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1.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 282-288, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496160

RESUMO

OBJECTIVE: To determine the effect of trimetazidine on cardiac function and exercise tolerance in primary hypertension patients with type 2 diabetic. METHODS: In this randomized, double-blind, placebo-controlled prospective study, 60 primary hypertensive patients with diabetic were equally assigned into two groups, patients received trimetazidine (20 mg, 3 times a day) or placebo for 1 year. Echocardiography, cardiopulmonary exercise testing were performed; and the plasma N terminal pro B type natriuretic peptide (NT-ProBNP), hr-CRP, TNF-α, angiotensin Ⅱ and endothelin concentration were determined before and after treatment. RESULTS: In trimetazidine group, the left ventricular mass index, the mitral flow velocity E wave to A wave ratio (E/A), the peak early diastolic velocity (VE) to late diastolic velocity (VA) ratio (VE/VA) and the peak systolic velocity (Vs) were significantly improved, the plasma NT-ProBNP level was significantly decreased, and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were significantly increased (all P<0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all P<0.05) and with placebo (all P<0.05). There were no significant differences in any of above parameters after treatment in placebo group (all P>0.05). No severe adverse reaction was observed in both groups. CONCLUSIONS: For patients with both hypertension and diabetes, trimetazidine can improve cardiac function and increase exercise tolerance.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Tolerância ao Exercício , Coração , Hipertensão , Trimetazidina , Complicações do Diabetes/complicações , Diabetes Mellitus/tratamento farmacológico , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Coração/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Resultado do Tratamento , Trimetazidina/farmacologia , Trimetazidina/uso terapêutico , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico
2.
J Environ Sci (China) ; 85: 1-8, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31471016

RESUMO

Metalaxyl is an anilide pesticide that is widely used to control plant diseases caused by Peronosporales species. In order to study the toxic effects, zebrafish embryos were exposed to metalaxyl at nominal concentrations of 5, 50 and 500 ng/L for 72 hr, and the cardiac development and functioning of larvae were observed. The results showed that metalaxyl exposure resulted in increased rates of pericardial edema, heart hemorrhage and cardiac malformation. The distance between the sinus venosus and bulbus arteriosus, stroke volume, cardiac output and heart rate were significantly increased in larvae exposed to 50 and 500 ng/L metalaxyl compared to solvent control larvae. Significant upregulation in the transcription of tbx5, gata4 and myh6 was observed in the 50 and 500 ng/L treatments, and that of nkx2.5 and myl7 was observed in the 5, 50 and 500 ng/L groups. These disturbances may be related to cardiac developmental and functional defects in the larvae. The activity of Na+/K+-ATPase and Ca2+-ATPase was significantly increased in zebrafish embryos exposed to 500 ng/L metalaxyl, and the mRNA levels of genes related to ATPase (atp2a11, atp1b2b, and atp1a3b) (in the 50 and 500 ng/L groups) and calcium channels (cacna1ab) (in the 500 ng/L group) were significantly downregulated; these changes might be associated with heart arrhythmia and functional failure.


Assuntos
Alanina/análogos & derivados , Coração/crescimento & desenvolvimento , Poluentes Químicos da Água/toxicidade , Alanina/toxicidade , Animais , Embrião não Mamífero , Coração/efeitos dos fármacos , Peixe-Zebra/embriologia
4.
Dokl Biochem Biophys ; 486(1): 171-174, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367814

RESUMO

Under conditions of the experimental model of Parkinson's disease at the preclinical (early) and clinical stage-injection of mice with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 5 and 10 weeks-the toxic effects of MPTP was evaluated (the content of catecholamines and their metabolites in the heart, which receives the most extensive sympathetic innervation, was determined). The obtained data indicated the beginning of desympathization of the heart at the preclinical stage of PD and its progression at the clinical stage of the disease.


Assuntos
Catecolaminas/metabolismo , Neurotoxinas/toxicidade , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologia , Animais , Coração/efeitos dos fármacos , Coração/inervação , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Adv Exp Med Biol ; 1193: 1-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31368095

RESUMO

Several review articles have been published on the neurobehavioral actions of acetaldehyde and other ethanol metabolites as well as in major alcohol-related disorders such as cancer and liver and lung disease. However, very few reviews dealt with the role of alcohol metabolism in the adverse cardiac and autonomic effects of alcohol and their potential underlying mechanisms, particularly in vulnerable populations. In this chapter, following a brief overview of the dose-related favorable and adverse cardiovascular effects of alcohol, we discuss the role of ethanol metabolism in its adverse effects in the brainstem and heart. Notably, current knowledge dismisses a major role for acetaldehyde in the adverse autonomic and cardiac effects of alcohol because of its low tissue level in vivo. Contrary to these findings in men and male rodents, women and hypertensive individuals are more sensitive to the adverse cardiac effects of similar amounts of alcohol. To understand this discrepancy, we discuss the autonomic and cardiac effects of alcohol and its metabolite acetaldehyde in a model of hypertension, the spontaneously hypertensive rat (SHR) and female rats. We present evidence that enhanced catalase activity, which contributes to cardioprotection in hypertension (compensatory) and in the presence of estrogen (inherent), becomes detrimental due to catalase catalysis of alcohol metabolism to acetaldehyde. Noteworthy, studies in SHRs and in estrogen deprived or replete normotensive rats implicate acetaldehyde in triggering oxidative stress in autonomic nuclei and the heart via (i) the Akt/extracellular signal-regulated kinases (ERK)/nitric oxide synthase (NOS) cascade and (ii) estrogen receptor-alpha (ERα) mediation of the higher catalase activity, which generates higher ethanol-derived acetaldehyde in female heart. The latter is supported by the ability of ERα blockade or catalase inhibition to attenuate alcohol-evoked myocardial oxidative stress and dysfunction. More mechanistic studies are needed to further understand the mechanisms of this public health problem.


Assuntos
Acetaldeído/farmacologia , Fármacos do Sistema Nervoso Autônomo/farmacologia , Etanol/metabolismo , Coração/efeitos dos fármacos , Animais , Feminino , Masculino , Miocárdio , Estresse Oxidativo , Ratos , Ratos Endogâmicos SHR
6.
Environ Res ; 177: 108661, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442789

RESUMO

BACKGROUND: Ethanol vehicles release exhaust gases that contribute to the formation of secondary organic aerosols (SOA). OBJECTIVE: To determine in vivo toxicity resulting from exposure to SOA derived from vehicles using different ethanol-gasoline blends (E0, E10, E22, E85W, E85S, E100). METHODS: Exhaust emissions from vehicles using ethanol blends were delivered to a photochemical chamber and reacted to produce SOA. The aerosol samples were collected on filters, extracted, and dispersed in an aqueous solutions and intratracheally instilled into Sprague Dawley rats in doses of 700 µg/0.2 ml. After 45 min and 4 h pulmonary and cardiac chemiluminescence (CL) was measured to estimate the amount of reactive oxygen species (ROS) produced in the lungs and heart. Inflammation was measured by differential cell count in bronchoalveolar lavages (BAL). RESULTS: Statistically and biologically significant differences in response to secondary particles from the different fuel formulations were detected. Compared to the control group, animals exposed to SOA from gasoline (E0) showed a significantly higher average CL in the lungs at 45 min. The highest CL averages in the heart were observed in the groups exposed to SOA from E10 and pure ethanol (E100) at 45 min. BAL of animals exposed to SOA from E0 and E85S had a significant increased number of macrophages at 45 min. BAL neutrophil count was increased in the groups exposed to E85S (45 min) and E0 (4 h). Animals exposed to E0 and E85W had increased BAL lymphocyte count compared to the control and the other exposed groups. DISCUSSION: Our results suggest that SOA generated by gasoline (E0), followed by ethanol blends E85S and E85W, substantially induce oxidative stress measured by ROS generation and pulmonary inflammation measured by the recruitment of white blood cells in BAL.


Assuntos
Poluentes Atmosféricos/toxicidade , Pneumonia/induzido quimicamente , Espécies Reativas de Oxigênio/metabolismo , Emissões de Veículos/toxicidade , Animais , Etanol , Gasolina , Coração/efeitos dos fármacos , Contagem de Leucócitos , Pulmão/efeitos dos fármacos , Macrófagos/citologia , Neutrófilos/citologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
7.
Bioelectrochemistry ; 129: 170-178, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31181439

RESUMO

Our aim was to investigate if the cardioplegic solution HTK can be improved by the addition of the ROS scavenger melatonin. 158 guinea pig hearts without (UI80) or with HTK protection (HTK80) were investigated in ischemia/reperfusion experiments. Ischemia lasted 80 min at 30 °C. Melatonin was given before ischemia (UI80 + M1, HTK80 + M1) or before and after ischemia (UI80 + M2, HTK80 + M2). We measured the left ventricular developed pressure (LVDP), diastolic pressure (LVPmin), cardiac rhythm (VC-RR), time of electrical cell uncoupling (t-in) and recovery (t-ret), intracellular Ca++ [Ca++], and postischemic ROS. After 45 min reperfusion, LVDP in UI80 was significantly higher than in HTK80 (p < .01). Compared to UI80, the postischemic ROS burst was slightly smaller in HTK80 and significantly smaller in HTK80 + M1 and HTK80 + M2 (p < .05). Melatonin had no effect on LVPmin, t-in, t-ret, [Ca++], and on LVDP in groups UI80 + M1 and HTK80 + M1, improved slightly VC-RR (n. s.) but significantly decreased LVDP in the groups UI80 + M2 and HTK80 + M2 (p < .01). With melatonin we were able to attenuate the postischemic ROS burst, but the tissue damage by ROS seemed to be less important for the chosen ischemia condition because melatonin was unable to improve the functional recovery during reperfusion of HTK protected hearts.


Assuntos
Soluções Cardioplégicas/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Parada Cardíaca Induzida/métodos , Coração/efeitos dos fármacos , Melatonina/uso terapêutico , Traumatismo por Reperfusão Miocárdica/terapia , Animais , Feminino , Cobaias , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/cirurgia
8.
Sci Total Environ ; 683: 624-637, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31150883

RESUMO

The non-steroidal anti-inflammatory drug diclofenac (DCF) threatens the health of aquatic animals and ecosystems. In the present study, different biological endpoints (mortality, development and growth, abnormalities, cardiotoxicity, neurotoxicity and antioxidant system) were used to characterize the acute and chronic effects of DCF (at concentrations ranging between 125 and 4000 µg L-1) on two amphibian species from Argentina (Trachycephalus typhonius and Physalaemus albonotatus). Results showed that the larval developmental, growth rates, and body condition of DCF-exposed individuals of both species were significantly reduced. DCF-exposed individuals also showed several morphological abnormalities, including significantly altered body axis, chondrocranium and hyobranchial skeleton, and organ and visceral abnormalities including cardiac hypoplasia, malrotated guts, asymmetrically inverted guts, and cholecystitis. DCF also had a significant effect on the swimming performance of both species: at low concentrations (125 and 250 µg L-1), swimming distance, velocity and global activity decreased, whereas, at high concentrations (1000 and 2000 µg L-1), these behavioral responses increased. Regarding cardiac function and rhythm, at DCF concentrations higher than 1000 µg L-1, the heart frequency and ventricular systole interval of both species were significantly reduced. Regarding the antioxidant system, the activity of acetylcholinesterase indicated that DCF is neurotoxic and thus related to the changes in behavioral performance. The DCF concentrations studied produced a biochemical imbalance between radical oxygen species production and antioxidant systems. The sensitivities to sublethal and chronic DCF exposure in both anuran species were similar, thus indicating the inherent complexity involved in understanding the biotoxic effects of DCF.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Anuros/fisiologia , Diclofenaco/toxicidade , Coração/fisiologia , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Animais , Coração/efeitos dos fármacos , Larva/efeitos dos fármacos , Testes de Toxicidade
9.
J Toxicol Sci ; 44(6): 373-391, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31168026

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic class in clinical medicine. These are sub-divided based on their selectivity for inhibition of cyclooxygenase (COX) isoforms (COX-1 and COX-2) into: (1) non-selective (ns-NSAIDs), and (2) selective NSAIDs (s-NSAIDs) with preferential inhibition of COX-2 isozyme. The safety and pathophysiology of NSAIDs on the renal and cardiovascular systems have continued to evolve over the years following short- and long-term treatment in both preclinical models and humans. This review summarizes major learnings on cardiac and renal complications associated with pharmaceutical inhibition of COX-1 and COX-2 with focus on preclinical to clinical translatability of cardio-renal data.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Humanos , Rim/metabolismo , Miocárdio/metabolismo
10.
Artigo em Chinês | MEDLINE | ID: mdl-31245950

RESUMO

OBJECTIVE: To study the effects of notoginseng, gingko leaf and rhodiola on cardiac functions and the serum inflammatory factors interleukin-6,interleukin-10, and TNF-α of rats with hypoxia deacclimatization, to explore the mechanism of hypoxia detoxification. METHODS: Forty SD rats were randomly divided into notoginseng group(n=10), gingko leaf group(n=10), rhodiola group(n=10) and high altitude control group(n=10) after fed in a hypobaric hypoxia chamber(simulated altitude of 5 000 m) for 3 month, while 10 rats fed at normal pressure and oxygen environment for 3 month were used as the plain control group. Rats in notoginseng group, gingko leaf group and rhodiola group were treated with notoginseng, gingko leaf tablets or rhodiola suspension through intragastric administration (200 mg/kg,twice a day, for 10 days). After the rats got intraperitoneal anesthesia with 10% urethane, 5 min pulmonary artery pressure curve were traced continuously while pulmonary artery pressure (PAP). Left and right ventricular systolic pressure (VSP) and ventricular diastolic pressure (VEDP), the hemodynamic parameters were detected through a multi-channel physiological recorder. Serum tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. RESULTS: Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), mean pulmonary artery pressure (mPAP), left vent-ricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP),IL-6,and IL-10 were higher in notoginseng group, gingko leafgroup, rhodiola group and high altitude control group than those in plain control group(P<0.05 or P<0.01). The contents of MDA and TNF-α were higher while the level of SOD was lower in rhodiola group and high altitude control group than those in plain control group(P<0.01). The contents of MDA and TNF-α were lower while the level of SOD was higher in notoginseng group, gingko leaf group and rhodiola group than those in high altitude control group(P<0.01). The levels of RV,RVHI,RVSP,RVEDP,LVSP,LVEDP,IL-10 and TNF-α were statistically changed in notoginseng group than those in gingko leaf group and rhodiola group(P<0.05orP<0.01). CONCLUSION: Notoginseng, gingkoleaf and rhodiola can enhance antioxidant capacity of body and improve ventricular functions and Notoginseng, gingko leaf and rhodiola can effectively enhance the functions of ventricular and hypoxia tolerance and inhibit the expressions of inflammatory factors in rats during the hypoxia deacclimatization.


Assuntos
Ginkgo biloba , Coração , Hipóxia , Extratos Vegetais , Rhodiola , Animais , Ginkgo biloba/química , Coração/efeitos dos fármacos , Coração/fisiologia , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Rhodiola/química , Comprimidos
11.
Life Sci ; 232: 116579, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31252001

RESUMO

AIMS: We sought to evaluate the effects of maternal protein restriction (LP) on oxidative balance and transcription factors for mitochondrial biogenesis in the hearts of young female rats of both the first (F1) and second (F2) generation. MAIN METHODS: We evaluated oxidative stress biomarkers (lipid peroxidation and protein oxidation), enzymatic antioxidant defense (activity of superoxide dismutase-SOD, catalase, and glutathione-S-transferase-GST), nonenzymatic antioxidant defense (reduced glutathione-GSH and sulfhydryl groups) and gene expression of AMPK, PGC-1α and TFAM. KEY FINDINGS: Interestingly, lipid peroxidation was decreased (49%, p < 0.001) in the LP-F1 group and 59% (p < 0.001) in LP-F2. In enzymatic defense, we observed increases in SOD activity in the LP-F1 group (79%, p = 0.036) and in CAT activity (approximately 40%, p = 0.041). GSH was increased in F2 in both groups (LP 546%, p < 0.0001 and in NP 491.7%, p < 0.0001). With respect to mitochondrial biogenesis gene transcription, we observed a decrease in AMPK (60%, p < 0. 0001) and an increase in PGC-1α (340%, p < 0.001) in LP compared to NP in the F1 generation. TFAM was decreased in LP-F2L compared to NP-F2L (42%, p = 0.0069) and increased in LP-F2 compared to LP-F1 (160%, p = 0.0037). SIGNIFICANCE: Our study contributes to knowledge of inheritance, showing that despite the potential mitochondrial 'inheritance' of cardiovascular damage caused by maternal malnutrition, that damage is not cross-generational and can be eliminated with proper nutrition in the F1 generation.


Assuntos
Miocárdio/metabolismo , Estresse Oxidativo/fisiologia , Desnutrição Proteico-Calórica/metabolismo , Animais , Antioxidantes/farmacologia , Feminino , Glutationa/metabolismo , Coração/efeitos dos fármacos , Coração/fisiologia , Hereditariedade/genética , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Biogênese de Organelas , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo , Fatores de Transcrição/metabolismo
12.
Aquat Toxicol ; 213: 105217, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31200331

RESUMO

Evidence of the ecological and biological impact of pharmaceuticals in surface waters on aquatic organisms is increasing. Tramadol is a synthetic opioid analgesic used to treat chronic and acute pain. To investigate its long-term effects at environmentally relevant levels, we evaluated heart rate (HR) and locomotion of signal crayfish Pacifastacus leniusculus during a 21-day exposure to 1 µg L-1 tramadol followed by 14 days depuration. Locomotion and HR were recorded over a period 30 min before and 30 min after exposure to physiological fluids of an injured conspecific, a natural stressor, four times during the tramadol exposure and four times during depuration. A significant increase in HR following stress induction was found in the majority of tramadol-exposed and control crayfish, as well as significant group-specific HR changes between both groups. Locomotor activity during tramadol treatment differed from that during depuration, in general showing less time spent in locomotion and lower distance moved. The tramadol exposed crayfish exhibited higher velocity during depuration than during the exposure period. Results may suggest a potential shift in prey-predator relationships.


Assuntos
Astacoidea/fisiologia , Comportamento Animal/efeitos dos fármacos , Coração/fisiologia , Estresse Fisiológico/efeitos dos fármacos , Tramadol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Astacoidea/efeitos dos fármacos , Exposição Ambiental/análise , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Fatores de Tempo
13.
Aquat Toxicol ; 213: 105218, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203168

RESUMO

The toxic effects of different atrazine concentrations on tadpoles and adult male African clawed frogs (Xenopus laevis) were assessed in a controlled laboratory environment following 90 days' exposure. The aim was to elucidate the danger of atrazine exposure on the cardiac tissue relative to its critical function of rhythmic contractility, fundamental for optimal blood circulation and homeostasis. Tadpoles and adult frogs were exposed to 0 µg/L (control), 0.01 µg L-1, 200 µg L-1 and 500 µg L-1 concentrations of atrazine for 90 days. Mortality was concenration-dependent and significantly increased in juvenile group (77%, 43%, 23% and 0 respectively for 500 µg L-1, 200 µg L-1, 0.01 µg L-1, and control group). While the mean juvenile heart area decreased concentration-dependently, adult frog mean heart area significantly increased in the 200 µg L-1 group only and mean heart weight change was variable across all exposure levels. Light microscopy of hematoxylin and eosin (H&E) and Mallory-Heidenhain rapid one-step staining techniques on cardiac tissue sections of the juvenile and adult frogs revealed shrinkage of cardiac muscle cells into thin wavy myocytes. Additionally, disorganized branching of muscle fibres with reduced striations were observed in 0.01 µg L-1 and 200 µg L-1 but hypertrophied myocytes, thickened intensely staining myofibrils in the 500 µg L-1 group in juvenile and adult frogs. Significant increase in the mean percentage area of connective tissue in all the treated groups (p < 0.036) were also recorded. Immunohistochemistry analysis showed decreased eNOS localization in cardiac tissue in 200 µg L-1 and 500 µg L-1 of both juvenile and adult group, suggestive of decreased cardiac contractility due to atrazine exposure. The results indicate that environmentally relevant atrazine concentrations cause significant mortality in tadpoles while concentrations ≥200 µg L-1 adversely affect cardiac muscle morphology and may induce functional perturbations in cardiac tissue contractility and consequent dysfunction which generally may have an adverse impact on their survival and longevity.


Assuntos
Atrazina/toxicidade , Cardiotoxicidade/patologia , Poluentes Químicos da Água/toxicidade , Xenopus laevis/fisiologia , Animais , Tecido Conjuntivo/efeitos dos fármacos , Coração/efeitos dos fármacos , Larva/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Análise de Sobrevida
14.
Fa Yi Xue Za Zhi ; 35(2): 224-229, 2019 Apr.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-31135119

RESUMO

Abstract: Objective To compare the differences of cardiotoxicity of alcohol extract from root, stem and leaf of Chloranthus serratus in the rats, and discuss preliminarily its mechanism of toxicity. Methods Rats were randomly divided into four groups: blank, root alcohol, stem alcohol and leaf alcohol, with 8 in each group. After 14 days of continuous intragastric administration, the body mass change curves were drawn. The cardiac coefficient was calculated. The contents of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and α-hydroxybutyrate dehydrogenase (α-HBDH) as well as the content changes of oxidative stress indexes - total superoxide dismutase (T-SOD) and malondialdehyde (MDA) in the serum of rats were detected. The cardiac pathomorphology changes in the rats were observed. The expression of intercellular adhesion molecule (ICAM-1) and heme oxygenase (HO-1) in myocardial tissue was detected. Results Body mass growth rate: stem alcohol group was the smallest, followed by leaf alcohol group. The difference of cardiac coefficient of every group had no statistical significance (P>0.05). The myocardial tissues of stem alcohol group suffered the most serious damage, followed by the leaf alcohol group. The contents of CK, CK-MB, LDH and α-HBDH in stem alcohol group increased (P<0.05). The increase of MDA content and decrease of T-SOD content in stem alcohol group had statistical significance compared with the blank group and root alcohol group, while the leaf alcohol group only had statistical significance in the decrease of T-SOD content compared with the blank group (P<0.05). The positive expression of ICAM-1 enhanced and the expression of HO-1 protein decreased in every group after the intervention of different extracts. The change trend was stem alcohol > leaf alcohol > root alcohol group. Conclusion The alcohol extract from the stem has the highest cardiotoxicity, followed by the leaf extract, and its mechanism of toxicity may be related to oxidative stress.


Assuntos
Cardiotoxicidade , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Estresse Oxidativo/fisiologia , Extratos Vegetais/toxicidade , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Animais , Etanol , Malondialdeído , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
15.
Environ Pollut ; 251: 564-572, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31108289

RESUMO

The phenylpyrazole insecticide, fipronil, isused for the eradication of insects in agriculture, which also exposes various non-target groups such as birds and animals. Our aim was to assess the cardiac and pulmonary consequences of sub-acute administration of fipronil (1∕5 LD50; 2.26 mg/kg) in the Japanese quail for fifteen days and to determine the tissue recovery over a period of 60 days. Fipronil exposure led to a significant decrease in the body weight of the treated birds. Its exposure also induced cardiac and pulmonary damage of varying degrees. Fipronil increased the lipid peroxide (LPO) and nitric oxide (NO) contents as well as indices of tissue injury in the serum of exposed birds. Furthermore, it decreased the antioxidant indices in both the organs. Most of these changes gradually reversed and the histological changes, particularly of the heart, reversed completely by day-60 of recovery. Furthermore, alterations in the mRNA gene expressions of Nuclear factor kappa B (NF-κB), Interleukin 6 (IL-6), and Tumor necrosis factor-alpha (TNF-α) were monitored by quantitative polymerase chain reaction (RT-PCR). In both the tissues, a significant up-regulation of the transcripts was recorded after fipronil administration, which was reversed during the recovery period in the heart tissue except for TNF-α, while the transcripts in the lung tissue declined non-significantly. This study showed that the exposure of Japanese quail to fipronil has a profound negative impact on heart and lung including oxidative injury and tissue inflammation. Fipronil can induce the activity of NF-κB inflammatory -signaling pathway that play a role in the associated tissue inflammation. Although most of the cardiac changes could be reversed after a recovery period of sixty days, the pulmonary changes did not reverse much.


Assuntos
Coturnix/genética , Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Inseticidas/toxicidade , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pirazóis/toxicidade , Animais , Antioxidantes/metabolismo , Inflamação , Interleucina-6/genética , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Miocárdio/imunologia , Miocárdio/metabolismo , NF-kappa B/genética , Estresse Oxidativo/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Testes de Toxicidade , Fator de Necrose Tumoral alfa/genética
16.
J Med Food ; 22(5): 479-489, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31084538

RESUMO

Among the comorbidities of high body mass index, cardiovascular disease continued to be the leading cause of death and disability globally in 2015, while type 2 diabetes remained second. The primary objectives of this observational study were to confirm the safety, tolerability, and efficacy of our calorie-restricted Mediterranean diet with targeted dietary supplementation (PROG1) using globally recognized dietary supplementation. Fifty healthy overweight and obese subjects with cardiometabolic risk factors were assigned a modified Mediterranean diet, including protein shakes and targeted supplementation (PROG2), providing ∼68-76% of subject estimated calorie requirements. Salivary nitrite was assessed weekly and key cardiometabolic metrics were recorded at baseline and weeks 9 and 13. PROG2 was well tolerated with 86% compliance. The most common adverse effects were bloating, flatulence, and constipation, which were self-limiting. Subjects exhibited decreases (P < .01) from baseline of 12% in body weight, 18% in body fat, and 8.8% in waist circumference. Total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) were reduced (P < .01), respectively, 19%, 22%, and 40%. Lipid ratios of TC/high-density lipoprotein (HDL), TG/HDL, and oxidized LDL (oxLDL)/HDL were decreased 15% (P < .01), 35% (P < .01), and 13% (P < .05), respectively. Inflammation biomarkers, oxLDL and high-sensitivity C-reactive protein, were reduced 17% (P < .01) and 30% (P < .05), respectively. Reductions of 9.0% for systolic (P < .01) and 12% (P < .01) for diastolic blood pressure were noted. In concert, the nitrogen dioxide salivary biomarker for nitric oxide was increased relative to baseline. PROG2 produced a dramatic 50% reduction in subjects meeting cardiometabolic syndrome criteria and a 38% decrease in Framingham 10-year cardiovascular risk. These results confirmed our previous findings that the addition of targeted nutraceutical supplementation to a calorie-restricted Mediterranean diet with lifestyle modifications improves multiple longevity risk factors more effectively than diet and lifestyle modification alone.


Assuntos
Dieta Mediterrânea , Miocárdio/metabolismo , Sobrepeso/dietoterapia , Extratos Vegetais/administração & dosagem , Probióticos/administração & dosagem , Adulto , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Colesterol/metabolismo , Suplementos Nutricionais/análise , Feminino , Índice Glicêmico , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Estilo de Vida , Longevidade/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Sobrepeso/tratamento farmacológico , Sobrepeso/fisiopatologia , Sobrepeso/psicologia , Triglicerídeos/metabolismo
17.
Environ Toxicol ; 34(7): 878-885, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037826

RESUMO

Perfluorooctanoic acid (PFOA) is an octanoic acid and is found in wildlife and humans. We have investigated mitochondrial toxicity in isolated mitochondria from, placenta, brain, liver, and heart after oral exposure with PFOA in mice during gestational days (7-15). Histopathological examination and mitochondrial toxicity parameters were assayed. Results indicated that PFOA decreased the weight of the fetus and placenta, the length of the fetus and the diameter of the placenta, dead fetuses and dead macerated fetuses in treated mice with 25 mg/kg. Histopathological examination showed that PFOA induced pathological abnormalities in liver, brain, heart, and placenta. Also, PFOA induced mitochondria toxicity in brain, liver, heart of mouse fetus. Our results indicate that PFOA up to 20 mg/kg exposure adversely affect embryofetal/developmental because for mitochondria dysfunction. These results suggested that mitochondrial dysfunction induced by PFOA in liver, heart, and brain lead to developmental toxicity and abnormality in tissues.


Assuntos
Aborto Espontâneo/induzido quimicamente , Caprilatos/toxicidade , Desenvolvimento Fetal/efeitos dos fármacos , Feto/efeitos dos fármacos , Fluorcarbonetos/toxicidade , Exposição Materna/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Anormalidades Induzidas por Medicamentos/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/ultraestrutura , Feminino , Feto/metabolismo , Feto/patologia , Coração/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/ultraestrutura , Masculino , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/fisiologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/fisiologia , Miocárdio/ultraestrutura , Gravidez
18.
Life Sci ; 230: 19-27, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125563

RESUMO

AIMS: We investigated the effect of the selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin on cardiac dysfunction and histopathology in a non-diabetic rat model of cardiomyopathy. MAIN METHODS: Ipragliflozin was mixed with chow (0.01%, w/w) and administered to male DahlS.Z-Leprfa/Leprfa (DS/obese) rats for 8 weeks. Male DahlS.Z-Lepr+/Lepr+ (DS/lean) rats of the same age were used as controls. Systolic blood pressure (SBP) and heart rate (HR) were measured every 4 weeks. After 8 weeks of treatment, echocardiography and histopathological examinations were performed. Further, the effect of ipragliflozin on blood and urine parameters were investigated. KEY FINDINGS: In the DS/obese rats, ipragliflozin delayed the age-related increase in SBP without affecting HR, reduced left ventricular (LV) mass and intraventricular septal thickness in echocardiography, and ameliorated hypertrophy of cardiomyocytes and LV fibrosis in histopathological examination. Although ipragliflozin significantly increased both urine volume and urinary glucose excretion in DS/obese rats, it did not alter plasma glucose levels. SIGNIFICANCE: Ipragliflozin prevented LV hypertrophy and fibrosis in non-diabetic DS/obese rats without affecting plasma glucose levels. These findings suggest that SGLT2 inhibitors have a cardio-protective effect in non-diabetic patients with cardiomyopathy.


Assuntos
Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/patologia , Glucosídeos/farmacologia , Tiofenos/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Ecocardiografia , Fibrose/tratamento farmacológico , Fibrose/prevenção & controle , Glucosídeos/metabolismo , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/prevenção & controle , Hipoglicemiantes/farmacologia , Masculino , Síndrome Metabólica/fisiopatologia , Obesidade , Ratos , Ratos Endogâmicos Dahl , Transportador 2 de Glucose-Sódio/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Sístole/efeitos dos fármacos , Tiofenos/metabolismo
19.
Life Sci ; 229: 251-260, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31112711

RESUMO

AIMS: Cardiovascular diseases may originate from suboptimal intrauterine environments. We aimed to examine the effects of prenatal androgen exposure (PAE) on heart basal hemodynamic parameters and tolerance to ischemia/reperfusion (I/R) injury, in PAE adult females and males. MAIN METHODS: Pregnant Wistar rats in the experimental group (n = 8) received 5 mg of testosterone (s.c. injection) on the 20th day of pregnancy, while controls received solvent. The hearts of adult female and male offspring were isolated and perfused in a Langendorff apparatus, values of left ventricular systolic pressure(LVSP), left ventricular developed pressure(LVDP), rate pressure product(RPP) and peak rates of positive and negative changes in left ventricular pressure(±dp/dt) were recorded using a power lab system. KEY FINDINGS: At baseline, PAE adult males demonstrated significant higher values of LVSP, LVDP, RPP and ±â€¯dp/dt, compared to controls and PAE adult females (p < 0.05), while PAE adult females showed no significant differences compared to controls. In PAE adult males, LVSP, LVDP, RPP and ±â€¯dp/dt had significant decreasing trends per phases after I/R, compared to their controls and PAE females, while these decreasing trends were not statistically significant in PAE adult female rats vs. their controls. SIGNIFICANCE: The impact of prenatal androgen exposure on adulthood cardiac function and tolerance to I/R is gender dependent, which may be partly explained by different cardiac effects of hyperandrogenism in males versus females. After prenatal androgen exposure, the baseline hemodynamic parameters of the hearts of adult males are increased; although they had less tolerance to I/R, findings however not observed in females.


Assuntos
Androgênios/administração & dosagem , Tolerância a Medicamentos , Coração/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Animais , Pressão Sanguínea , Feminino , Coração/efeitos dos fármacos , Hemodinâmica , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Gravidez , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Ratos , Ratos Wistar
20.
Ter Arkh ; 91(1): 114-128, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090382

RESUMO

The review presents the results of a number of experimental and clinical studies proving the prospects of using L-carnitine in the clinic of internal diseases. Due to the antioxidant and antihypoxant properties, the additional use of L-carnitine in addition to the main etiopathogenetic therapy is prescribed by cardiologists, nephrologists, neurologists, gerontologists. Experimental studies we conducted earlier showed no effect of L-carnitine on the activity of the P450 CYP 3A4 system, which reduces the likelihood of drug-drug interaction at the level of metabolism of drugs metabolized by P450 3A4. When using L-carnitine as part of complex pharmacotherapy, the drug has an increased safety profile in comorbid patients taking L-carnitine. Keywords: L-carnitine, P450 CYP 3А4, chronic heart failure, myocardial infarction, chronic renal failure, inter-drug interaction, antioxidant, antihypoxant.


Assuntos
Antioxidantes/farmacologia , Carnitina/farmacologia , Citocromo P-450 CYP3A/metabolismo , Cardiopatias/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Coração/efeitos dos fármacos , Falência Renal Crônica/metabolismo , Infarto do Miocárdio/complicações , Antioxidantes/metabolismo , Carnitina/metabolismo , Carnitina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Medicina Interna , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo
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