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1.
Toxicol Mech Methods ; 34(5): 495-506, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38166540

RESUMO

The current study aimed to assess the antioxidant and antiproliferative effects of teucrium polium extract: computational and in vivo study in rats. Three groups of animals: Group (i) constitute the control group; Group (ii) HeLa group received an intrafemoral inoculation of HeLa cells and Group (iii) constitue the combination between HeLa + T. polium. The plant was administered by gavage. Our results revealed that HeLa cell injection showed an elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), creatinine, urea, calcium and phosphorus. The pretreatment with the plant extract reduced the level of these parameters. Injection of HeLa cells showed a significant decrease in phosphorus and calcium respectively. However, the pretreatment by T. polium modulated the level of these two minerals. Rats treated with HeLa cells line showed an increase in the level of lipid peroxidation as evaluated by the TBARS substances, at the same time, a significant decreases in SOD, CAT and GPx activities were noted in the HeLa group compared to the control. On the other hand, pretreatment with the plant improved the level of these enzymes. Our results revealed that T.polium has a therapeutic effect on some health problems. HeLa cell line induced a small infiltration in liver and kidney. T. polium reduced the damage in both liver and kidney, but did not reveal any proliferation of tumor cells from trabecular bone tissue. The computational study revealed that T. polium compound bound with high free binding energies and established promising network of molecular interactions with COX-2 and TNF-α macromolecules.


Assuntos
Antioxidantes , Proliferação de Células , Extratos Vegetais , Teucrium , Animais , Teucrium/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Células HeLa , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Masculino , Ratos Wistar , Ratos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Simulação de Acoplamento Molecular
2.
Cell Mol Biol (Noisy-le-grand) ; 69(1): 19-24, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-37213162

RESUMO

  Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease that causes acute inflammation in most body tissues. The current study aims to determine levels of some cytokines and chemokines in BALB/c mice with SLE and treatment by using BALB/c Mesenchymal stem cells (BM-MSCs). Forty BALB/c male mice were divided into four groups equally. The first and second groups received activated lymphocyte-derived DNA (ALD DNA) for induction of SLE. The second group received BM-MSCs/IV after the appearance of SLE clinical signs. The third group received BM-MSCs only, while the fourth group (control group) received PBS. All the study groups examine levels of IL-10, IL-6, TGFß1, VEGF, CCL-2, CCL-5/RANTES, IFNγ, and ICAM -1 by ELISA kits. The cytokines levels are determined in all the study groups. There was a significant increase in ANA and anti-dsDNA levels in the first group, while there was a decrease in the second group (treatment by BM-MSCs). There is no significant difference between the third and control groups in ANA and anti-dsDNA levels. The first group showed a significant increase in IL-6, CCL-5/RANTES, VEGF, ICAM, CCL-2, and IFNγ levels and a decrease in IL-10 and TGFß1. The second group showed low levels of IL-6, CCL-5/RANTES, VEGF, ICAM, CCL-2/MCP-1, and IFNγ but a high level of IL-10 and TGFß1 as compared with the control group. The third group has no significant differences from the control group in all the tested parameters. BM-MSCs have an essential therapeutic role in the functional regulation of cytokines and chemokines in mice with SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Células-Tronco Mesenquimais , Masculino , Animais , Camundongos , Interleucina-10 , Medula Óssea , Camundongos Endogâmicos BALB C , Interleucina-6 , Fator A de Crescimento do Endotélio Vascular , Citocinas , Lúpus Eritematoso Sistêmico/terapia , DNA
3.
Arch Environ Contam Toxicol ; 84(4): 484-503, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37119272

RESUMO

In this study, we focused on evaluating the responses of the cockle, Cerastoderma glaucum to in situ exposures to metals at three sites in the Gulf of Gabes in the coastal zone of Tunisia differing in levels of metal contamination. Firstly, we examined the general physiological state of the organisms. Secondly, we evaluated the bioaccumulation of several metals (Cd, Cu, Zn, Ni) in the cockles. Thirdly, we focused on evaluating histologically changes in gametogenesis and sexual maturity of the organisms. Finally, we determined the expression of seven key genes encoding enzymes or proteins involved in responses to different types of environmental stressors. Results showed a decrease in the general physiological status of the cockles, including a reduced condition index, sex ratios skewed to females (70% and 80% females in the intermediate and the contaminated site, respectively) and greater mortalities in tests under anoxic conditions (i.e., stress on stress test) in cockles collected from the most contaminated site (LT50 = 2.88 days) compared to the cockles from the intermediate site (LT50 = 5 days) and the less contaminated site (LT50 = 6 days). Results for metal bioaccumulation showed that the levels of Cd, Cu, Zn and Ni in cockles were consistent with the contaminant gradient, with the highest levels in cockles from the most contaminated site (1.04; 4.92; 52.76 and 13.81 µg/g dw, respectively), followed by those from the intermediate site (0.34; 2.94; 36.94; 17.40 µg/g dw, respectively) and then the less contaminated site (0.065; 1.27; 21.62 and 5.40 µg/g dw, respectively). Results from the gametogenesis and maturity index showed few differences in the reproductive cycle of cockles collected from the three study sites. There were different patterns of gene expression that were divided into three groups in terms of responses: (1) expression of genes involved in metal detoxification, ATP Binding Cassette Subfamily B Member 1 (ABCB1) and metallothionein MT) and genes for superoxide dismutases (i.e., Mn SOD and CuZn SOD), which did not show any difference in their levels of expression; (2) heat shock protein 70 (HSP70) gene expression, which decreased in cockles according to the pollution gradient, and (3) expression of catalase (CAT) and cytochrome oxidase subunit 1 (COI) genes was threefold and 1000-fold higher in cockles from intermediate and most contaminated sites compared to the less contaminated site. Therefore, changes in overall physiological condition, sex ratios and expression of HSP70, CAT and COI genes may be appropriate biomarkers for in situ studies of the impacts of metals in cockles. However, these biomarkers should be coupled to proteomics studies.


Assuntos
Cardiidae , Poluentes Químicos da Água , Animais , Feminino , Masculino , Cardiidae/genética , Cardiidae/metabolismo , Cádmio/análise , Poluentes Químicos da Água/análise , Metais/toxicidade , Monitoramento Ambiental/métodos , Biomarcadores/metabolismo , Metalotioneína
4.
Calcif Tissue Int ; 110(4): 475-488, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34988595

RESUMO

Breast cancer bone metastases (BCBM) result in serious skeletal morbidity. Although there have been important advances in cancer treatment methods such as surgery and chemotherapy, the complementary treatments, such as α-tocopherol acetate (ATA), still remain of key role via complementary and/or synergistic effects. The aim of this work was to study immune response in a rat model of BCBM due to Walker 256/B cells inoculation and the effect of ATA alone. Compared to the control group (CTRL), rat injected with Walker 256/B cells (5 × 104) in the medullar cavity (W256 group) showed osteolytic damages with marked tumor osteolysis of both cancellous and trabecular bone as assessed by X-ray radiology, micro-computed tomography, and histology. Rats inoculated with Walker 256/B cells and treated with ATA (45 mg/kg BW, W256ATA group) presented marked less tumor osteolysis, less disturbance of Tb.Th and Tb.Sp associated with conversion of rods into plates, and increased structure model index and trabecular pattern factor (Tb.Pf). Elsewhere, 3D frequency distributions of Tb.Th and Tb.Sp were highly disturbed in metastatic W256 rats. Overexpression of some genes commonly associated with cancer and metastatic proliferation: COX-2, TNF-α, and pro-inflammatory interleukins 1 and 6 was outlined. ATA alleviated most of the Walker 256/B cells-induced microarchitectural changes in the target parameters without turning back to normal levels. Likewise, it alleviates the BCSM-induced overexpression of COX-2, TNF-α, IL-1, and IL-6. In silico approach showed that ATA bound these proteins with high affinities, which satisfactory explain its beneficial effects. In conclusion, BCBM is associated with bone microarchitectural disorders and an immune response characterized by an overexpression of some key role genes in cancer proliferation and invasion. ATA exerted favorable effects on trabecular bone distribution and morphology, which may involve the COX-2, TNF-α, and ILs pathways.


Assuntos
Neoplasias da Mama , Osteólise , alfa-Tocoferol , Animais , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Ciclo-Oxigenase 2 , Suplementos Nutricionais , Osteólise/tratamento farmacológico , Osteólise/patologia , Ratos , Fator de Necrose Tumoral alfa , Microtomografia por Raio-X , alfa-Tocoferol/farmacologia
5.
Cell Mol Biol (Noisy-le-grand) ; 68(4): 113-121, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35988278

RESUMO

Sperm cryopreservation is a cost-effective means of preserving gene resources and transporting sperm across distant locations. However, due to the general disadvantages of using freeze-thawed sperm, to prevent this irreversible damage, cryopreservation techniques must be improved by the addition of additional cryoprotection agents. This study aims to improve the freezability of buck semen using an intratesticular injection of Autologous Platelet-Rich Plasma ( PRP) and confirm this theory by Casa laboratory analysis and gene expression detection of three genes (CATSPER1 , SPAG5 and Hsp70). Twenty rabbits a New Zealand healthy male were randomly divided into two equal groups; the control and PRP group which enriched with PRP, the semen collection was applied after 10 weeks, then each sample was divided into two fractions; First fractions we apply the laboratory semen analysis directly, and the second fractions were cryopreservation, then thawed after one month to apply the same laboratory analysis. The results of CASA, DNA fragmentation, and real time-PCR analysis had statistically significant differences (P<0.01) when compartment of these values after and before freezing, yet we don't record any statistical differences between the C group and CR group. This study's findings are extremely significant, indicating that intratesticular injection of PRP is a good method for using in enhancing the rabbit sperm procedure after freeze-thawing.


Assuntos
Plasma Rico em Plaquetas , Preservação do Sêmen , Animais , Criopreservação/métodos , Masculino , Coelhos , Sêmen , Preservação do Sêmen/métodos , Espermatozoides
6.
J Oncol Pharm Pract ; 28(5): 1031-1034, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34000920

RESUMO

INTRODUCTION: Functional variants of the Methylenetetrahydrofolate reductase (MTHFR) gene, the C677T and A1298C, have largely investigated in pharmacogenomics of Methotrexate (MTX) in acute lymphoblastic leukemia (ALL), yet the conclusions are inconsistent. In addition; most of these studies do not analyze haplotypes. Here, we investigate the MTHFR 677/1298 genotypes and the 677-1298 haplotype and characterize the MTX response in Northern African ALL patients. METHODS: Genomic DNA was extracted from whole venous from a total of 28 patients with ALL. Genotyping were carried out with restriction fragment length polymorphism (RFLP). A toxicity score (TS) is calculated for each patient and correlate to the haplotype. RESULTS: The allelic frequency of MTHFR 677T-1298C haplotype was 10.7% in ALL patients. According to the toxicity's score (TS) there was no significant differences between haplotype groups (p = 0.79): TS was higher with wild type of MTHFR (TS = 3.43; SEM ± 0.85) followed by combined genotype (677T-1298C) (TS = 2.67; SEM ± 0.88) and isolated variant (C677T or A1298C) (TS = 2.64; SEM ± 0.92). CONCLUSION: Despite the limitation of this study; our results suggest that the MTHFR 677T-1298C haplotype is common in ALL and may be a promising HD-MTX chemotherapy-related adverse effects biomarker.


Assuntos
Metotrexato , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metotrexato/efeitos adversos , Haplótipos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Genótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Polimorfismo de Nucleotídeo Único
7.
J Pediatr Hematol Oncol ; 43(6): e816-e818, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33060392

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL), a common blood cancer, is characterized by the interaction between genetic and environmental factors. Several variants of the Methylenetetrahydrofolate reductase (MTHFR), mainly the C677T (rs1801133), may affect susceptibility to ALL. AIM OF THE STUDY: The authors conducted this case-control study to evaluate the relationship between this variant of the MTHFR gene and the risk of ALL. MATERIALS AND METHODS: Forty-one patients with ALL and 35 non-ALL controls recruited in this study were genotyped utilizing polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The MTHFR 677CT genotype was significantly more frequently found in patients with ALL having a 2-fold increase in risk (P <0.01). CONCLUSION: Our results suggest that rs1801133 of MTHFR is a predictive risk marker to ALL in Tunisian ALL.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Dados Preliminares
8.
J Oncol Pharm Pract ; 27(6): 1382-1387, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32865163

RESUMO

BACKGROUND: Methotrexate (MTX) is a key drug in acute lymphoblastic leukemia (ALL) treatment; it inhibits DNA replication by blocking the conversion of 5, 10 Methylenetetrahydrofolate to 5-methylene tetrahydrofolate by methylenetetrahydrofolate reductase (MTHFR). Variants of the Methylenetetrahydrofolate reductase (MTHFR) and MTX related toxicities were largely investigated in several populations, nevertheless, the results are conflicting. OBJECTIVE: This study aimed to assess the prevalence of MTHFR SNVs: C677>T and A1298>C in Tunisian patients with ALL and the relation to the frequency of drug-induced complications. METHODS: 28 ALL patients were included in the study. They were treated according to EORTOC, in which a high dose of MTX (HDMTX) was prescribed. A toxicity score (ST) is calculated for each patient, summing the grades of toxicities. Genotyping of MTHFR variants was done with a PCR-based restriction fragment length polymorphism assay. RESULTS: The toxicity's score (TS) was higher with C677T variant compared to wild genotype (C677C) (TS = 4; IC95% [-2.65-13.32] versus TS = 2.5; IC95% [1.65-4.55], respectively; p = 0.2); but lower with the A1298C mutation compared to those with the wild genotype (A1298A) (TS = 2.5; IC95% [0.48-4.77], versus TS =3; IC95% [1.9-5.69], p = 0.4). HDMTX-related toxicity is associated with the 677CT genotype in ALL patients (RR = 1.41, p = 0.2); not for the A1298C [OR = 0.46, [0.08-2.61], p = 0.18]. CONCLUSION: Our preliminary findings highlight the impact of the C677T variant of MTHFR, but not the A1289C; in HD-MTX chemotherapy-related adverse effects in younger Tunisian ALL.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2) , Leucemia-Linfoma Linfoblástico de Células Precursoras , Genótipo , Humanos , Metotrexato/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
9.
Pestic Biochem Physiol ; 167: 104606, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32527427

RESUMO

We have investigated the effect of subchronic exposure to tetradifon (TDF), as an endocrine disruptor chemical, on some parameters related to serious metabolomic disorders such as obesity, type 2 diabetes and hyperlipidemia. TDF promoted significant increases in both duodenal and pancreatic α-amylase and lipase especially in the 12-weeks treated rats. Plasmatic glucose and lipid profile; total cholesterol (T-cholesterol), low density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c) and glyceride, were markedly disrupted. Compared with controls, biochemical liver injury parameters: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and lactate dehydrogenase (LDH) were significantly increased. Moreover, notable pathological features were reported in liver tissues. These results confirm a strong relationship between exposure to an endocrine disruptor and metabolic disorders. In fact, subchronic exposure to TDF lead to lipidemic and glycemic disruption associated hyperactivity in both α-amylase and lipase. Overall, these disruptions could be an important step on the pathway to metabolic pathology.


Assuntos
Diabetes Mellitus Tipo 2 , Disruptores Endócrinos , Animais , Hidrocarbonetos Clorados , Lipase , Fígado , Ratos , alfa-Amilases
10.
J Oncol Pharm Pract ; 25(5): 1182-1186, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30545275

RESUMO

CONTEXT: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, mainly the C677T, have been implicated as risk factors for several cancers as the acute lymphoblastic leukemia (ALL). In addition, a potential effect of such variant on the efficacy of methotrexate (MTX) has been reported. OBJECTIVE: In this study, we evaluated the impact of the C677T variant of MTHFR on MTX-related toxicity in ALL patients from Tunisia; to provide new insights for a personalized therapy based on the human genotype. MATERIALS AND METHODS: Genotyping was carried out with restriction fragment length polymorphism (RFLP) on blood samples from a total of 35 younger patients; suffering from ALL. RESULTS: In the ALL patients, the MTHFR 677CT genotype confers a greater risk of toxicity with 1.3 times as relative risk mainly the hepatic toxicity when compared with MTHFR 677CC. CONCLUSION: Our findings suggest that C677T polymorphism of MTHFR seems to be a good marker for MTX-related toxicity in ALL.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Masculino , Polimorfismo Genético , Adulto Jovem
11.
Andrologia ; 51(2): e13182, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30353557

RESUMO

The aim of this study was to investigate the protective effects of Teucrium polium (T. polium) on carbon tetrachloride (CCl4 )-induced male reproductive system damage. The effects of T. polium and vitamin C (Vit C) on sperm parameters, gonadotrophin and testosterone levels, oxidative status and testis tissue structure were assessed in CCl4 -treated male rats. CCl4 caused significant alteration of sperm parameters in epididymal and testicular tissues, a decrease in hormone levels, and a decrease in antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in testicular tissues. A noteworthy increase in malondialdehyde (MDA) level was induced in CCl4 -treated rats with some histopathological damages on the testes compared with control group. Remarkable ameliorations were observed with respect to all the previous parameters, following the administration of CCl4 with T. polium, and with vitamin C used as a positive control, when compared with CCl4 alone. Teucrium polium extracts showed good antioxidant performance, suggesting its protective effect against chemically induced reprotoxicity.


Assuntos
Antioxidantes/farmacologia , Tetracloreto de Carbono/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Testículo/efeitos dos fármacos , Teucrium , Animais , Catalase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testículo/patologia
12.
Toxicol Mech Methods ; 29(5): 313-321, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30676168

RESUMO

This work investigated the protective effects of Teucrium polium (T. polium) and vitamin C (Vit C) against carbon tetrachloride (CCl4) induced hepatotoxicity and nephrotoxicity in rats. T. polium reduced the Fer reduced antioxidant power (FRAP) (IC50 = 0.89 mg/ml) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 0.049 µg/ml) than Vit C, FRAP (IC50 = 0.71 mg/ml) and DPPH (IC50 = 0.029 µg/ml). Male albino Wistar rats were divided into six groups: Group I was used as controls, Group II received CCl4 in olive oil (0.5 ml/kg) by gavage, Group III received CCl4 in olive oil (0.5 ml/kg) by gavage after 3 d of receiving T. polium (5 g/l), orally, Group IV received T. polium (5 g/l) alone, by gavage, for 7 d, Group V received CCl4 in olive oil (0.5 ml/kg) by gavage after 3 d of receiving Vit C (250 mg/kg) by gavage and Group VI received Vit C (250 mg/kg) alone by gavage. CCl4 showed an increase of serum hepatic and renal markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. Moreover, we noted an increase of lipid peroxidations and a decrease in antioxidants enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) of CCl4 rats compared to controls. The pretreatment with (200 mg/kg) of T. polium and with Vit C (250 mg/kg) by gavage, for 7 d, displayed their ability to protect against oxidative damage and biochemical changes induced by CCl4. Our results were in accordance with histopathological observations.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Tetracloreto de Carbono/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Teucrium/química , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Rim/enzimologia , Rim/patologia , Fígado/enzimologia , Fígado/patologia , Extratos Vegetais/metabolismo , Ratos Wistar
13.
Mol Genet Genomics ; 293(2): 495-501, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29196848

RESUMO

In the era of the diseasomes and interactome networks, linking genetics with phenotypic traits in Turner syndrome should be studied thoroughly. As a part of this stratagem, mosaicism of both X and Y chromosome which is a common finding in TS and an evaluation of congenital heart diseases in the different situations of mosaic TS types, can be helpful in the identification of disturbed sex chromosomes, genes and signaling pathway actors. Here we report the case of a mosaic TS associated to four left-sided CHD, including BAV, COA, aortic aneurysms and dissections at an early age. The mosaicism included two cell lines, well-defined at the cytogenetic and molecular levels: a cell line which is monosomic for Xp and Xq genes (45,X) and another which is trisomic for pseudoautosomal genes that are present on the X and Y chromosomes and escape X inactivation: 45,X[8]/46,X,idic(Y)(pter→q11.2::q11.2→pter)[42]. This case generates two hypotheses about the contribution of genes linked to the sex chromosomes and the signaling pathways involving these genes, in left-sided heart diseases. The first hypothesis suggests the interaction between X chromosome and autosomal genes or loci of aortic development, possibly dose-dependent, and which could be in the framework of TGF-ß-SMAD signaling pathways. The second implies that left-sided congenital heart lesions involve sex chromosomes loci. The reduced dosage of X chromosome gene(s), escaping X inactivation during development, contributes to this type of CHD. Regarding our case, these X chromosome genes may have homologues at the Y chromosome, but the process of inactivation of the centromeres of the isodicentric Y spreads to the concerned Y chromosome genes. Therefore, this case emerges as an invitation to consider the mosaics of Turner syndrome and to study their phenotypes in correlation with their genotypes to discover the underlying developmental and genetic mechanisms, especially the ones related to sex chromosomes.


Assuntos
Cardiopatias Congênitas/genética , Mosaicismo , Aberrações dos Cromossomos Sexuais , Síndrome de Turner/genética , Adolescente , Coartação Aórtica/genética , Valva Aórtica/anormalidades , Valva Aórtica/metabolismo , Doença da Válvula Aórtica Bicúspide , Bandeamento Cromossômico , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Feminino , Cardiopatias Congênitas/complicações , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/metabolismo , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Síndrome de Turner/complicações
14.
Lipids Health Dis ; 17(1): 9, 2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29316974

RESUMO

BACKGROUND: Mentha piperita L. is a flowering plant belonging to the Lamiaceae family. Mentha plants constitute one of the main valuable sources of essential oil used in foods and for medicinal purposes. METHODS: The present study aimed to investigate the composition and in vitro antioxidant activity of Mentha piperita leaf essential oil (MpEO). A single dose of CCl4 was used to induce oxidative stress in rats, which was demonstrated by a significant rise of serum enzyme markers. MpEO was administrated for 7 consecutive days (5, 15, 40 mg/kg body weight) to Wistar rats prior to CCl4 treatment and the effects on serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ -glutamyl transpeptidase (γ-GT) levels, as well as the liver and kidney superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity and thiobarbituric acid reactive substances (TBARS) levels were evaluated. In addition, histopathological examinations of livers and kidneys was performed. RESULTS: The in vitro antioxidant activity of MpEO was lower than that of silymarin. Pretreatment of animals with MpEO at a dose of 5 mg/kg did not have a significant effect on ALT, AST, ALP, LDH, γGT, urea or creatinine levels in CCl4-induced stress. Whereas pretreatment with MpEO at doses of 15 and 40 mg/kg prior to CCl4, significantly reduced stress parameters (ALT, AST, ALP, LDH, γGT, urea and creatinine) compared to the CCl4-only group. Moreover, a significant reduction in hepatic and kidney lipid peroxidation (TBARS) and an increase in antioxidant enzymes SOD, CAT and GPx was also observed after treatment with MpEO (40 mg/kg) compared to CCl4-treated rats. Furthermore, pretreatment with MpEO at 40 mg/kg can also markedly ameliorate the histopathological hepatic and kidney lesions induced by administration of CCl4. CONCLUSIONS: We could demonstrate with this study that MpEO protects liver and kidney from CCl4-induced oxidative stress and thus substantiate the beneficial effects attributed traditionally to this plant.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Mentha piperita/química , Óleos Voláteis/farmacologia , Insuficiência Renal/prevenção & controle , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/sangue , Catalase/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Esquema de Medicação , Glutationa Peroxidase/metabolismo , Rim , L-Lactato Desidrogenase/sangue , Fígado , Masculino , Óleos Voláteis/isolamento & purificação , Estresse Oxidativo , Extratos Vegetais/química , Ratos , Ratos Wistar , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , gama-Glutamiltransferase/sangue
15.
J Clin Lab Anal ; 32(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28374953

RESUMO

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR; NM_005957.4) is the key enzyme for folate metabolism which plays in DNA biosynthesis and the epigenetic process of DNA methylation. MTHFR gene polymorphisms, the c. 677C>T and c. 1298A>C have been implicated as risk factors for several types of cancers as the acute leukemia. AIM: We have optimized a duplex polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) for the simultaneous detection of both variants in acute leukemia patients, from Tunisia. METHODS: Genomic DNA was extracted from EDTA-anticoagulant blood samples from a total of 50 patients suffering from acute leukemia (AL). After DNA extraction, the polymerase chain reaction using specific primers, designed using Primer 3 Software. Restriction Fragment Length Polymorphism (RFLP) was performed in two separate tubes followed by agarose gel electrophoresis. CONCLUSION: This new method has proved to be a rapid, simple, and reliable method that should facilitate high throughput genotyping of MTHFR polymorphisms in acute leukemia.


Assuntos
Técnicas de Genotipagem/métodos , Leucemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição/genética , Humanos
16.
J Assist Reprod Genet ; 34(8): 1067-1077, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28550386

RESUMO

PURPOSE: To study the role of Toll-like receptor 4 (TLR4) in human spermatozoa and to assess sperm parameters, oxidative stress markers, and acrosome reaction in response to the stimulation of TLR4 by its ligand, the lipopolysaccharide (LPS), as a major endotoxin of Gram-negative bacteria. METHODS: Our study was carried out in 73 sperm samples from patients undergoing semen analysis for couple infertility investigations. The studied patients were divided into three groups: normozoospermic fertile patients (n = 13), patients with abnormal and leukospermic semen (n = 13), and patients with abnormal and non-leukospermic semen (n = 47). TLR4 expression in human spermatozoa was initially analyzed by western blot. Sperm samples were incubated in the presence of LPS (200 ng/ml) for 18 h. Then, sperm motility and vitality were evaluated by microscopic observation and oxidative stress markers as malondialdehyde (MDA) and carbonyl groups (CG) were spectrophotometrically assessed in neat and selected sperm. A triple-stain technique was also performed to evaluate acrosome reaction in 15 sperm samples from infertile patients. RESULTS: TLR4 expression was confirmed in human spermatozoa with a molecular weight of 69 kDa. In the normozoospermic group, no significant differences in sperm parameters and oxidative stress markers were shown after incubation with LPS in neat and selected sperms. Regarding samples from the non-leukospermic group, LPS reduced spermatozoa motility and vitality rates in selected sperm (P = 0.003; P = 0.004, respectively). A significant increase of MDA and CG levels was also detected (P = 0.01; P = 0.02, respectively). However, only the MDA levels were significantly increased (P = 0.01) in neat LPS-stimulated sperm. The same results were shown within the leukospermic group. The comparison between the two groups, leukospermic and non-leukospermic, in selected sperms showed a more important LPS effect in the leukospermic group significantly on motility and MDA rates (P = 0.006; P = 0.009, respectively). Furthermore, a significant decrease in reacted spermatozoa rate was detected in response to LPS in selected sperm samples from infertile men (P = 0.03). CONCLUSIONS: These findings indicate that human spermatozoa express TLR4 and respond to LPS stimulation with alterations in viability, motility, and the acrosome reaction implicating reactive oxygen species (ROS) production in sperm samples from infertile patients.


Assuntos
Reação Acrossômica/efeitos dos fármacos , Infertilidade Masculina/metabolismo , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Receptor 4 Toll-Like/metabolismo , Adulto , Biomarcadores/metabolismo , Fertilidade/efeitos dos fármacos , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Sêmen/efeitos dos fármacos , Sêmen/metabolismo , Análise do Sêmen/métodos , Motilidade dos Espermatozoides/efeitos dos fármacos
17.
Pharm Biol ; 55(1): 775-781, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28084125

RESUMO

CONTEXT: Urtica urens L. (Urticaceae) is an important and commonly used plant for its medicinal and pharmacological properties. OBJECTIVE: We analyzed the antioxidant and antimicrobial activities of the leaves of Urtica urens in ethanol (EtOH) and water (WA) solvents, employing standard analytical methods. MATERIALS AND METHODS: Polyphenol, flavonoid and tannin content of Urtica urens leaves were determined, after their extraction, using EtOH (70%) and WA extracts as well as the antioxidant (DPPH, ABTS, ß-carotene and FRAP) and the antibacterial (via the method of dilution tests) activities of EtOH and WA extracts. RESULTS: The 70% EtOH of Urtica urens showed the highest values of total phenolic (31.41 mg GAE/g DW), flavonoids (6.81 mg quercetin/g DW), tannin (8.29 mg GAE/g DW) and TEAC (560 mmol Trolox/g DW), compared to the WA. The results of DPPH for EtOH (95.56%) were higher than that of WA (64.56%) at a concentration of 40 mg/L. The extracts displayed a FRAP 106.23 for EtOH and 30.55 µmol Fe(II)/g DW for WA. The results clearly indicated that EtOH was the strongest radical scavenger (IC50 = 245.65 ± 10.2 µg/mL). Ethanol was the most effective with minimum inhibitory concentration (MIC) < 250 µg/mL. WA has no antibacterial activity. DISCUSSION AND CONCLUSION: The results indicate that leaves of Urtica urens could be used as natural antioxidant and antimicrobial agents.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Urticaceae , Flavonoides/análise , Polifenóis/análise , Taninos/análise , Urticaceae/química
18.
Pharm Biol ; 55(1): 1407-1414, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27659955

RESUMO

CONTEXT: Since antiquity, Pistacia lentiscus L. (Anacardiaceae) fruit oil (PLFO) has been used as a remedy for primary health care such as burn treatment. OBJECTIVE: This study assesses the healing effect of PLFO on CO2 laser fractional burn in a rat model. MATERIALS AND METHODS: The study was carried out on 18 adult male Wistar rats. A second-degree laser burn (wound area = 2.2 cm2) was inflicted in the dorsal region by the application of CO2 fractional laser within the following parameters; Energy level: 25 MJ and Depth level: 4. After applying laser, the rats were divided into three groups: the first was treated with saline solution, the second with a reference cream 'CYTOL BASIC®' (0.13 µg/mm2) and the third with PLFO (0.52 µL/mm2). All treatments were topically administered for eight days. The healing effect was assessed using macroscopic, histological and biochemical parameters. RESULTS: After eight days, the higher percentage of wound healing contraction was observed among the PLFO-treated group (100%) followed by the 'CYTOL BASIC®' treated group (61.36%) and untreated group (32.27%). During the treatment, the PLFO-treated group showed less erythema, less crusting/scabbing, higher general wound appearance scores and a high content of collagen (220.67 ± 7.48 mg/g of tissue) than the other groups. DISCUSSION AND CONCLUSION: The current study has shown, for the first time, the healing effect of PLFO on CO2 laser fractional burn. Their wound healing effect could be attributed to their antimicrobial, anti-inflammatory and antioxidant effects.


Assuntos
Queimaduras/tratamento farmacológico , Fármacos Dermatológicos/farmacologia , Frutas/química , Lasers de Gás , Pistacia/química , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Queimaduras/etiologia , Queimaduras/metabolismo , Queimaduras/patologia , Colágeno/metabolismo , Fármacos Dermatológicos/isolamento & purificação , Modelos Animais de Doenças , Hidroxiprolina/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/isolamento & purificação , Óleos de Plantas/isolamento & purificação , Plantas Medicinais , Ratos Wistar , Pele/metabolismo , Pele/patologia , Fatores de Tempo
19.
J Surg Res ; 201(2): 464-72, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27020833

RESUMO

BACKGROUND: Despite the achievements in modern medicine, there is no effective natural treatment of second-degree burns till now. Therefore, the purpose of this study was to assess the wound-healing efficiency of three extracted oils, from the prickly pear, pumpkin and linseed on partial-thickness burns induced by fractional CO2 laser (an innovative up-to-date technique) in rats. MATERIALS AND METHODS: Thirty rats completing partial-thickness burns by fractional CO2 laser were randomly divided into five groups. The burns were measured, photographed, and topically treated daily with saline solution, "CYTOL BASIC," pumpkin-, linseed-, and prickly pear-extracted oils (0.52 µL/mm(2) of oil) until day 7. The response to treatments was assessed by macroscopic, histologic, and biochemical parameters. RESULTS: Due to their chemical composition, the extracted oils showed significant improvements over the control and reference groups during the trial for both general wound appearance and crusting. On day 7, the prickly pear, linseed, and pumpkin oils showed a significant decrease in the healing time (0 cm(2), 0.15 cm(2), and 0.18 cm(2), respectively) when compared to the control and reference groups (1.49 cm(2) and 0.85 cm(2)). Histologic assessment of the prickly pear oil-treated group revealed good healing proprieties compared with the other groups. The collagen content in prickly pear oil-treated group was found to be significantly greater (270.67 ± 7.48) than that in all other groups. CONCLUSIONS: Our experiment has shown, for the first time, a scientific evidence of the efficiency of extracted oils of prickly pear, pumpkin, and linseed on partial-thickness burns.


Assuntos
Queimaduras/tratamento farmacológico , Magnoliopsida , Fitoterapia , Óleos de Plantas/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Peso Corporal , Queimaduras/etiologia , Queimaduras/patologia , Colágeno/metabolismo , Cucurbita , Avaliação Pré-Clínica de Medicamentos , Linho , Lasers de Gás/efeitos adversos , Masculino , Opuntia , Óleos de Plantas/farmacologia , Distribuição Aleatória , Ratos Wistar , Pele/metabolismo , Pele/patologia
20.
Ecotoxicol Environ Saf ; 129: 164-70, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27039245

RESUMO

Air pollution is a threat for human health and wildlife. The aim of this study is to assess the pathophysiological changes and the oxidative-antioxidative status in testicular tissues of 40 Hybrid sparrows collected from four areas in Gabès city, one of the most polluted areas in Tunisia. The testis histopathological analysis revealed alterations in birds from Ghannouche, the polluted area. The thiobarbituric acid reactive substance (TBARS) levels were higher in testis of birds from the contaminated site compared to less polluted areas indicating oxidative damage to membrane lipids. Antioxidant enzyme activities (superoxide dismutase and catalase) were lower in testis sparrows from the polluted site compared with the reference site, suggesting deficiency of the antioxidant system to compensate for oxidative stress. Overall, our results suggest that the hybrid sparrow offers a suitable model for biomonitoring programs of atmosphere pollutants and the selected biomarkers could be useful tool to evaluate pollution impacts in living organisms.


Assuntos
Poluição Ambiental , Pardais/fisiologia , Testículo/metabolismo , Animais , Biomarcadores/metabolismo , Catalase/metabolismo , Cidades , Monitoramento Ambiental/métodos , Poluição Ambiental/efeitos adversos , Masculino , Estresse Oxidativo/fisiologia , Reprodução , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tunísia
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