ulcerative/drug therapy , (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride/metabolism , Animals , Colitis/drug therapy , Colitis/metabolism , Colitis, Ulcerative/metabolism , Colon/metabolism , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Dexamethasone/pharmacology , Disease Models, Animal , Glutathione/metabolism , Inflammation/pathology , Inflammation Mediators/metabolism , Interleukin-1beta/metabolism , Male , Malondialdehyde/metabolism , Mice , Muscarinic Agonists/pharmacology , NF-kappa B/metabolism , Oxidative Stress/drug effects , Receptor, Muscarinic M1 , Tumor Necrosis Factor-alpha/metabolism
7.
J Periodontal Res ; 56(2): 306-313, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33296521

ABSTRACT

BACKGROUND AND OBJECTIVE: Periodontitis may crosstalk with renal diseases, yet that remains unclear. We investigated whether the renal alterations caused by induced periodontitis are reversible after removal of the ligatures in experimental ligature-induced periodontitis. MATERIAL AND METHODS: Twenty-four female rats were divided into three groups: control (without periodontitis), periodontitis (20 days of ligature-induced periodontitis), and P20-20 (20 days of ligature-induced periodontitis and 20 days after ligature removal). The following periodontal parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, and alveolar bone height. For renal tissues, histopathology, malonaldehyde (MDA) levels, glutathione (GSH) content, and renal weight were evaluated. In the blood, creatinine, uric acid, albumin, total cholesterol, total protein, and glucose levels were assessed. Total protein and creatinine levels in urine were also investigated. RESULTS: Rat renal tissues did not demonstrate reversal of periodontitis-related changes in the P20-20 group in terms of MDA, GSH, and histopathological evaluations when compared to the periodontitis group. Accordingly, only total cholesterol levels were reversible in the P20-20. CONCLUSION: Renal alterations caused by ligature-induced periodontitis persisted even after removal of ligatures in rats.


Subject(s)
Alveolar Bone Loss , Periodontitis , Alveolar Bone Loss/etiology , Animals , Female , Ligation , Malondialdehyde , Periodontitis/complications , Rats , Rats, Wistar
8.
Cytokine ; 138: 155361, 2021 02.
Article in English | MEDLINE | ID: mdl-33223448

ABSTRACT

Periodontitis is a high prevalent disease into the clinical dentistry. Genetic variations in interleukins (IL) genes were associated with chronic periodontitis (CP) and were focus of several meta-analyses. This study aimed to assess the noteworthiness in the meta-analyses by means of a Bayesian approach to determinate possible false report associations. A systematic search was performed for meta-analyses with associations between gene polymorphisms in interleukins and CP. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. As results, eight meta-analyses approaching the IL1A/rs1800587, IL1B/rs1143634, IL1RN/rs2234663, IL4/rs2243250, IL6/rs1800795/rs1800796, IL17A/rs2275913 and IL18/rs1946518/rs187238 polymorphisms have been identified. Twenty-two from 270 calculations (8.15%) were noteworthy. Herein, we have identified the IL1A and IL1B polymorphisms as noteworthy biomarkers for CP susceptibility.


Subject(s)
Chronic Periodontitis/genetics , Genetic Predisposition to Disease , Interleukin-1beta/genetics , Polymorphism, Single Nucleotide , Bayes Theorem , Biomarkers/metabolism , False Positive Reactions , Humans , Inflammation Mediators , Meta-Analysis as Topic , Odds Ratio , Probability
9.
Brain Sci ; 10(10)2020 Sep 30.
Article in English | MEDLINE | ID: mdl-33007889

ABSTRACT

This study aimed to verify noteworthy findings between genetic risk factors and autism spectrum disorder (ASD) by employing the false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP). PubMed and the Genome-Wide Association Studies (GWAS) catalog were searched from inception to 1 August, 2019. We included meta-analyses on genetic factors of ASD of any study design. Overall, twenty-seven meta-analyses articles from literature searches, and four manually added articles from the GWAS catalog were re-analyzed. This showed that five of 31 comparisons for meta-analyses of observational studies, 40 out of 203 comparisons for the GWAS meta-analyses, and 18 out of 20 comparisons for the GWAS catalog, respectively, had noteworthy estimations under both Bayesian approaches. In this study, we found noteworthy genetic comparisons highly related to an increased risk of ASD. Multiple genetic comparisons were shown to be associated with ASD risk; however, genuine associations should be carefully verified and understood.

10.
Mini Rev Med Chem ; 20(19): 2011-2018, 2020.
Article in English | MEDLINE | ID: mdl-32955001

ABSTRACT

Liver disease is global health problem. Paracetamol (APAP) is used as an analgesic drug and is considered safe at therapeutic doses, but at higher doses, it causes acute liver injury. N-acetyl-p- Benzoquinone Imine (NAPQI) is a reactive toxic metabolite produced by biotransformation of APAP. NAPQI damages the liver by oxidative stress and the formation of protein adducts. The glutathione precursor N-acetylcysteine (NAC) is the only approved antidote against APAP hepatotoxicity, but it has limited hepatoprotective effects. The search for new drugs and novel therapeutic intervention strategies increasingly includes testing plant extracts and other natural products. Plumeria pudica (Jacq., 1760) is a plant that produces latex containing molecules with therapeutic potential. Proteins obtained from this latex (LPPp), a well-defined mixture of chitinases, proteinases proteinase inhibitors have shown anti-inflammatory, antinociceptive, antidiarrheal effects as well as a protective effect against ulcerative colitis. These studies have demonstrated that LPPp acts on parameters such as Glutathione (GSH) and Malondialdehyde (MDA) concentration, Superoxide Dismutase (SOD) activity, Myeloperoxidase (MPO) activity, and TNF- α IL1-ß levels. Since oxidative stress and inflammation have been reported to affect the initiation and progression of liver injury caused by APAP, it is suggested that LPPp can act on aspects related to paracetamol hepatoxicity. This article brings new insights into the potential of the laticifer proteins extracted from the latex of P. pudica and opens new perspectives for the treatment of this type of liver disease with LPPp.


Subject(s)
Apocynaceae/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Latex/metabolism , Plant Proteins/therapeutic use , Acetaminophen/administration & dosage , Acetaminophen/adverse effects , Animals , Chemical and Drug Induced Liver Injury/etiology , Cytokines/metabolism , Liver/drug effects , Liver/metabolism , Plant Extracts/metabolism , Plant Proteins/isolation & purification , Plant Proteins/pharmacology , Protective Agents/isolation & purification , Protective Agents/pharmacology , Protective Agents/therapeutic use
11.
J Periodontal Res ; 55(6): 877-886, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32583890

ABSTRACT

BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS: The treatment with αTPN-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION: The results obtained suggest that the treatment with αTPN-ßCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-ßCD.


Subject(s)
Alveolar Bone Loss , Cyclohexane Monoterpenes , Periodontitis , beta-Cyclodextrins , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/prevention & control , Animals , Cyclohexane Monoterpenes/pharmacology , Female , Ligation , Periodontitis/drug therapy , Rats
12.
Oral Dis ; 26(8): 1793-1802, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32531862

ABSTRACT

OBJECTIVE: The objective of this research was to evaluate the effects of bromelain (derived from Ananas comosus) upon periodontitis in rats. MATERIALS AND METHODS: Twenty-four rats were separated into groups: control, periodontitis, and bromelain treatment. Bromelain was administered daily by intraperitoneal injection for 20 days. Periodontitis was induced by ligature around the first molars. Oral parameters and blood biomarkers were measured. The histopathological evaluation of the hepatic tissue was performed. Bromelain treatment significantly reduced several oral inflammatory parameters, alveolar bone loss, and blood biomarkers compared to the rats on periodontitis. RESULTS: Treatment with bromelain improved the steatosis score. Bromelain used in ligature-induced periodontitis in rats was able to reduce the oral inflammatory parameters Gingival Bleeding Index (GBI), tooth mobility (TM), probing pocket depth (PPD), malondialdehyde (MDA), alveolar bone height (ABH) and gingival myeloperoxidase (MPO) and blood parameters (cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase). Bromelain treatment reduced the impact of periodontitis, such as the reduction of hepatic steatosis and improvement in the dosages of MDA and GSH. CONCLUSION: Bromelain acts as a potential adjunct in the non-surgical treatment of periodontitis and, consequently, reduces the impact of periodontitis, acting as anti-inflammatory and antioxidant.


Subject(s)
Alveolar Bone Loss , Non-alcoholic Fatty Liver Disease , Periodontitis , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/etiology , Alveolar Bone Loss/prevention & control , Animals , Bromelains/pharmacology , Bromelains/therapeutic use , Non-alcoholic Fatty Liver Disease/drug therapy , Periodontitis/drug therapy , Rats , Rats, Wistar
13.
Med Hypotheses ; 139: 109613, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32085982

ABSTRACT

Inflammatory Bowel Disease (IBD) is idiopathic, chronic and affects the gastrointestinal tract. It results from the association of genetic, environmental and immune deregulation, which culminates in the development and progression of the inflammatory process. In an attempt to reverse colonic inflammation, endogenous systems involved in intestinal physiology are studied and the cholinergic system is fundamental for this process. In addition, this system has anti-inflammatory action in experimental models of IBD. Another important endogenous system in regulating the exacerbated inflammatory response in the gut is mediated by endocannabinoids, which play an important role in restoring bowel functionality after the onset of the inflammatory process. There are several reports in the literature showing the interconnection between the cannabinoid and cholinergic systems in different tissues. Considering that the activation of the cholinergic system stimulates the production of cannabinoid agonists in the intestine, our hypothesis is that the interaction between the muscarinic system and the cannabinoid in the control of intestinal inflammation is mediated by endogenous cannabinoids, since they are stimulated by the activation of muscarinic receptors.


Subject(s)
Cannabinoid Receptor Agonists , Cannabinoids , Inflammation , Intestinal Diseases , Cholinergic Agents , Endocannabinoids , Humans , Intestinal Diseases/metabolism , Receptors, Cannabinoid
14.
BMC Oral Health ; 20(1): 58, 2020 02 19.
Article in English | MEDLINE | ID: mdl-32075624

ABSTRACT

BACKGROUND: Chronic periodontitis (CP) is an immune-inflammatory disease that promotes tissue damage around the teeth. Among the several inflammatory mediators that orchestrate the periodontitis, there is the interleukin (IL)-2. Genetic variations in IL2 gene may be associated with the risk and severity of the disease. Contrary results are available in the literature with inconclusive findings and none meta-analysis to gather these data. METHODS: A literature search was performed for studies published before June 11, 2019 in diverse scientific and educational databases. The data was extracted by two investigators and the statistical evaluation was performed by Review Manager statistical program with heterogeneity (I2) and Odds Ratio (OR) with 95% of Confidence Intervals (CI) calculations and a sensitive analysis to assess the accuracy of the obtained results. The publication bias was evaluated by Begg' and Egger's test with Comprehensive meta-analysis software. The value of P < 0.05 was considered as significant. RESULTS: Five studies were identified in diverse ethnical groups with 1425 participants. The - 330 T/G polymorphism in IL2 gene was not significantly associated with CP in allelic evaluation (P > 0.05) as well as in the genotypic comparisons (P = 0.15). The Begg's test and the linear regression Egger's test did not show any evidence of publication bias risk (P > 0.05) which was corroborated by the absence of obvious asymmetry in Funnel plot graphic. CONCLUSIONS: This meta-analysis showed a non-significant association between - 330 T/G polymorphism in IL2 gene and CP in any allelic evaluation.


Subject(s)
Chronic Periodontitis/genetics , Genetic Predisposition to Disease/genetics , Interleukin-2/genetics , Alleles , Genetic Predisposition to Disease/ethnology , Humans , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Risk Factors
15.
Eur J Pharmacol ; 873: 172974, 2020 Apr 15.
Article in English | MEDLINE | ID: mdl-32027888

ABSTRACT

Gabapentin is an anticonvulsant drug that is also used for post-herpetic neuralgia and neuropathic pain. Recently, gabapentin showed anti-inflammatory effect. Nuclear factor kappa B (NFκB) is a regulator of the inflammatory process, and Peroxisome Proliferator-activated Receptor gamma (PPAR-gamma) is an important receptor involved in NFκB regulation. The aim of the present work was to study the potential role of PPAR-gamma receptor in gabapentin-mediated anti-inflammatory effects in a colitis experimental model. We induced colitis in rats using trinitrobenzenosulfonic acid and treated them with gabapentin and bisphenol A dicyldidyl ether (PPAR-gamma inhibitor). Macroscopic lesion scores, wet weight, histopathological analysis, mast cell count, myeloperoxidase, malondialdehyde acid, glutathione, nitrate/nitrite, and interleukin levels in the intestinal mucosa were determined. In addition, western blots were performed to determine the expression of Cyclooxygenase-2 (COX-2) and NFκB; Nitric Oxide Inducible Synthase (iNOS) and Interleukin 1 beta (IL-1ß) levels were also determined. Gabapentin was able to decrease all inflammatory parameters macroscopic and microscopic in addition to reducing markers of oxidative stress and cytokines such as IL-1ß and Tumor Necrosis Factor alpha (TNF-α) as well as enzymes inducible nitric oxide synthase and cyclooxygenase 2 and inflammatory genic regulator (NFκB). These effect attributed to gabapentin was observed to be lost in the presence of the specific inhibitor of PPAR-gamma. Gabapentin inhibits bowel inflammation by regulating mast cell signaling. Furthermore, it activates the PPAR-gamma receptor, which in turn inhibits the activation of NFκB, and consequently results in reduced activation of inflammatory genes involved in inflammatory bowel diseases.


Subject(s)
Colitis/drug therapy , Gabapentin/therapeutic use , PPAR gamma/drug effects , Animals , Benzhydryl Compounds/therapeutic use , Colitis/chemically induced , Colitis/pathology , Cytokines/metabolism , Glutathione/metabolism , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Male , Malondialdehyde/metabolism , Mast Cells/drug effects , NF-kappa B/metabolism , PPAR gamma/antagonists & inhibitors , Peroxidase/metabolism , Phenols/therapeutic use , Rats , Rats, Wistar , Signal Transduction/drug effects , Trinitrobenzenesulfonic Acid
16.
J Ethnopharmacol ; 248: 112303, 2020 Feb 10.
Article in English | MEDLINE | ID: mdl-31614204

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: There are many reports of pharmacological activities of extracts and fractions of different vegetable-derived products in the scientific literature and in folk medicine. Ethnopharmacological use of these products by various communities continues to be extensively explored, and they account for more than half of all medications used worldwide. Polysaccharides (PLS) extracted from plants such as Morinda Citrifolia Linn present therapeutic potential in treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). AIM OF THE STUDY: To evaluate the anti-inflammatory action of Noni-PLS against the intestinal damage in UC induced by acetic acid in mice. MATERIALS AND METHODS: In acetic acid-induced colitis, the mice were treated intraperitoneally (ip) with Noni-PLS (0.1, 0.3, and 3.0 mg/kg) or subcutaneously (sc) with dexamethasone (2.0 mg/kg) 30 min before euthanasia to determine the best dose of Noni-PLS with an anti-inflammatory effect in the course of UC. The colonic tissue samples were collected for macroscopic, wet weight, microscopic and biochemical (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), nitrate/nitrite (NO3/NO2), cytokines, cyclooxygenase (COX-2) and inducible nitric oxide (iNOS)) analyses. RESULTS: Treatment with Noni-PLS reduced the intestinal damage induced by acetic acid as it reduced macroscopic and microscopic scores and the wet weight of the colon. In addition, MPO activity and levels of GSH, MDA, NO3/NO2, pro-inflammatory cytokines, and COX-2 expression reduced. CONCLUSIONS: This study suggests that Noni-PLS exhibits anti-inflammatory action against intestinal damage by reducing inflammatory cell infiltration, oxidative stress, pro-inflammatory action of cytokines, COX-2 and iNOS expression in the inflamed colon. Noni-PLS shows therapeutic potential against inflammatory disorders like UC.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis/drug therapy , Morinda , Polysaccharides/therapeutic use , Acetic Acid , Animals , Anti-Inflammatory Agents/pharmacology , Colitis/chemically induced , Colitis/metabolism , Colitis/pathology , Colon/drug effects , Colon/metabolism , Colon/pathology , Cyclooxygenase 2/metabolism , Fruit , Glutathione/metabolism , Interleukin-1beta/metabolism , Male , Malondialdehyde/metabolism , Mice , Nitrates/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitrites/metabolism , Peroxidase/metabolism , Polysaccharides/pharmacology , Tumor Necrosis Factor-alpha/metabolism
17.
Life Sci ; 231: 116535, 2019 Aug 15.
Article in English | MEDLINE | ID: mdl-31175857

ABSTRACT

Latex proteins from P. pudica (LPPp) have anti-inflammatory activity. In the present study, LPPp was evaluated to protect animals against inflammatory ulcerative colitis (UC). UC was induced by intracolonic instillation of a 6% acetic acid solution and the animals received LPPp (10, 20 or 40 mg/kg) by intraperitoneal route 1 h before and 17 h after acetic acid injection. Eighteen hours after instillation of acetic acid, the mice were euthanized and the colons were excised to determine the wet weight, macroscopic and microscopic lesion scores, myeloperoxidase (MPO) activity, IL1-ß levels, glutathione (GSH) and malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity. The results revealed that LPPp treatment (40 mg/kg) had a protective effect on acetic acid-induced colitis by reducing the wet weight, macroscopic and microscopic scores of intestinal lesions and colonic MPO activity. Additionally, LPPp inhibited tissue oxidative stress, since decreases in GSH consumption, MDA concentration and SOD activity were observed. The treatment with LPPp reduced the levels of cytokine IL-1ß, contributing to the reduction of colon inflammation. Biochemical investigation showed that LPPp comprises a mixture of proteins containing proteinases, chitinases and proteinase inhibitors. These data suggest that LPPp has a protective effect against intestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration, cytokine release and oxidative stress.


Subject(s)
Apocynaceae/chemistry , Colitis/drug therapy , Latex/pharmacology , Plant Proteins/pharmacology , Acetic Acid , Animals , Apocynaceae/metabolism , Colitis/chemically induced , Colitis/metabolism , Colon/drug effects , Cytokines/metabolism , Glutathione/metabolism , Inflammation/drug therapy , Interleukin-1beta/metabolism , Intestines/pathology , Latex/isolation & purification , Male , Mice , Oxidative Stress/drug effects , Plant Proteins/isolation & purification , Protective Agents/pharmacology , Tumor Necrosis Factor-alpha/metabolism
18.
Genet Test Mol Biomarkers ; 23(4): 255-263, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30986096

ABSTRACT

AIMS: Periodontitis results from the presence of periodontopathogenic bacterial activity in the region of the gingival sulcus promoting tissue degradation and alveolar bone resorption. Biochemical analysis of the saliva can be used as a less invasive method for disease prognosis. This study aimed to evaluate the relationship between biochemical protein levels in the saliva sample of patients with chronic periodontitis and healthy patients. MATERIALS AND METHODS: A literature review was performed using electronic databases (Cochrane Library, Google Scholar, MEDLINE, PubMed, and Web of Science) for studies published before July 2, 2016. The abstracts were evaluated, and the data extraction was performed by two calibrated examiners. The mean difference, and heterogeneity were calculated, and funnel plots were produced. RESULTS: Twenty case-control studies were selected with 2436 patients with chronic periodontitis and 1787 controls. The meta-analysis showed that increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and acid phosphatase (ACP) were all associated with periodontitis (p < 0.05), while blood urea nitrogen (BUN) and osteoprotegerin (OPG) levels did not show statistical differences between cases and controls (p > 0.05). CONCLUSIONS: This meta-analysis evidenced that increased levels of AST, ALT, CK, gama glutamil transferase (GGT), LDH, ALP, and ACP are associated in patients with chronic periodontitis, while BUN and OPG level in saliva did not present differences between groups.


Subject(s)
Chronic Periodontitis/metabolism , Chronic Periodontitis/physiopathology , Acid Phosphatase/analysis , Acid Phosphatase/blood , Adult , Alanine Transaminase/analysis , Alanine Transaminase/blood , Alkaline Phosphatase/analysis , Alkaline Phosphatase/blood , Aspartate Aminotransferases/analysis , Aspartate Aminotransferases/blood , Case-Control Studies , Creatine Kinase/analysis , Creatine Kinase/blood , Female , Humans , L-Lactate Dehydrogenase/analysis , L-Lactate Dehydrogenase/blood , Male , Saliva/chemistry
19.
Int J Biol Macromol ; 132: 1-8, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30926484

ABSTRACT

Sulfated polysaccharides (PLS) extracted from the marine algae of the genus Gracilaria showed biological activity in different inflammatory models, except for periodontitis. Thus, this study aimed to evaluate the effectiveness of the treatment with PLS from Gracilaria caudata in ligature-induced periodontitis. 40 animals distributed into 5 groups were used (the control group (unligated), the ligated untreated group, and the ligated groups treated with 2.5, 5.0 and 10.0 mg/kg of PLS with intraperitoneal injection, respectively). After 20 days of treatment, the animals were killed and the following parameters were evaluated: Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), Myeloperoxidase (MPO) activity, Alveolar Bone Loss (ABL) for periodontal tissues; histopathological examination of gingival and liver tissues (Steatosis score); glutathione and malondialdehyde concentrations in the liver, serum levels of alanine aminotransferase and aspartate aminotransferase. The data revealed that treatment with 2.5 mg/kg of PLS showed the best anti-inflammatory effects with reduction of GBI, PPD and MPO activity, as well as oxidative stress and steatosis in liver. Our results indicated that the adjunct treatment with PLS from Gracilaria caudata could prevent the periodontal and hepatic tissue alteration caused by periodontitis.


Subject(s)
Gracilaria/chemistry , Periodontitis/pathology , Polysaccharides/chemistry , Polysaccharides/pharmacology , Sulfates/chemistry , Animals , Biomarkers/metabolism , Cytoprotection/drug effects , Female , Ligation/adverse effects , Liver/drug effects , Liver/pathology , Malondialdehyde/metabolism , Organ Size/drug effects , Oxidative Stress/drug effects , Periodontitis/etiology , Periodontitis/metabolism , Rats , Rats, Wistar
20.
J Periodontol ; 90(9): 1023-1031, 2019 09.
Article in English | MEDLINE | ID: mdl-30801719

ABSTRACT

BACKGROUND: Periodontitis is an inflammatory disease that causes periodontium and hepatic alterations. Liver disease is related to the intake of foods rich in fat and sugars (high-fat). The objective of this study was to evaluate whether a high-fat diet can aggravate the liver disease caused by ligature-induced periodontitis in rats. METHODS: Twenty-one female rats were divided into three groups (n = 7 in each group): control; periodontitis (periodontitis induced with ligature) and high-fat + periodontitis (received hypercaloric diet and induction of periodontitis). The rats were submitted to the analyses of the following periodontal parameters: gingival bleeding index (GBI), probing pocket depth (PPD), tooth mobility (TM), and alveolar bone height. In the hepatic tissue, the levels of malondialdehyde (MDA), glutathione (GSH), total cholesterol, and myeloperoxidase activity (MPO) were measured. Liver samples were also histopathologically evaluated. Finally, blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, total cholesterol, cholesterol high-density lipoprotein (HDL), and uric acid were measured. RESULTS: The high-fat + periodontitis group presented an increase in the steatosis score (P < 0.05) for the histopathologic evaluation, when compared with the periodontitis group. MDA, uric acid and ALT levels also increased, whereas GSH and HDL levels showed lower values. CONCLUSION: A high-fat diet aggravates the liver disease caused by ligature-induced periodontitis in rats.


Subject(s)
Liver Diseases , Periodontitis , Alanine Transaminase , Animals , Aspartate Aminotransferases , Diet, High-Fat , Female , Rats , Rats, Wistar
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