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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.
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Diabetes Mellitus Tipo 2 , Disruptores Endócrinos , Animais , Hidrocarbonetos Clorados , Lipase , Fígado , Ratos , alfa-AmilasesRESUMO
This study was designed to assess femur angioarchitecture and hematological effects of Walker 256/B cells in a rat model of tumor osteolysis. Tumor osteolysis was induced by in situ inoculation of Walker 256/B malignant cells. Six other rats were sham operated and served as control. Twenty days later, rats were euthanized, and femurs were collected than radiographed. Angioarchitecture [mean lumen diameter (MLD), wall thickness (WTh), Vessel number, volume, and separation (VNb, VV, and VSp respectively)] was studied by histomorphometry at 2 different positions (P1: diaphysis, and P2: metaphysis) of the operated femora. Some hematological parameters were also assessed. Walker 256/B induced marked tumor osteolysis, with cortical perforation and trabecular destruction, associated increase in bone vascularization (increases of VNb and VV and decrease of VSp). Angioarchitecture of W256/B rats was disorganized and showed large MLD and lower WTh. These effects were more prominent in P2. When compared to Sham group, significantly decreases at levels of red blood cell (RBC), hemoglobin (Hb), hematocrit (Ht), and white blood cell (WBC) were observed in W256/B rats. These results suggest that Walker 256/B cells induced tumor osteolysis, improve hypervasculature especially near the tumoral foci (P2) associated hematological disruption. Besides, tumor vessels showed abnormal (enlarged and thinner) and disorganized morphology.
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Carcinoma 256 de Walker/irrigação sanguínea , Fêmur/irrigação sanguínea , Osteólise/etiologia , Animais , Carcinoma 256 de Walker/sangue , Carcinoma 256 de Walker/diagnóstico por imagem , Carcinoma 256 de Walker/patologia , Modelos Animais de Doenças , Feminino , Fêmur/patologia , Hemoglobinas/análise , Humanos , Masculino , Radiografia , Ratos , Ratos Sprague-DawleyRESUMO
The cactus family plant has been used in folk medicine for a long time. In this work, Opuntia stricta chemical composition and its antioxidative and anti-inflammatory properties were investigated. Our results showed that O. stricta is highly rich in fibers and minerals. The present study assessed the levels of polyphenol contents and antioxidant and in vivo anti-inflammatory activities. The highest phenolic compounds and antioxidant activity were observed in the methanolic extract. Concerning the qualitative analysis, nine phenolic and organic acids were identified and quantified by high-performance liquid chromatography (HPLC). Luteolin-7-Glu (4.25 µg/g), apigenin-7-Glu (3.15 µg/g), and catechin (2.85 µg/g) were identified as major phenolic compounds. The predominant fatty acids detected by gas chromatography (GC) coupled to a flame ionization detector were linoleic and linolenic acids (35.11%). A factorial design plan was used to determine the effect of temperature, agitation speed, and maceration period on phenolic contents. In vivo, the methanol extract from Opuntia stricta showed anti-inflammatory activity. The computational modeling reveals that O. stricta compounds bind VEGF, IL-6, and TNF-α with high binding scores that reach -8.7 kcal/mol and establish significant molecular interactions with some key residues that satisfactorily explain both in vitro and in vivo findings. These data indicate that Opuntia stricta cladode powder could be potentially useful in pharmaceutical and food applications.
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This study investigated the druggability, pharmacokinetics and ethyl acetate extract of Teucrium polium (EA T. polium) and the protective effect against carbon tetrachloride (CCl4) induced liver cirrhosis in rats. The total antioxidant capacity (TAC) and scavenging activity of the extract were examined. The in vivo protective study was based on the use of an animal model of CCl4-induced liver cirrhosis. Four groups of rats have been used: Group I: control rats; Group II: received CCl4 in olive oil (0.5 mL/kg); Group III: received the EA T. polium (25 mg/kg) of pretreatment for seven days by gavage then CCl4 in olive oil by gavage for 15 days. Group IV: received the EA of T. polium for seven days (25 mg/kg). EA T. polium was found to possess significant antioxidant capacity. CCl4 caused a hepatotoxicity associated increase in both levels of AST and ALT, which were reduced back to normal values following EA T. polium pretreatment. Hepatotoxicity associated structural modifications of liver tissues and increase in thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and carbonyl proteins (CP), associated decreases in several assessed antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The in vivo findings on the protective effect of T. polium were supported by its druggability, its pharmacokinetic properties and molecular docking assays. These results confirm the modulatory antioxidant and hepatoprotective potential of T. polium in this experimental liver cirrhosis model. T. polium phytochemicals are good candidates for further pharmaceutical explorations and drug design.
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Fighting against the emergent coronavirus disease (COVID-19) remains a big challenge at the front of the world communities. Recent research has outlined the potential of various medicinal herbs to counteract the infection. This study aimed to evaluate the interaction of artemisinin, a sesquiterpene lactone extracted from the Artemisia genus, and its derivatives with the SARS-CoV-2 main protease. To assess their potential use against COVID-19, the interactions of the main active principle of Artemisia with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) was investigated through in silico probing. Our results showed that artemesinin and its derivatives manifested good oral absorption and bioavailability scores (0.55). They potently bound to the Mpro site of action-specifically, to its Cys145 residue. The selected compounds established two to three conventional hydrogen bonds with binding affinities ranging between -5.2 and -8.1 kcal/mol. Furthermore, artemisinin interactions with angiotensin converting enzyme 2 (ACE2) were dependent on the ACE2 allelic variants. The best score was recorded with rs961360700. A molecular dynamic simulation showed sufficient stability of the artemisinin-Mpro complex on the trajectory of 100 ns simulation frame. These binding interactions, together with drug-likeness and pharmacokinetic findings, confirmed that artemisinin might inhibit Mpro activity and explain the ethnopharmacological use of the herb and its possible antiviral activity against SARS-CoV-2 infection inducing COVID-19. Nevertheless, it interacted differently with the various ACE2 allelic variants reported to bind with the SARS-CoV-2 spike protein.
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Diabetes mellitus has become a serious problem associated with health complications, such as metabolism disorders and liver-kidney dysfunction. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study was conducted to evaluate the hypoglycemic, antilipidemic, and antioxidant effects of EGCG in surviving diabetic mice. Alloxan diabetic mice were treated with EGCG. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglycerides, urea, creatinine, and transaminases. Their livers and kidneys were isolated to assess oxidative damage and to perform histological analysis. Both EGCG and insulin treatment of diabetic mice resulted in a significant reduction in fasting blood glucose levels. EGCG supplementation also ameliorated hepatic as well as renal toxicity indices. Moreover, diabetic mice injected with EGCG exhibited significant changes in antioxidant enzyme activities in the liver and kidney. Histological analyses also showed that it exerted an ameliorative action on these organs and efficiently protected the liver-kidney functions of diabetic mice. EGCG was found to bind α-amylase, PTP1B, and α-glucosidase with good affinities ranging from -6.1 to -8.4 kcal/mol. The findings revealed that EGCG administration induced attractive curative effects on diabetic mice, particularly in terms of liver-kidney function. EGCG can, therefore, be considered as a potential strong candidate for future applications to treat and alleviate diabetic burden. Its pharmacokinetics, high affinities, and molecular interactions with the targeted receptors satisfactory explain the in vivo findings.
Assuntos
Catequina , Diabetes Mellitus Experimental , Hiperglicemia , Hiperlipidemias , Animais , Camundongos , Aloxano/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Glicemia/metabolismo , Hiperlipidemias/tratamento farmacológico , Catequina/farmacologia , Catequina/uso terapêutico , Estresse Oxidativo , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Fígado , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismoRESUMO
In the present study we focused on the anti-asthmatic and antioxidant effects of Zingiber officinalis roscoe L. (ZO) aqueous extract. This study includes 20 adult male rats, which were grouped into four; Group I: control group; Group II: asthmatic group (Ovalbumin sensitized/challenge model, Oval group); Group III: received ovalbumin sensitized/challenge associated a dose of 207 mg/kg body weight (BW) of ZO (Oval + D1 group); Group IV: received ovalbumin sensitized/challenge associated a dose of 414 mg/k BW of ZO (Oval + D2 group). After 21 days, blood and lung samples were collected for biochemical, hematological, and histopathological analyses. The ameliorative effect of ZO phytochemical compounds was also assessed by in silico approach on transducer and activator of transcription 6 (STAT6) and tumor necrosis factor-α (TNF-α) receptors. The oxidative/antioxidative status was evaluated in the lung tissues. Our results show that ZO extract alleviated the ovalbumin-induced hematological and biochemical disruptions associated oxidative injury. In fact, white and red blood cells (WBC and RBC, respectively), aspartate aminotransaminase (ASAT), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) were significantly disrupted (p < 0.05) in Oval group and alleviated following ZO treatment. Besides, several histopathological features were outlined in lung tissues of Oval group. Interestingly, ZO was found to exert ameliorative effects on tissue level. In silico analyses, particularly the binding affinities, the number of H-bonds, the embedding distance and the molecular interactions of ZO phytochemical compounds with either STAT6 or TNF-α supported the in vivo results. These findings confirm the potential ethno-pharmacological effects of ZO against asthma and its associated complications.
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We have investigated whether exposure to tetradifon causes ovary injuries, disrupts folliculogenesis in rat and whether ovary hormones (estrogen and progesterone) to be affected by this endocrine-active agent. Female rats were exposed orally to a dose of 28.9 mg/kg/day for 6 or 12 weeks. After sacrifice, ovary glands were examined for morphometric changes. The serums were used to determine levels of 17beta-estradiol and progesterone. Results showed no sign of toxicity. However, tetradifon promoted a significant increase in the percentage of atretic follicles in the 12-weeks treated rats. Number and the diameter of mature follicles (tertiary and preovulatory) were markedly diminished together with a reduction of the relative weight of ovaries. Compared with controls, the treated rats exhibited significant reduction in serum 17beta-estradiol and progesterone levels. These results suggest an endocrine disruption by tetradifon which may interfere with ovarian follicles development in rat.
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Disruptores Endócrinos/toxicidade , Hidrocarbonetos Clorados/toxicidade , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Animais , Comportamento Animal/efeitos dos fármacos , Disruptores Endócrinos/administração & dosagem , Estradiol/sangue , Ciclo Estral/efeitos dos fármacos , Feminino , Atresia Folicular/efeitos dos fármacos , Hidrocarbonetos Clorados/administração & dosagem , Tamanho do Órgão/efeitos dos fármacos , Folículo Ovariano/anatomia & histologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Progesterona/sangue , RatosRESUMO
Myrtus communis L. (Myrtle) is one of the most important aromatic and medicinal species from the Myrtaceae family. It is traditionally used as antiseptic, disinfectant drug and hypoglycemic agent. The aim of our study was to evaluate the protective effect of Myrtus communis essential oil (McEO) on CCl4-induced hepatotoxicity in rat. Thirty two adult Wistar rats were divided into 4 groups of 8 each: (1) a control group; (2) was given a single dose of CCl4 (1 mL kg-1 in 1% olive oil. ip) on the 14th day (3) were given during 15 days a daily i.p. injection of McEO at 250 mL kg-1 b.w (4) a group was pretreated with McEO and intoxicated with CCl4 on the 14th day. The major components of McEO are α-pinene (35.20%), 1,8-cineole (17%), linalool (6.17%) and limonene (8.94%) which accounted for 67.31% of the whole oil. The antioxidant activity of McEO was evaluated using DPPH scavenging ability, ß-carotene bleaching inhibition and hydroxyl radical-scavenging activity. Moreover, the effect of McEO (250 mg kg-1 body weight BW) administrated for 14 consecutive days was evaluated in wistar rat. Administration of a single dose of CCl4 caused hepatotoxicity as monitored by an increase in lipid peroxidation (thiobarbituric acid reactive substances) as well in protein carbonyl level but decreased in antioxidant markers in the liver tissue. The McEO pre-treatment significantly prevented the increased plasma levels of hepatic markers and lipid levels induced by CCl4 in rats. Furthermore, this fraction improved biochemical and histological parameters as compared to CCl4-treated group. Our results suggest that M. communis contains promising substances to counteract the CCl4 intoxication and which may be efficient in the prevention of hepatotoxicity complications.
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Scorpion envenoming is less studied in pregnant victims. In this work, the effect of Buthus occitanus tunetanus on parturition in late pregnancy was studied in an animal model. Four groups of six primigravid female rats, each one at the 22nd day of pregnancy, were used. The first two groups had received an intra-peritoneal injection of 500 microg/kg of Buthus occitanus tunetanus crude venom or a physiological saline solution and left until foetal delivery. Then, the time elapsed until the first pup delivery and that separating the first and latest ones were measured. The other two groups served for the uterine electrophysiological activity exploration. Rats were anaesthetized, artificially ventilated and had received an intraperitoneal injection of 500 microg/kg of Buthus occitanus tunetanus crude venom or a physiological saline solution. Our results showed a significant increase of the latency to foetal delivery, labour time, and uterine contractile activity in envenomed rats compared to controls. Such signs are usually seen in dynamic dystocia. It was concluded that Buthus occitanus tunetanus envenoming might induce a dynamic dystocia, when it occurred in late pregnancy.
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Venenos de Escorpião/toxicidade , Animais , Animais Recém-Nascidos , Coito , Feminino , Masculino , Parto/efeitos dos fármacos , Gravidez , Prenhez/efeitos dos fármacos , Ratos , Ratos Wistar , EspermatozoidesRESUMO
Abstract Huge plethora of studies pointed out the importance of several Artemisia herb molecules as treatment for many diseases. Among these natural substances, some molecules are known to counteract fever, inflammation, blood clotting and oxidative stress. Furthermore, they are dotted with activities against different strains of viruses including the SARS-coronaviruses. For these beneficial properties, these medicinal herbs are deemed as a potential candidate for covid-19 pandemic.
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We examined the effects of vitamin E supplementation (VES) on osteoclast (OC) resorbing activity and cytomorphometry in Walker 256/B tumor osteolytic rats. Twenty-four aged male rats were randomized into 3 groups: 6 were sham operated; 9 were injected in the right hind limb with Walker 256/B cells (W256 group); and 9 were injected as above and supplemented with VE (45mg/kg BW) (W256VE group). Twenty days later, bone mass (BV/TV) and some microarchitectural parameters were assessed. Some histodynamic parameters, cellular and nuclear form factors (FFC and FFN), and nuclear-cytoplasmic ratio (N/C) of OC were measured for each group. W256 group exhibited osteolytic lesions in the operated femora. Walker 256/B induced trabecular perforation and decreased BV/TV associated with significant increases in OC numbering (N.Oc/B.Ar and Oc.N/B.Pm) and activity (ES/BS and Oc.S/BS). While FFN remain unchanged, the FFC and N/C ratio increased in the W256 group. W256VE showed less osteolytic lesions. Moreover, disruption of bone microarchitecture and OC activity in W256VE group decreased. VES reduced the malignant Walker 256/B-induced enhanced OC resorbing activity with cytoinhibition rate reaching 41%. The protective effect of VE may be due to its modulation of OC cytomorphometry and subsequently their activity.
Assuntos
Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama Masculina/tratamento farmacológico , Suplementos Nutricionais , Fêmur/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteólise/prevenção & controle , Vitaminas/farmacologia , alfa-Tocoferol/farmacologia , Fosfatase Ácida/metabolismo , Animais , Biomarcadores/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/secundário , Neoplasias da Mama Masculina/complicações , Neoplasias da Mama Masculina/patologia , Fêmur/metabolismo , Fêmur/patologia , Isoenzimas/metabolismo , Masculino , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteólise/etiologia , Osteólise/metabolismo , Osteólise/patologia , Ratos , Ratos Sprague-Dawley , Fosfatase Ácida Resistente a Tartarato , Fatores de TempoAssuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ácido Mefenâmico/efeitos adversos , Extratos Vegetais/efeitos adversos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Pré-Escolar , Humanos , Masculino , Ácido Mefenâmico/administração & dosagem , Extratos Vegetais/administração & dosagem , Plantas Medicinais/químicaRESUMO
BACKGROUND: Defining cancer stem cells and their origins is of much controversy,and constitutes a challenged knockout for cell targeting- anticancer drugs. Herein,we put forward a hypothetic model for cancer stem cells initiation from bone marrow stem cells. These later, will differentiate into an ancestral progenitor that activates a memorial program - the black box cassette- that is responsible of abnormal neo-organogenesis in the form of tumors and metastases. To approve this model, we assume that characterizing and investigating the most primitive forms of the bone marrow progenitors is required; both inside their niche and in circulation of cancer patients.
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The effects of subchronic exposure to tetradifon on biochemical related kidney toxicological parameters [creatinine (CRT), urea, and uric acid (UA)] were examined. Oxidative stress in kidney tissue was also assessed by measuring vitamin C (VitC) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)]. Tetradifon was administered orally to 12 rats at a cumulative dose of 24.3 mg/kg for 12 weeks. Twelve additional rats, no treated, have served as control. Control and treated animals were sacrificed after 6 or 12 weeks. For each group, kidneys were examined for morphometric changes. Results showed that tetradifon induced significant increases in CRT and urea, and decrease in UA. Morphometrically, while mean glomerular volume decreased percentage of sclerosed glomeruli increased in treated rats. Index of interstitial fibrosis was significantly higher. Moreover, renal antioxidant enzyme (SOD and GPx) activities and VitC content decreased. We concluded that tetradifon possessed nephrotoxic by promoting kidney morphometric and functional damage and depleting renal antioxidant defense system in rats.
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Hidrocarbonetos Clorados/toxicidade , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Feminino , Rim/metabolismo , Rim/patologia , Ratos , Ratos WistarRESUMO
Scorpion envenoming is less studied during gestation; however, it may induce various biological disturbances in maternal organism and hypothetical ones on their fetuses. The scope of this report was to elucidate some biological effects of such poisoning in late pregnant rats. Hence, TBARS levels in maternal lung, placental and fetal pulmonary and hepatic tissues and dam's biochemical blood parameters (glucose, creatinine, 17-beta estradiol, progesterone, blood nitrogen urea, sodium and potassium maternal plasma concentrations) had been evaluated after saline (G1), and scorpion venom (G2: 30 min and G3: 60 min) injections in 22nd day pregnant rats. Histological microscopic examination of these tissues was also carried out in HE-stained paraffin sections. In addition, the mean arterial blood pressure following the envenomation variations was measured in three rats from the same pool. Our results showed that Buthus occitanus tunetanus crude venom induced significant increase in maternal, placental and fetal tissues lipid peroxidation, concomitant with blood pressure elevation. Maternal plasma creatinine, estradiol and progesterone concentrations levelled up significantly after 30 min or later (60 min) after the venom injection. Except for a probable pronounced oedema and few congestions in maternal lungs and degenerative aspects of trophoblast cells, all examined tissues showed a conserved structure. These results suggest that scorpion envenomation may induce gestation process disturbances and threatens both mother's and fetus' well-being.