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1.
J Biochem Mol Toxicol ; 38(1): e23560, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37860953

ABSTRACT

This study investigated the effect of N-acetylcysteine (NAC) and silymarin (SIL) in the liver of mice exposed to ethanol and lipopolysaccharides (LPS). Mice were divided into four groups (n = 6): naive, vehicle, NAC (200 mg/kg), and SIL (200 mg/kg). Treatments were given orally (po) once daily for 10 days. Liver injury was induced by administration of ethanol (30%, po) for 10 days, once daily, followed by a single administration of LPS (2 mg/kg, ip) 24 h before euthanasia. After the treatment period, animals were euthanized, and liver and blood samples were collected. NAC, but not SIL, prevented the increase in oxalacetic glutamic transaminase (OGT) and pyruvic glutamic transaminase (PGT) serum levels. NAC and SIL did not restore levels of reduced glutathione or hepatic malonaldehyde. The treatments with NAC or SIL showed no difference in the activity of glutathione S-transferase, superoxide dismutase, and catalase compared to vehicle group. Myeloperoxidase and N-acetylglucosaminidase activities are increased, as well as the IL-6 and IL-10 levels in the liver. The treatment with NAC, but not SIL, reduced the N-acetylglucosamines activity and the IL-6 and IL-10 amount in the liver. Histological findings revealed microsteatosis in the vehicle group, which was not prevented by SIL but was partially reduced in animals receiving NAC. Unlike other liver injury models, NAC (200 mg/kg) or SIL (200 mg/kg) did not positively affect antioxidant patterns in liver tissue of animals exposed to ethanol plus LPS, but NAC treatment displays anti-inflammatory properties in this model.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Silymarin , Mice , Animals , Acetylcysteine/pharmacology , Silymarin/pharmacology , Lipopolysaccharides/toxicity , Interleukin-10 , Ethanol/toxicity , Chemical and Drug Induced Liver Injury, Chronic/pathology , Interleukin-6/pharmacology , Liver/pathology , Antioxidants/pharmacology , Glutathione , Transaminases/pharmacology
2.
Immunol Invest ; 52(2): 154-161, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36394557

ABSTRACT

BACKGROUND: Dengue is a life-threatening disease. The factors that lead to severe cases are not completely understood. The host immune system is involved in the response to infections and plays an important role in dengue infection. IL-6 and iNOS are components of the immune system and genetic polymorphisms in these genes may be involved in dengue virus infection. The study aimed to investigate the association of genetic polymorphisms in the IL6 and iNOS genes and dengue. METHODS: We performed a case-control study using 60 dengue-infected individuals and 119 healthy controls. Polymorphisms in the IL6 (T15A) and iNOS (-1173CT) genes were amplified by Real-Time PCR. Statistical analyses were performed using BioEstat 5.0. RESULTS: We identified that the frequency of T/A genotype of IL6 was higher in dengue fever patients and C/T genotype of iNOS was higher in dengue hemorrhagic fever patients, however, no association was found between these polymorphisms and dengue. CONCLUSION: Polymorphisms in iNOS and IL6 were not associated with dengue infection.


Subject(s)
Dengue , Interleukin-6 , Humans , Interleukin-6/genetics , Dengue/genetics , Case-Control Studies , Nitric Oxide Synthase Type II/genetics , Polymorphism, Genetic
3.
J Ethnopharmacol ; 298: 115660, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35995277

ABSTRACT

ETHNOPHARMACOLOGICAL IMPORTANCE: Casearia sylvestris Sw. (Salicaceae) is a native plant from the Americas, where it is also known as "guaçatonga" or "erva-de-bugre." Although its leaves have been commonly used to treat inflammation and gastrointestinal disorders in South America, the antiulcer effects of an aqueous extract from this medicinal plant, similar to popular use, have not to be investigated yet. AIM OF THE STUDY: This study evaluated the hypothesis that the aqueous extract a of C. sylvestris (AEC) prevents the gastric ulcers and accelerates the healing of ulcers already installed, by assessing ultrasound imaging, histological and biochemical analyses. MATERIALS AND METHODS: Rats (females) were treated with AEC (3, 30 or 300 mg/kg) prior to the ethanol or piroxicam-induced gastric ulcers. The healing effect of AEC (300 mg/kg) was examined in 80% acetic acid-induced ulcer in rats, whereas the quality of healing was evaluated in recurrent 10% acetic acid-induced ulcer in mice with recurrence induced by interleukin 1ß. To assess the responses of the lesions, in addition to the classical methods used to analyze gastroprotection (ex vivo), we also measured the gastric wall thickness (in vivo) using ultrasonography. After euthanasia, the extent of ulcer was determined and the levels of reduced glutathione (GSH), lipid hydroperoxides (LOOH), nitrate, and the activities of myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase (NAG), superoxide dismutase (SOD), and glutathione S-transferase (GST) were measured. The antisecretory activity of AEC was also examined based on pylorus ligated rats. Furthermore, gastric tissue samples were analyzed histologically, and phytochemical analyses of the C. sylvestris extract were parallelly performed. RESULTS: The AEC (30 or 300 mg/kg) prevented ulcers in the ethanol- and piroxicam-induced acute. Moreover, the AEC at a dose of 300 mg/kg also accelerated the gastric healing of acetic acid-induced ulcer in rats by 48% and the ultrasonography records shown a decrease in the wall thickness and the extent of edema of ulcerous lesions promoted by the extract. The gastric healing effect of AEC was also accompanied by reduced MPO and NAG activities at acetic acid-induced ulcer in rats; as well as was by the reduction in the nitrate and LOOH levels, the increase in mucin and SOD activity, and by a partial recovery of GSH levels. The AEC (300 mg/kg) minimized the ulcer recurrence in mice exposed to IL-1ß, but the extract administration did not change pH or peptic activity of gastric juice in pylorus ligated rats. CONCLUSION: The results of this study provide convincing evidence for the therapeutic efficacy of C. sylvestris with respect to gastroprotection and indicate that ultrasound examination would be a potentially promising approach for evaluating gastroprotective effects in vivo. Collectively, our findings indicate that the gastric the gastroprotective and healing effects of aqueous extract C. sylvestris involve a reduction in acid secretion, promotion of the antioxidant system, reductions in the migration of neutrophils and mast cells, with a consequent lower inflammatory response, and the preservation of mucin.


Subject(s)
Anti-Ulcer Agents , Casearia , Stomach Ulcer , Acetic Acid/therapeutic use , Animals , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Ethanol/pharmacology , Female , Gastric Mucosa , Mice , Mucins , Nitrates , Phytotherapy , Piroxicam/adverse effects , Plant Extracts/adverse effects , Rats , Rats, Wistar , Rodentia , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/pathology , Superoxide Dismutase , Ulcer/drug therapy , Ultrasonography
4.
Neuroscience ; 498: 280-288, 2022 08 21.
Article in English | MEDLINE | ID: mdl-35716966

ABSTRACT

Cytokines and nitric oxide have been associated with impulsive and aggressive personality traits. We conducted the first study that investigated the role of SNPs in cytokines and nitric oxide genes and the influence in the progression of aggressive and impulsive behavior in 107 of cocaine and crack users. In this case-control, IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms were determined by Real-Time PCR. In addition, the relationship between these polymorphisms and Impulsivity and Aggression was determined. We found that the physical aggressiveness sub score was negatively correlated with the C allele of -819C/T polymorphism of the IL-10 (b = -0.14; p = 0.04). The T allele of the SNP -786T/C of the ENOS gene positively predicts traits of physical aggressiveness (b = 0.14; p = 0.04). The GA genotype (b = 0.22; p = 0.01) and the A allele (b = 0.15; p = 0.02) of -308 G/A polymorphism of the TNFA were positively correlated with aggressiveness physical. The GA genotype (b = 0.20; p = 0.03) was positively correlated with aggressiveness verbal. IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms might be associated with high risk of aggressive and impulsive behavior.


Subject(s)
Cocaine , Interleukin-10 , Aggression , Case-Control Studies , Cytokines , Genetic Predisposition to Disease , Genotype , Humans , Impulsive Behavior , Nitric Oxide , Nitric Oxide Synthase Type III , Personality , Polymorphism, Single Nucleotide
5.
Article in English | MEDLINE | ID: mdl-35295931

ABSTRACT

The hydroalcoholic extract of B. dracunculifolia (HEBD) and its major compound p-coumaric acid were evaluated against the severity of intestinal inflammation and behavioral changes like depressive and anxious behavior in colitis mice. Colitis was induced in Swiss mice by oral dextran sulfate sodium (DSS) administration for five days. The mice received vehicle (10 ml/kg), HEBD (3, 30, or 300 mg/kg), or p-coumaric acid (15 mg/kg) orally, once a day for twelve days. Behavioral tests were performed on the 11th and 12th days after the beginning of the treatments. Moreover, the colon, cortex, and hippocampus were collected to analyze oxidative and inflammatory parameters. The treatment with HEBD (300 mg/Kg), but not p-coumaric acid, showed decreased disease activity index (DAI) values compared to the vehicle group and partially preserved the villi architecture and mucin levels. Furthermore, the HEBD increased the antioxidant defenses in the colon and hippocampus and reduced the myeloperoxidase activity and IL-6 levels in the colon from colitis mice. Colitis mice treated with HEBD did not show depressive-like behavior in the tail suspension test. HEBD reduced colon inflammation, while it maintains antioxidant defenses and mucin levels in this tissue. It may reduce neuropsychiatric comorbidities associated with colitis through its antioxidant effects.

7.
Clin Pract Epidemiol Ment Health ; 18: e174501792201140, 2022.
Article in English | MEDLINE | ID: mdl-37274848

ABSTRACT

Background: Cocaine/crack use affects immune system molecules and development of mental disorders has been identified. Objective: To investigate the relationship of polymorphisms in the TNFA (-308G/A), IL-10 (-819C/T) and ENOS (-786T/C) genes with mental disorders in cocaine and crack users. Methods: A case-control study was carried out, which included 107 cocaine and crack users and 115 controls who never used healthy cocaine and crack. The SNPs in the TNFA (-308G/A), IL-10 (-819C/T) and ENOS (-786T/C) genes were genotyped by real time PCR. Results: As for the individuals included in this study, the average age of 31.4 years (± 8.59). We identified that the G/A genotype to TNFA (-308) (OR = 0.24; p = 0.03) and the A allele (OR = 0.30; p = 0.03) were associated with reduced risk for dysthymic disorder. The T allele of the IL-10 (-819) polymorphism was associated with decreased risk of developing panic disorder (OR = 0.44; p = 0.01), while the C allele was correlated with an increased risk for alcohol dependence (OR = 1.97; p = 0.04), alcohol abuse (OR = 1.81; p = 0.04) and psychotic syndrome (OR = 2.23; p = 0.01). C/C genotype was correlated with increased chances of developing current psychotic syndrome (OR = 4.23; p = 0.01). Conclusion: Our results suggest that genetic polymorphisms promote susceptibility or promote protection for clinical phenotypes of psychiatric comorbidities in cocaine and crack users and be considered as good prognostic markers.

8.
Recent Pat Biotechnol ; 15(3): 169-183, 2021.
Article in English | MEDLINE | ID: mdl-34353276

ABSTRACT

Extremophilic microorganisms from a wide variety of extreme natural environments have been researched, and many biotechnological applications have been carried out, due to their capacity to produce biomolecules resistant to extreme conditions, such as fibrinolytic proteases. The search for new fibrinolytic enzymes is important in the development of new therapies against cardiovascular diseases. This article aimed to evaluate the patents filed about protease with fibrinolytic activity produced by extremophilic microorganisms whose use is aimed at the development of new drugs for the treatment of cardiovascular diseases. The prospecting was carried out using data on deposits and patent concessions made available on the technological bases: European Patent Office (EPO), United States Patent and Trademark Office (USPTO), World Intellectual Property Organization (WIPO), Instituto Nacional de Propriedade Industrial - Brazil (INPI), The LENS and Patent Inspiration. The International Patent Classification and subclasses and groups for each document were also evaluated. Although 382 patents were selected using terms related to extreme environments, such as "thermophile" and "acidophiles", few were related to clinical use and were mainly performed using Bacillus subtilis and Streptomyces megasporus strains. A highlight of nattokinase was produced by Bacillus subtilis GDN and actinokinase by Streptomyces megasporus SD5. The low number of patents on enzymes with this profile (extreme environments) revealed a little-explored field, promising in the development of new microbial thrombolytic drugs, such as fibrinolytic enzymes with less adverse effects.


Subject(s)
Extremophiles , Biotechnology , Intellectual Property , Patents as Topic , Thrombolytic Therapy , United States
9.
Recent Pat Biotechnol ; 15(4): 250-265, 2021.
Article in English | MEDLINE | ID: mdl-34353277

ABSTRACT

BACKGROUND: L-asparaginase (L-ASNase, L-asparagine amidohydrolase, E.C.3.5.1.1) is an enzyme with wide therapeutic applicability. Currently, the commercialized L-ASNase comes from mesophilic organisms, presenting low specificity to the substrate and limitations regarding thermostability and active pH range. Such factors prevent the maximum performance of the enzyme in different applications. Therefore, extremophilic organisms may represent important candidates for obtaining amidohydrolases with particular characteristics desired by the biotechnological market. OBJECTIVES: The present study aims to carry out a technological prospecting of patents related to the L-asparaginases derived from extremophilic organisms, contributing to pave the way for further rational investigation and application of such enzymes. METHODS: This patent literature review used six patents databases: The LENS, WIPO, EPO, USPTO, Patent Inspiration, and INPI. RESULTS: It was analyzed 2860 patents, and 14 were selected according to combinations of descriptors and study criteria. Approximately 57.14% of the patents refer to enzymes obtained from archaea, especially from the speciesPyrococcus yayanosii (35.71% of the totality). CONCLUSION: The present prospective study has singular relevance since there are no recent patent reviews for L-asparaginases, especially produced by extremophilic microorganisms. Although such enzymes have well-defined applications, corroborated by the patents compiled in this review, the most recent studies allude to new uses, such as the treatment of infections. The characterization of the catalytic profiles allows us to infer that there are potential sources still unexplored. Hence, the search for new L-ASNases with different characteristics will continue to grow in the coming years and, possibly, ramifications of the technological routes will be witnessed.


Subject(s)
Asparaginase , Extremophiles , Asparagine , Biotechnology , Patents as Topic , Prospective Studies
10.
Infect Genet Evol ; 93: 104846, 2021 09.
Article in English | MEDLINE | ID: mdl-33933633

ABSTRACT

The Severe acute respiratory syndrome may be caused by coronavirus disease which has resulted in a global pandemic. Polymorphisms in the population play a role in susceptibility to severity. We aimed to perform a systematic review related to the effect of single nucleotide polymorphisms in the development of severe acute respiratory syndrome (SARS). Twenty-eight eligible articles published were identified in PubMed, ScienceDirect, Web of Science, PMC Central and Portal BVS and additional records, with 20 studies performed in China. Information on study characteristics, genetic polymorphisms, and comorbidities was extracted. Study quality was assessed by the STrengthening the REporting of Genetic Association (STREGA) guideline. Few studies investigated the presence of polymorphisms in HLA, ACE1, OAS-1, MxA, PKR, MBL, E-CR1, FcγRIIA, MBL2, L-SIGN (CLEC4M), IFNG, CD14, ICAM3, RANTES, IL-12 RB1, TNFA, CXCL10/IP-10, CD209 (DC-SIGN), AHSG, CYP4F3 and CCL2 with the susceptibility or protection to SARS-Cov. This review provides comprehensive evidence of the association between genetic polymorphisms and susceptibility or protection to severity SARS-CoV. The literature about coronavirus infection, susceptibility to severe acute respiratory syndrome (SARS) and genetic variations is scarce. Further studies are necessary to provide more concrete evidence, mainly related to Covid-19.


Subject(s)
COVID-19/genetics , Polymorphism, Genetic , Chemokines/genetics , Cytokines/genetics , Female , Genetic Association Studies , Genetic Markers , Genetic Predisposition to Disease , HLA Antigens/genetics , Humans , Male , Mannose-Binding Lectin/genetics
11.
Immunol Invest ; 50(1): 58-79, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32204641

ABSTRACT

Background: Chikungunya virus (CHIKV) is a global concern, inducing chikungunya fever and trigging an arthritogenic chronic phase beyond some severe forms. Outcomes of CHIKV infections in humans are dependent on genetic variations. Here, a systematic review was performed to show evidence of genetic variations on infection outcomes of patients. Methods: Searches were performed in Scopus, SciELO, MEDLINE/PubMed, Web of Science, OneFile (GALE), Periódicos CAPES and ScienceDirect Journals databases. The PICOS approach was used to assess the eligibility of records. A meta-analysis was also conducted to show an association between described alleles/genes and CHIKV infection outcome. Results: Reviews of genetic variants were conducted on genes: CD 209, OAS1, OAS2, OAS3, MIF, TLR-3, TLR-7, TLR-8, MYD-88, KIR, HLA-B; HLA-C; DRB1 and DQB1. Studies were performed on Gabon, Singapore, and India, including Indians, Malay, Gabonese and Chinese ethnicities and published between 2009-2017. The meta-analysis was performed with DRB1 *01; *03; *04; *07; *10; *11; *13; *14 and *15 and DQB1 *02; *03; *05 and *06 alleles with Indian population sample. Sampling power was >80% and a significant positive association between DRB1*14 and CHIKV infection was found (OR = 1.67, 95% CI = 1.04-2.67; p = .03). Conclusion: Majority of the studies were conducted in India. Meta-analysis suggests that DRB1*14 is related to the susceptibility of symptomatic CHIKV infection in Indian population. The literature about CHIKV infection and genetic variations is scarce. The precise role of genetic variation in CHIKV is not clear yet. Further studies are necessary to provide more concrete evidences.


Subject(s)
Chikungunya Fever/genetics , Chikungunya Fever/virology , Chikungunya virus/physiology , Host-Pathogen Interactions/genetics , Alleles , Chikungunya Fever/epidemiology , Disease Susceptibility , Genetic Predisposition to Disease , Histocompatibility Antigens Class II/genetics , Humans , Odds Ratio , Patient Outcome Assessment , Polymorphism, Genetic , Prognosis
12.
Immunol Invest ; 50(5): 492-526, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32602796

ABSTRACT

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools.Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case-control studies.Results: A total of 35 relevant case-control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA -308 G > A and IL-10 - 1082A>G) and ZNF263 (TNFA -238 G > A) transcription factors binding.Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.


Subject(s)
Alphapapillomavirus/physiology , Cytokines/genetics , Papillomavirus Infections/genetics , Precancerous Conditions/genetics , Squamous Intraepithelial Lesions of the Cervix/genetics , Uterine Cervical Neoplasms/genetics , Computational Biology , Female , Genetic Predisposition to Disease , Humans , Papillomavirus Infections/immunology , Polymorphism, Single Nucleotide , Risk , Squamous Intraepithelial Lesions of the Cervix/immunology , Uterine Cervical Neoplasms/immunology
13.
Chem Biol Interact ; 333: 109335, 2021 Jan 05.
Article in English | MEDLINE | ID: mdl-33245926

ABSTRACT

This study evaluated the gastric healing activity of eugenol, the main bioactive compound from clove (Syzygium aromaticun) essential oil. Five groups of female Wistar rats were submitted to acetic acid-induced ulcer model and treated with Vehicle (1 mL/kg, p.o.), eugenol (1, 10 or 100 mg/kg, p.o) or omeprazole (20 mg/kg, p.o), twice a day, by seven or fourteen days. Macroscopic, microscopic and biochemical analyses were performed in the ulcerated site. Eugenol (1 mg/kg, p.o) administered by 7 or 14 days accelerated the gastric healing process by 33% and 52%, respectively. The healing actions of eugenol were accompanied by the rescue on the histological architecture and the normalization of the superoxide dismutase and catalase activity. Moreover, eugenol (1 mg/kg, p.o) reduced the gastric mucosal myeloperoxidase activity and increased the mucin secretion. In contrast, eugenol at a dose of 100 mg/kg administered by 7 days enhanced 49% the ulcerated area, but at 10 mg/kg did not change the ulcer area after 7 or 14 days of treatment. Thus, despite the undesirable results due to the worsening of the gastric lesion with the use of eugenol in high doses, the antiulcer potential of this compound is evident and manageable in an adequate dose.


Subject(s)
Eugenol/adverse effects , Eugenol/pharmacology , Hormesis/drug effects , Stomach Ulcer/drug therapy , Animals , Catalase/metabolism , Chronic Disease , Eugenol/therapeutic use , Female , Glutathione/metabolism , Mice , Peroxidase/metabolism , Rats , Stomach Ulcer/metabolism , Stomach Ulcer/pathology , Superoxide Dismutase/metabolism
14.
Chem Biol Interact ; 327: 109166, 2020 Aug 25.
Article in English | MEDLINE | ID: mdl-32531310

ABSTRACT

Boldine is the main alkaloid of Peumus boldus Molina, widely used in the traditional medicine for the treatment of digestive disorders. It is a compound with excellent antioxidant and anti-inflammatory properties already described. Despite the widespread use of P. boldus for digestive disorders treatment, the gastroprotective effect of Boldine remains unknown. Considering the need for new approaches to treat gastric ulcers with fewer side effects than current therapy, this study aimed to investigate the gastroprotective effect of Boldine in mice, as well as the mechanisms underlying this effect. The gastroprotective effect of Boldine was evaluated on gastric ulcer induced by 60% ethanol/0.3 M HCl or indomethacin (100 mg/kg) in mice. Histological analysis and the mucin-like glycoprotein content were evaluated in ethanol-ulcerated tissue, as well as, oxidative stress and inflammatory parameters. The mechanisms involved in the effect of Boldine were evaluated by pretreating mice with NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), l-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p.). In addition, the in vitro effect of Boldine on H+/K+-ATPase activity was determined. Boldine was able to protect gastric mucosa against the damage induced by ethanol/HCl and indomethacin, as evidenced by reduced lesion area and histological analysis. Moreover, the alkaloid reduced oxidative stress and inflammatory mediators in ethanol-ulcerated tissue, beyond has increased mucin-like glycoprotein amount. Finally, Boldine effect is dependent on non-protein sulfhydryl groups and prostanoids but does not involve the inhibition of H+/K + -ATPase activity, being a promising natural resource for gastric ulcer treatment.


Subject(s)
Anti-Ulcer Agents/pharmacology , Aporphines/pharmacology , Gastric Mucosa/drug effects , Oxidative Stress/drug effects , Protective Agents/pharmacology , Stomach Ulcer/prevention & control , Animals , Ethanol , Female , Gastric Mucosa/pathology , H(+)-K(+)-Exchanging ATPase/metabolism , Indomethacin , Inflammation/chemically induced , Inflammation/prevention & control , Lipid Peroxidation/drug effects , Mice , Prostaglandins/metabolism , Rabbits , Stomach Ulcer/chemically induced , Sulfhydryl Compounds/metabolism
15.
Nutr Res ; 66: 95-106, 2019 06.
Article in English | MEDLINE | ID: mdl-30979660

ABSTRACT

Given the role of oxidative stress in ulcerative colitis (UC) etiology, and the amount of lutein (a carotenoid with antioxidant properties) in the dry hydroalcoholic extract of Tagetes erecta flowers (DHETE), this study investigated the intestinal anti-inflammatory properties of DHETE in an animal model of UC. The amount of lutein in the extract was determined by 1H-nuclear magnetic resonance spectroscopy, and total phenols, radical scavenger capability, cytotoxicity, and effects on reactive oxygen species and nitric oxide production were evaluated in vitro. Experimental UC was established by adding 5% dextran sulfate sodium (DSS) to drinking water, with the effects of DHETE (30-300 mg/kg, once a day for 7 days) on the morphological (colon length and weight), clinical (disease activity index and body weight loss), microscopic (histological score and mucin levels), and biochemical parameters analyzed. The lutein concentration found in DHETE was 8.2%, and DHETE scavenged 2,2-diphenyl-1-picrylhydrazyl radicals at 1000 µg/mL The exposure of intestinal epithelial cells to DHETE did not change its viability but reduced reactive oxygen species and nitric oxide production after lipopolysaccharide stimulation. In vivo, DHETE (300 mg/kg) attenuated weight loss, disease activity index, colon shortening, and histopathological changes promoted by DSS intake. Moreover, DHETE increased mucin colonic staining. The treatment with DHETE decreased myeloperoxidase activity as well as tumor necrosis factor and interleukin-6 levels. The extract also increased reduced glutathione levels and catalase activity and normalized superoxide dismutase and glutathione-S-transferase activities. In conclusion, DHETE reduced colitis severity by attenuating inflammatory cytokine secretion and improved the endogenous antioxidant defense in DSS-induced UC in mice.


Subject(s)
Colitis, Ulcerative/metabolism , Inflammation/prevention & control , Lutein/administration & dosage , Oxidative Stress/drug effects , Plant Extracts/administration & dosage , Tagetes/chemistry , Animals , Anti-Inflammatory Agents/administration & dosage , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Cytokines/metabolism , Dextran Sulfate , Disease Models, Animal , Ethanol , Flowers/chemistry , Inflammation/metabolism , Lutein/analysis , Male , Mice , Mucins/analysis , Water
16.
Acta Trop ; 190: 144-148, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30452889

ABSTRACT

Serotonin and nitric oxide seem to be involved in Dengue virus infection. The aim of this study was to investigate if SNPs in serotonin and nitric oxide are associated with dengue severity. A retrospective case-control study was conducted, with groups of dengue fever (DF; n = 78) and dengue hemorrhagic fever patients (DHF; n = 49). Genotyping was performed using qPCR and PCR. The power of the sample size was calculated by G*power software. The heterozygous SL for 5-HTTLPR SNP was significantly correlated with protection against progression to DHF in the codominant SS/SL/LL (OR = 0.22, 95% CI = 0.06-0.81, p = 0.011) and overdominant models SL vs SS + LL (OR = 0.19, 95% CI = 0.06-0.65, p = 0.003). For the ENOS (rs1799983) SNP, the genotype GT was positively associated with protection for development of the clinical form in DHF compared to dengue fever (OR = 0.39, 95% CI = (0.13-1.14), p = 0.0058) in codominant GG/GT/TT and overdominant model GT vs GG + TT (OR = 0.35, 95% CI = (0.12-1.02), p = 0.04). To our knowledge, this is the first study to identify the association of the serotonin and nitric oxide SNPs with dengue severity.


Subject(s)
Nitric Oxide Synthase Type III/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Severe Dengue/genetics , Adolescent , Adult , Alleles , Brazil , Case-Control Studies , Disease Progression , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Protective Factors , Retrospective Studies , Young Adult
17.
J Ethnopharmacol ; 226: 82-89, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30107246

ABSTRACT

ETHOPHARMACOLOGICAL RELEVANCE: The propolis is extensively used in folk medicine in natura or to prepare pharmaceutical formulations since ancient time to improve health or prevent diseases, among them gastrointestinal disorders. Aiming to contribute in the scientific validation about the popular use of Brazilian Green propolis (BGP) against gastritis and gastric ulcer, this work evaluated the antiulcer potential of isolated compounds from BGP, three prenylated p-coumaric acid derivatives and two flavonoids, respectively named: 3,5 diprenyl-4-hydroxycinnamic acid (artepillin C) (1), 3-prenyl-4-dihydroxycinnamoiloxy cinnamic acid (baccharin) (2), 3-prenyl-4-hydroxycinnamic acid (drupanin) (3), aromadendrin-4'-O-methyl-ether (4) and kaempferide (5). MATERIAL AND METHODS: The compounds were characterized by nuclear magnetic resonance and mass spectrometry. Their gastroprotective effects were evaluated against ethanol/HCl- and indomethacin-induced ulcer in mice. Further, histological, histochemical, oxidative and inflammatory parameters were analyzed at ulcerated tissue. Acid antisecretory activities also were also assessed. RESULTS: Compound 2 did not reduce the ethanol/HCl- induced ulcer at 30 mg/kg (p.o), whereas the minimum oral gastroprotective doses of 1, 3, 4 and 5 were 0.3, 0.3, 3 and 3 mg/kg, respectively. Besides, these compounds prevented ethanol/HCl-induced ulcer by intraperitoneal route, as well as indomethacin-induced ulcer by oral route. The gastroprotection was accompanied by normalization of superoxide dismutase, catalase and glutathione-S-transferase activities and reduction in myeloperoxidase activity. Moreover, the compounds 4 and 5 increased the gastric mucin content and 1 reduced TNF amount. Furthermore, 1, 3, 4 and 5 decreased volume, pH, total acidity and pepsin activity of the gastric juice from rats. CONCLUSIONS: Together, our findings showed a diversified mode of action elicited by 1, 3, 4 and 5 on the gastroprotection and contribute to explain the anti-ulcer activity reported for BGP.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Propolis/chemistry , Stomach Ulcer/drug therapy , Animals , Cinnamates/therapeutic use , Ethanol , Flavonoids/therapeutic use , Hydrochloric Acid , Indomethacin , Kaempferols/therapeutic use , Male , Mice , Phenylpropionates/therapeutic use , Propolis/therapeutic use , Stomach Ulcer/chemically induced
18.
Rev Bras Med Trab ; 15(4): 310-316, 2017.
Article in English | MEDLINE | ID: mdl-32377586

ABSTRACT

BACKGROUND: The study of the profile of medical records of tobacco growers contributes to discussions on the establishment of diagnosis and its causal correlation with work. OBJECTIVE: To investigate the profile of clinical information in medical records of tobacco growers. METHODS: The present was a descriptive field and documentary study, with quantitative approach, of 149medical records of farmers who visited basic health units in rural communities in the municipality of Arapiraca, Alagoas, Brazil, from 2008 to 2013. RESULTS: About 66% of the investigated population was female, with average age 58.6 years old (standard deviation ±16.4). The most significant clinical complaint found in the records was headache (16.71%), followed by low back pain (10.20%), dysuria or other urinary problems (8.90%) and stomachache (8.30%). Medical diagnoses included gastritis (15.1%), depression (7.1%), anxiety (7.1%), myalgia (7.1%) and arthritis/arthralgia (5.3%). Correlation between clinical complaints and work performed by tobacco growers was registered on one single medical record. CONCLUSION: The clinical profile of tobacco growers described in the medical records might be associated with their social and working conditions and related to pesticide and nicotine poisoning. However, the scarcity of information on the environmental and occupational risk context limits the establishment of a causal link. As a function of the relevance of the occupational-clinical conditions of this population of workers, improving medical records is necessary, as the temporal relationship between exposure and outcomes might account for the occurrence of the reported symptoms.


INTRODUÇÃO: O estudo do perfil dos registros clínicos em prontuários de fumicultores favorece a discussão do estabelecimento do diagnóstico e do nexo causal com o trabalho. OBJETIVO: Identificar o perfil dos registros clínicos em prontuários de fumicultores. MÉTODO: Trata-se de um estudo descritivo de campo e documental com abordagem quantitativa dos registros em 149 prontuários de fumicultores que frequentaram Unidades Básicas de Saúde da Família de comunidades rurais do município de Arapiraca, Alagoas, no período de 2008 a 2013. RESULTADOS: Foi identificado que 66% dos usuários são do sexo feminino, com média de idade de 58,6 anos (desvio padrão - DP±16,4). As queixas clínicas mais expressivas registradas nos prontuários estavam relacionadas à cefaleia (16,71%), seguida por dor lombar (10,20%), disúria ou outros problemas urinários (8,90%) e epigastralgia (8,30%). Quanto aos diagnósticos médicos, destacaram-se gastrite/epigastralgia (15,1%), depressão (7,1%), ansiedade (7,1%), mialgia (7,1%) e artrite/artralgia (5,3%). A correlação das queixas clínicas como trabalho desenvolvido pelos fumicultores foi registrada em apenas um prontuário. CONCLUSÃO: O perfil clínico dos fumicultores apresentado nos prontuários poderia estar associado às condições sociais e de trabalho e inter-relacionado com a intoxicação por agrotóxicos e nicotina. Porém, a escassez de registros contextualizando o ambiente e os riscos ocupacionais torna limitante o nexo causal. Pela relevância do quadro clínico-ocupacional desses trabalhadores, faz-se necessária a melhoria dos registros, o que poderia justificar os sintomas apresentados levando em consideração as relações temporais entre a exposição e o desfecho.

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