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1.
Rev Med Suisse ; 16(683): 404-408, 2020 Feb 26.
Artigo em Francês | MEDLINE | ID: mdl-32129017

RESUMO

Cheap and easy to access, ethylene glycol is used in the synthesis of antifreezes. Intoxication has potentially irreversible morbid consequences. Ingestion of a small amount can lead to death. Due to its ubiquitous distribution and potential complications, it is of paramount importance for the practitioner to recognize its manifestations and metabolic complications in order to implement its therapy in partnership with the nephrologist and the intensivist. A successful treatment depends on rapid and multidisciplinary management, as reviewed in this article.


Assuntos
Etilenoglicol/toxicidade , Nefropatias/induzido quimicamente , Humanos
2.
Artigo em Inglês | MEDLINE | ID: mdl-31782949

RESUMO

Background Naturally ripened fruits play a vital role in human nutrition. Under certain conditions, synthetic chemicals like calcium carbide (CaC2) and ethylene glycol (EG) are being freely used illegally in India and other countries for fruit ripening without serious concern on its toxic effects. This preclinical study evaluated the toxicity on different organs after the exposure of industrial-grade CaC2 and EG to the rats. Methods Acute toxicity was induced by the oral administration of a single dose of chemicals to the rats, and their morbidity and mortality were monitored. For subacute study, different organs of animals were analyzed biochemically and histologically after the exposure of low doses of chemicals for 30 days. Results At an acute dose of 5 mg/kg body weight of CaC2, 85% of the animals were found dead within 14 days; however, no mortality was observed following EG administration. At subacute doses, RBC and hemoglobin levels were found to be declined (p < 0.01), whereas total WBC and platelet counts, especially lymphocytes, were elevated remarkably (p < 0.01). Total protein, albumin, and urea were also found to be increased (p < 0.01). Histopathological observations support the toxicity in rats at higher doses of CaC2 and EG. Conclusions The study revealed that the artificial fruit-ripening agents like CaC2 and EG cause toxic effects on the internal organs of rats. The subsequent inflammatory response might have weakened the immune system. This in turn suggests the requisite for urgent measures to regulate the use of harmful synthetic agents in fruit ripening.


Assuntos
Acetileno/análogos & derivados , Etilenoglicol/toxicidade , Acetileno/toxicidade , Administração Oral , Albuminas/metabolismo , Animais , Frutas/química , Hemoglobinas/metabolismo , Índia , Masculino , Ratos , Ratos Wistar , Testes de Toxicidade Aguda/métodos
3.
Urol J ; 16(6): 519-524, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31473993

RESUMO

PURPOSE: This study aimed to evaluate the anti-inflammatory effect of E. campestre using the aqueous extracts, obtained from the aerial parts, on Ethylene Glycol (EG)-induced calcium oxalate kidney stone in rats. MATERIALS AND METHODS: 64 male Wistar rats were randomly divided into 8 groups. Group I was considered as negative control and received normal saline for 30 days, group II as kidney stone control received EG for 30 days, groups III to VI as prophylactic treatment received EG plus 100, 200 or 400 mg/kg extracts for 30 days and groups VI to VIII received EG as therapy from day one and 100, 200 or 400 mg/kg extract from the 15th day. On the 30thday from the start of induction, rats were euthanized. Blood was collected and the kidneys were immediately excised. Slides from each one's kidneys were prepared and stained with Hematoxylin & Eosin method. Also levels of interleukin-1 beta (IL-1?) and interleukin-6 (IL-6) were determined in rat's serum by competitive ELISA kit. RESULTS: E. campestre reduced IL-1? and IL-6 levels, showing a significant reduction for both cytokines in all prophylactic groups, especially at the dose of 400 mg/kg (P-value < .001). Moreover, IL-1? (p = .011) reduced significantly in the therapy groups in 400 mg/kg dose. Crystal count reduction was seen in all prophylactic and therapy groups in comparison with group II. CONCLUSION: These results suggest that the E. campestre extract has potent suppressive effect on pro-inflammatory cytokine production in rat. Also, E. campestre decreases crystal deposition in the kidney of the hyperoxaluric rat.


Assuntos
Oxalato de Cálcio/metabolismo , Eryngium , Nefrolitíase/terapia , Extratos Vegetais/uso terapêutico , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etilenoglicol/toxicidade , Masculino , Nefrolitíase/induzido quimicamente , Nefrolitíase/diagnóstico , Fitoterapia , Ratos , Ratos Wistar
4.
Int J Urol ; 26(8): 839-846, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31257672

RESUMO

OBJECTIVES: To study the promotive effect of salt-induced hypertension on crystal deposition and urolithiasis using a salt-sensitive rat hypertension model. METHODS: Hyperoxaluria and hypercalciuria were induced in male Dahl salt-sensitive rats with administration of ethylene glycol and alfacalcidol. Hypertension was induced by a high-salt diet. Eplerenone, a selective mineralocorticoid receptor antagonist, was given. Blood and urine were collected to evaluate renal function, electrolytes and the blood renin-angiotensin-aldosterone system. Renal calcium content was also evaluated. Histological examination, transcriptome analysis with DNA microarray and semiquantitative reverse transcriptase polymerase chain reaction were carried out. RESULTS: A high-salt diet increased crystal deposition in Dahl salt-sensitive rats with hypertension, and eplerenone administration significantly suppressed it. The mRNA expression profile was associated with crystal formation, growth, adhesion and cellular injury, and it was regulated in the group exposed to a high-salt diet and ethylene glycol. CONCLUSIONS: A high-salt diet has a promotive effect on salt-sensitive hypertension and urolithiasis. This promotive effect can be prevented by eplerenone administration. Hence, salt-sensitive hypertension has promotive effects on crystal deposition in Dahl salt-sensitive rats.


Assuntos
Hipertensão/etiologia , Cloreto de Sódio na Dieta/efeitos adversos , Urolitíase/etiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cálcio/análise , Cálcio/metabolismo , Modelos Animais de Doenças , Eplerenona/administração & dosagem , Etilenoglicol/toxicidade , Humanos , Hidroxicolecalciferóis/toxicidade , Hipertensão/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Masculino , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Ratos , Ratos Endogâmicos Dahl , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Urolitíase/fisiopatologia , Urolitíase/prevenção & controle
5.
Cancer Epidemiol ; 59: 22-28, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30658217

RESUMO

OBJECTIVE: To examine the association between occupational exposure to petroleum-based and oxygenated solvents and the risk of oral and oropharyngeal cancer. METHODS: The ICARE study is a large population-based case-control study conducted in France between 2001 and 2007. This present analysis was restricted to men and included 350 and 543 cases of squamous cell-carcinoma of the oral cavity and oropharynx, respectively, and 2780 controls. Lifetime tobacco, alcohol consumption and complete occupational history were assessed through detailed questionnaires. Job-exposure matrices allowed us to assess occupational exposure to five petroleum-based solvents (white spirits; diesel/fuel oils/kerosene; gasoline; benzene; special petroleum products) and five oxygenated solvents (diethyl ether; tetrahydrofuran; ketones and esters; alcohols; ethylene glycol). Odds-ratios (ORs), adjusted for age, smoking, alcohol consumption and socioeconomic status, and 95% confidence intervals (CI) were estimated using unconditional logistic models. RESULTS: Associations between oral cancer risk and exposure to white spirits and diesel/fuel oils/kerosene were suggested, but there was no exposure-response trend. Concerning exposure to oxygenated solvents, participants with the highest levels of cumulative exposure to diethyl ether had a significant excess risk of oropharyngeal cancer (OR = 7.78, 95%CI 1.42 to 42.59; p for trend = 0.04). Ever exposure to tetrahydrofuran was associated with a borderline significant increased risk of oral cancer (OR = 1.87, 95%CI 0.97 to 3.61), but no exposure-response trend was observed. Additional adjustments for exposure to other solvents did not substantially change the results. CONCLUSION: Our results do not provide evidence for a major role of petroleum-based and oxygenated solvents in the occurrence of oral and oropharyngeal cancers in men.


Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Bucais/etiologia , Exposição Ocupacional/efeitos adversos , Neoplasias Orofaríngeas/etiologia , Petróleo/toxicidade , Solventes/toxicidade , Adulto , Idoso , Álcoois/toxicidade , Benzeno/toxicidade , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Éter/toxicidade , Etilenoglicol/toxicidade , França/epidemiologia , Óleos Combustíveis/toxicidade , Furanos/toxicidade , Gasolina/toxicidade , Humanos , Querosene/toxicidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/epidemiologia , Razão de Chances , Neoplasias Orofaríngeas/induzido quimicamente , Neoplasias Orofaríngeas/epidemiologia
6.
Cryobiology ; 86: 95-102, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30458175

RESUMO

We report here a new, unbiased forward genetic method that uses transposon-mediated mutagenesis to enable the identification of mutations that confer cryoprotectant toxicity resistance (CTR). Our method is to select for resistance to the toxic effects of M22, a much-studied whole-organ vitrification solution. We report finding and characterizing six mutants that are resistant to M22. These mutants fall into six independent biochemical pathways not previously linked to cryoprotectant toxicity (CT). The genes associated with the mutations were Gm14005, Myh9, Nrg2, Pura, Fgd2, Pim1, Opa1, Hes1, Hsbp1, and Ywhag. The mechanisms of action of the mutations remain unknown, but two of the mutants involve MYC signaling, which was previously implicated in CT. Several of the mutants may up-regulate cellular stress defense pathways. Several of the M22-resistant mutants were also resistant to dimethyl sulfoxide (Me2SO), and many of the mutants showed significantly improved survival after freezing and thawing in 10% (v/v) Me2SO. This new approach to overcoming CT has many advantages over alternative methods such as transcriptomic profiling. Our method directly identifies specific genetic loci that unequivocally affect CT. More generally, our results provide the first direct evidence that CT can be reduced in mammalian cells by specific molecular interventions. Thus, this approach introduces remarkable new opportunities for pharmacological blockade of CT.


Assuntos
Criopreservação/métodos , Crioprotetores/farmacologia , Crioprotetores/toxicidade , Células-Tronco Embrionárias/citologia , Estresse Fisiológico/genética , Supressão Genética/genética , Animais , Linhagem Celular , Elementos de DNA Transponíveis/genética , Dimetil Sulfóxido/farmacologia , Dimetil Sulfóxido/toxicidade , Etilenoglicol/farmacologia , Etilenoglicol/toxicidade , Formamidas/farmacologia , Formamidas/toxicidade , Congelamento , Camundongos , Camundongos Endogâmicos C57BL , Mutagênese/genética , Estresse Fisiológico/efeitos dos fármacos , Vitrificação/efeitos dos fármacos
7.
Urolithiasis ; 47(2): 171-179, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29947992

RESUMO

Hyperoxaluria is characterized by an increased excretion of urinary oxalate which is caused by inherited disorders or high oxalate intake leading to renal stone ailment. Until date, reactive oxygen species and inflammation has been convicted for the progression of kidney stones for which antioxidant therapy has been employed. However, recent studies have linked the association of endoplasmic reticulum stress and oxidative imbalance in the progression of renal diseases. Considering oxidative stress being at forefront in causing hyperoxaluric consequences, current study was designed to correlate the impact of hyperoxaluria and regulation of oxidative imbalance via inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid (4-PBA). Male wistar rats were subdivided into three groups, i.e., normal control (C), hyperoxaluric rats given ethylene glycol (EG), and hyperoxaluric rats treated with 4-PBA (EG + PBA). After 28 days of treatment, assessment of antioxidant defence system, inflammation, ER stress, and subsequent unfolded protein response was studied in renal tissue. It was found that the hyperoxaluric insult led to a marked damage to the renal tissue resulting in compromised antioxidant levels, upregulation of ER stress markers along with a steep surge in the extent of inflammation. However, 4-PBA treatment significantly curtailed the deleterious effects of hyperoxaluria by lowering down the level of stress markers as well as normalizing the antioxidant defence enzymes. Therefore, chemical chaperones can be deemed as a new class of drugs for the treatment of hyperoxaluric induced renal damage.


Assuntos
Hiperoxalúria/complicações , Cálculos Renais/prevenção & controle , Rim/efeitos dos fármacos , Fenilbutiratos/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Animais , Biomarcadores/análise , Oxalato de Cálcio/urina , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Etilenoglicol/toxicidade , Humanos , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/urina , Rim/patologia , Rim/fisiopatologia , Cálculos Renais/etiologia , Cálculos Renais/fisiopatologia , Cálculos Renais/urina , Masculino , Fenilbutiratos/uso terapêutico , Ratos , Ratos Wistar
8.
Syst Rev ; 7(1): 250, 2018 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-30593287

RESUMO

BACKGROUND: Toxic alcohols have been implicated in accidental ingestions and intentional exposures. Recognition of toxic alcohol poisoning is challenging. The main treatment modalities include antidotes with alcohol dehydrogenase inhibitors and dialysis. Current guidelines exist for both methanol and ethylene glycol intoxication. However, treatment consensus related to other toxic alcohols is limited. Furthermore, uncertainties regarding thresholds for when to initiate antidotes and dialysis persist. As a consequence, variations exist in the interventions utilized for management of all toxic alcohol poisonings. To our knowledge, no prior systematic review of clinical outcomes of toxic alcohols exists. The objective of this study is to summarize existing evidence on short- and long-term outcomes of patients following toxic alcohol poisonings, including methanol, ethylene glycol, isopropanol, propylene glycol, and diethylene glycol. METHODS: A literature search in PubMed, MEDLINE, and EMBASE will be performed based on pre-determined criteria. There will be no restrictions on publication dates or languages. The search will be supplemented by manual scan of bibliographies of eligible studies and gray literature assessment. Observational studies and clinical trials will be included in this review. Once eligible studies have been selected based on pre-specified criteria, two investigators will extract relevant data independently and perform quality assessment per validated tools. A pooled analysis of mortality and short- and long-term secondary outcomes will be performed. Pre-specified subgroup analyses will be performed according to the type of toxic alcohol intoxication, mode of renal replacement therapy, and medical interventions received. A meta-analysis will be performed if three or more studies with similar populations, type of toxic alcohol poisoning, and outcome measures, as well as adequate quality, are identified. This review will be reported according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Statement. DISCUSSION: This systematic review aims to synthesize current evidence in the short- and long-term outcomes of post-toxic alcohol poisoning. The results will enhance the understanding of patient morbidity and mortality after toxic alcohol poisoning, help inform uniform concrete management guideline development, identify gaps in the current state of knowledge, and provide evidence to help implement post-treatment follow-up. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018101955.


Assuntos
Etilenoglicol/toxicidade , Metanol/toxicidade , Resultado do Tratamento , Antídotos/uso terapêutico , Protocolos Clínicos/normas , Humanos , Diálise Renal/métodos
9.
Ecotoxicol Environ Saf ; 163: 349-355, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30059879

RESUMO

The conventional emulsifiable concentrate (EC) formulation contains a large amount of aromatic solvents, which causes adverse effects to both the environment and human health due to the toxicity of the solvents. Here, we developed a 2.5% lambda-cyhalothrin EC formulation with ethylene glycol diacetate (EGDA) as the solvent, and the developed formulation serves as an environmental-friendly alternative to overcome the adverse effects of aromatic solvents. The physicochemical characterizations, wettability properties, phytotoxicity and bioassays of the EGDA-EC formulation were systematically investigated and compared with that of the EC formulation with xylene as the solvent. The results showed that both EC formulations had excellent emulsion properties and storage stabilities. Additionally, the EGDA-EC formulation possessed a higher flash point (96 °C), indicating safer production, storage and transport. The retentions of the EGDA-EC sample on leaves were 1.22-1.46-fold higher than that of the xylene-EC sample, and the EGDA-EC also exhibited lower surface tensions and contact angles, which would benefit decreasing drift-off and improving utilization. Furthermore, the bioassays demonstrated that the EGDA-EC formulation had lower acute toxicity to aquatic organisms and higher control efficacy to target insects compared with the xylene-EC formulation. Therefore, EGDA is a promising carrier for oil-soluble agrochemicals to improve their application performance and reduce their adverse effects.


Assuntos
Agroquímicos/administração & dosagem , Etilenoglicol/toxicidade , Nitrilos/administração & dosagem , Piretrinas/administração & dosagem , Agroquímicos/química , Agroquímicos/toxicidade , Animais , Brassica , Clorófitas , Cucumis sativus , Daphnia , Emulsões , Etilenoglicol/química , Humanos , Nitrilos/química , Nitrilos/toxicidade , Piretrinas/química , Piretrinas/toxicidade , Solventes , Tensoativos , Testes de Toxicidade , Peixe-Zebra
10.
Sci Justice ; 58(2): 85-89, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29526269

RESUMO

Entomotoxicology involves the analysis of the presence and the effects of toxicological substances in necrophagous insects. Results obtained by entomotoxicological studies may assist in the investigation of both the causes and the time of death of humans and animals. Ethylene glycol (EG) is easy to purchase, sweet and extremely toxic. It may be consumed accidentally or purposefully, in an attempt to cause death for suicidal or homicidal intent. Several cases report fatalities of humans and animals. The present study is the first to examine the effects of EG on the survival, developmental rate and morphology of two blowfly species, (Diptera: Calliphoridae) typically found on corpses and carcasses: Lucilia sericata (Meigen) and L. cuprina (Wiedemann). Both species were reared on substrates (beef liver) spiked with three different concentrations of EG that could cause death in either a human or cat: 1/2LD50 (T1), LD50 (T2), 2LD50 (T3), in addition to a control treatment (C) with no EG. Results of this research show that: a) both species are unable to survive if reared on a food substrate spiked with the highest concentration of EG (T3), while lower and medium concentrations (T1, T2) affect, but not prevent, the survival and the completion of the life cycle of such species; b) adults of L. sericata eclose only in C and T1, while adults of L. cuprina in both C, T1, T2; however, c) the developmental time of both species reared in T1 and T2 is statistically slower than the control; d) the body length of the immatures of both of the species reared in T1 and T2 is statistically smaller than the control.


Assuntos
Dípteros/efeitos dos fármacos , Dípteros/crescimento & desenvolvimento , Etilenoglicol/toxicidade , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Pupa/efeitos dos fármacos , Pupa/crescimento & desenvolvimento , Animais , Entomologia , Comportamento Alimentar , Ciências Forenses , Oviposição
11.
Scand J Work Environ Health ; 44(3): 310-322, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29405242

RESUMO

Objectives The etiology of male breast cancer (MBC) is largely unknown but a causal role of exposure to organic solvents has been suggested. Previous studies on occupational risk factors of breast cancer were often restricted to women who are frequently exposed to lower levels and at a lower frequency than men. We investigated the association between MBC and occupational exposure to petroleum and oxygenated and chlorinated solvents in a multicenter case-control study of rare cancers in Europe. Methods The study included 104 MBC cases and 1901 controls. Detailed lifetime work history was obtained during interviews, together with sociodemographic characteristics, medical history and lifestyle factors. Occupational exposures to solvents were estimated from a job-exposure matrix. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results Lifetime cumulative exposure to trichloroethylene >23.9 ppm years was associated with an increased MBC risk, compared to non-exposure [OR (95% CI): 2.1 (1.2-4.0); P trend <0.01). This increase in risk persisted when only exposures that occurred ≥10 years before diagnosis were considered. In addition, a possible role for benzene and ethylene glycol in MBC risk was suggested, but no exposure-response trend was observed. Conclusions These findings add to the evidence of an increased risk of breast cancer among men professionally exposed to trichloroethylene and possibly to benzene or ethylene glycol. Further studies should be conducted in populations with high level of exposure to confirm our results.


Assuntos
Neoplasias da Mama Masculina/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Solventes/toxicidade , Adulto , Idoso , Benzeno/toxicidade , Neoplasias da Mama Masculina/epidemiologia , Estudos de Casos e Controles , Etilenoglicol/toxicidade , Europa (Continente)/epidemiologia , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Tricloroetileno/toxicidade
12.
Urolithiasis ; 46(2): 149-155, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28260226

RESUMO

We previously developed an animal model of calcium oxalate (CaOx) deposition on the Malphigian tubules of Drosophila melanogaster as a model of urolithiasis. Here, we introduce a new tool for the study of anatomical structure for Drosophila. As a consequence of technical development, the invention of micro-computerized tomography (CT) has been introduced to the small animal, such as rat and mice. We used Drosophila as a model organism and fed the flies 0.5% lithogenic agent ethylene glycol for 3 weeks. Samples were simply prepared for further scanned by micro-CT to scan samples at 800 nm resolution. CT scanning was performed at 40 kVp of voltage, 250 µA of current, and 1750 ms of exposure time and without filter. Reconstruction of sections was carried out with the GPU-based scanner software. Specific region of interests was further analyzed by DataViewer software. Area with high radiologic density level was defined as CaOx deposition for further 3D analysis. Image of whole lithogenic Drosophila was compared with control. High radiologic density level was detected in the region of Malphigian tubules which can be identified as CaOx stones. There was no stone image in the control group. The image was the same as human non-contrast CT for the diagnosis of stone disease. Micro-CT clearly demonstrated the calcium oxalate calcifications in the Malphigian tubules of fruit fly. The image system provides that a new vision on study animal will facilitate further study of stone disease. With the development of new technology on micro-CT, more delicate and advanced image will be presented in the future.


Assuntos
Oxalato de Cálcio/metabolismo , Drosophila melanogaster , Túbulos de Malpighi/diagnóstico por imagem , Nefrolitíase/diagnóstico por imagem , Microtomografia por Raio-X/métodos , Animais , Modelos Animais de Doenças , Etilenoglicol/toxicidade , Humanos , Processamento de Imagem Assistida por Computador , Túbulos de Malpighi/patologia , Nefrolitíase/induzido quimicamente , Nefrolitíase/patologia , Software
13.
Urolithiasis ; 46(2): 157-166, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28616648

RESUMO

Dietary polyphenol caffeic acid (1) has been reported for various pharmacological activities. The aim of the current study was to investigate the effect of caffeic acid (1) on ethylene glycol-induced renal stones in rats. For the study, male Wistar rats were divided into seven groups; normal, pathological, and standard drug controls, and preventive and curative groups. Normal control group received drinking water for 8 weeks. Pathological, standard drug, preventive, and curative groups received 0.75% ethylene glycol in drinking water for the induction of calcium oxalate stone formation, along with the regular diet. Standard drug group received Urocit-K by gavage from day 1, while preventive and curative groups received caffeic acid (1) by gavage at doses of 20 and 40 mg/kg on day 1 and day 14, respectively. At the end of the experiment, urine analysis and kidney histopathology were performed. Real-time PCR was performed to evaluate the renal expression of the most important genes involved in urolithiasis, i.e., osteopontin, Tamm-Horsfall, prothrombin fragment 1, and bikunin genes. The results indicated that in both the preventive and curative groups, treatment of rats with caffeic acid (1) significantly regulated the altered biochemical parameters, along with the remarkable reduction of calcium oxalate deposits in the kidneys, as compared to the pathological group. Treatment with compound 1 also resulted in down-regulation of the osteopontin gene, and up-regulation of the prothrombin fragment 1, Tamm-Horsfall, and bikunin genes. These results suggest that caffeic acid (1) can be further investigated for the prevention, and treatment of kidney stones.


Assuntos
Antioxidantes/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Oxalato de Cálcio/metabolismo , Cálculos Renais/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Oxalato de Cálcio/urina , Modelos Animais de Doenças , Etilenoglicol/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Cálculos Renais/induzido quimicamente , Cálculos Renais/urina , Masculino , Citrato de Potássio/uso terapêutico , Ratos , Ratos Wistar , Eliminação Renal/efeitos dos fármacos
14.
Urolithiasis ; 46(3): 271-278, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28776078

RESUMO

Hypercalciuria is a main risk factor for kidney stone  formation. TRPV5 is the gatekeeper protein for mediating calcium transport and reabsorption in the kidney. In the present study, we tested the effect of TRPV5 activation with small activating RNA (saRNA), which could induce gene expression by targeting the promoter of the gene, on ethylene glycol (EG)-induced calcium oxalate (CaOx) crystals formation in rat kidney. Five pairs of RNA activation sequences targeting the promoter of rat TRPV5 were designed and synthesized. The synthesized saRNA with the strongest activating effect was selected, and transcellular calcium transportation was tested by Fura-2 analysis. Subsequently, Sprague-Dawley rats were equally divided into three groups and fed with water, 1% EG for 28 days after injecting the negative control saRNA, 1% EG for 28 days after injecting the selected TRPV5-saRNA, respectively. The CaOx crystal formation and the 24-h urine components were assessed. In vitro study, saRNA ds-320 could significantly activate the expression of TRPV5 and transcellular calcium transportation. In vivo study, after 28 days treatment of EG, rats pre-infected with saRNA ds-320 had lower urinary calcium excretion and renal CaOx crystals formation as compared to that pre-infected with negative control saRNA. Activation of TRVP5 with saRNA ds-320 could inhibit EG-induced calcium oxalate crystals formation via promoting urine calcium reabsorption and decreasing urine calcium excretion in rats.


Assuntos
Canais de Cálcio/genética , Oxalato de Cálcio/química , Hipercalciúria/genética , Cálculos Renais/genética , RNA de Cadeia Dupla/genética , Canais de Cátion TRPV/genética , Animais , Cálcio/metabolismo , Cálcio/urina , Oxalato de Cálcio/urina , Modelos Animais de Doenças , Etilenoglicol/toxicidade , Humanos , Hipercalciúria/metabolismo , Hipercalciúria/urina , Rim/metabolismo , Cálculos Renais/induzido quimicamente , Cálculos Renais/metabolismo , Cálculos Renais/urina , Masculino , Regiões Promotoras Genéticas , RNA de Cadeia Dupla/administração & dosagem , Ratos , Ratos Sprague-Dawley , Reabsorção Renal/genética , Ativação Transcricional/genética
15.
Nat Prod Res ; 32(10): 1180-1183, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28480748

RESUMO

This study investigated the effect of oral administration of Cactus fruit extracts on calcium oxalate deposition, malondialdehyde (MDA) and superoxide dismutase (SOD) activity in rat model. About 42 rats were used for the study. The animals were divided into seven groups. Control group maintained on regular rat food and drinking water throughout the study period, whereas in other groups nephrolithiasis was induced by ethylene glycol. Rats in kidney stone group were sacrificed after 28 days and all remaining groups after 58 days. Treatment groups were treated with 1 and 100 mg/kg of aqueous and ethanolic extracts of Cactus fruit for 30 days. After treatment, SOD activity was increased and MDA was decreased significantly. CaOx depositions were decreased significantly, especially in ethanolic extract of Cactus fruit in high dose (100 mg/kg).


Assuntos
Cálculos Renais/tratamento farmacológico , Opuntia/química , Extratos Vegetais/farmacologia , Animais , Oxalato de Cálcio/metabolismo , Etanol/química , Etilenoglicol/toxicidade , Frutas/química , Cálculos Renais/induzido quimicamente , Masculino , Malondialdeído/metabolismo , Ratos Wistar
16.
Toxicol Sci ; 161(2): 421-430, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29069465

RESUMO

Ethylene glycol (EG) is a developmental toxicant in pregnant rats and mice. A suggested mechanism for this toxicity is that the EG metabolite, glycolic acid (GA), causes acidosis which may affect the embryonic heart rate (HR). This inhibition would cause periods of embryonic bradycardia and arrhythmia resulting in increased embryonic death and malformation in surviving embryos. This hypothesis was investigated using gestational day (GD) 11 and 13 rat embryos in vitro. Increasing concentrations of GA or lactic acid in the incubation medium caused a decrease in external pH (pHe) and a concentration-dependent decrease in embryonic HR. Increased concentrations of GA or lactic acid with pHe corrected to normal levels did not affect HR. Severely decreased pHe, caused by reduced NaHCO3 in the incubation medium, had little effect on the HR of GD 13 embryos but substantially reduced the HR of GD 11 embryos. These results suggest that increased monocarboxylate concentration (glycolate or lactate) needs to be in combination with increased H+ concentration (low pHe) to influence the embryonic HR. These results implicate the monocarboxylate transporter reported to be present in the early postnatal rat heart, the chick embryonic heart throughout development, and the chorioallantoic placenta. The results showed some evidence that the adverse effect of GA and reduced pHe on the embryonic HR increased with duration of exposure and hence lends support to the suggested mechanism of embryotoxicity for EG.


Assuntos
Acidose/induzido quimicamente , Desenvolvimento Embrionário/efeitos dos fármacos , Etilenoglicol/toxicidade , Glicolatos/toxicidade , Frequência Cardíaca/efeitos dos fármacos , Teratogênese/efeitos dos fármacos , Acidose/embriologia , Acidose/fisiopatologia , Animais , Meios de Cultura/química , Idade Gestacional , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Ratos , Ratos Sprague-Dawley
17.
Urolithiasis ; 46(5): 419-428, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29189886

RESUMO

Taraxasterol is one of the important constituents of Taraxacum officinale L. (Compositae) with antioxidant potential. The present study was designed to evaluate and compare the antiurolithiatic effects of taraxasterol and potassium citrate in the ethylene glycol induced urolithiatic rat. Urolithiasis was induced by ammonium chloride and ethylene glycol in adult male rats. Taraxasterol (2, 4 and 8 mg/kg) and potassium citrate (2.5 g/kg) were treated for 33 days by gavage. Then, the animals were anesthetized and weighted and blood, urine, liver and kidney sampling were done. The kidney sections were prepared by hematoxylin & eosin staining. The liver and kidney coefficients, urine pH, calcium, magnesium, oxalate and citrate levels, serum albumin, calcium and magnesium levels, serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, superoxide dismutase and glutathione peroxidase activities in serum, kidney and liver, number of calcium oxalate crystal deposits, score of crystal deposits, score of histopathological damages and score of inflammation in kidney sections were evaluated. The results showed that taraxasterol decreased liver and kidney coefficients (p < 0.001), serum calcium (p < 0.01) level, serum alanine aminotransferase (p < 0.001), aspartate aminotransferase (p < 0.001), lactate dehydrogenase (p < 0.05) activities, urine magnesium (p < 0.05) and oxalate (p < 0.001) levels, number of crystal deposits (p < 0.001), score of crystal deposits (p < 0.01), score of histopathological damages (p < 0.001) and score of inflammation (p < 0.01) in kidney sections, while increased urine pH (p < 0.01), calcium (p < 0.001) and citrate (p < 0.05), serum magnesium (p < 0.001) and albumin (p < 0.01) levels, superoxide dismutase and glutathione peroxidase in serum (p < 0.01), kidney (p < 0.05 and p < 0.001, respectively) and liver (p < 0.01 and p < 0.001, respectively) tissue homogenates in treated urolithiatic rats in comparison to the control urolithiatic rats. The effect of potassium citrate is the same as taraxasterol in treated urolithiatic rats. In conclusion, the effect of taraxasterol could be by improving liver function, changing serum and urine parameters, maintaining the antioxidant environment, reducing crystal deposition, excretion of small deposits from kidney and reducing the chance of them being retained in the urinary tract.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cálculos Renais/tratamento farmacológico , Eliminação Renal/efeitos dos fármacos , Esteróis/farmacologia , Triterpenos/farmacologia , Cloreto de Amônio/toxicidade , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Etilenoglicol/toxicidade , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Cálculos Renais/induzido quimicamente , Cálculos Renais/urina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Citrato de Potássio/farmacologia , Citrato de Potássio/uso terapêutico , Ratos , Ratos Wistar , Esteróis/uso terapêutico , Taraxacum/química , Resultado do Tratamento , Triterpenos/uso terapêutico
18.
Toxicol Mech Methods ; 28(3): 195-204, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28980857

RESUMO

Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500 mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.


Assuntos
Modelos Animais de Doenças , Doenças Transmitidas por Alimentos/etiologia , Hiperoxalúria/etiologia , Nefrocalcinose/etiologia , Ácido Oxálico/envenenamento , Folhas de Planta/efeitos adversos , Spinacia oleracea/efeitos adversos , Administração Oral , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Cristalização , Etilenoglicol/toxicidade , Doenças Transmitidas por Alimentos/metabolismo , Doenças Transmitidas por Alimentos/patologia , Doenças Transmitidas por Alimentos/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperoxalúria/metabolismo , Hiperoxalúria/patologia , Hiperoxalúria/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Nefrocalcinose/metabolismo , Nefrocalcinose/patologia , Nefrocalcinose/fisiopatologia , Ácido Oxálico/administração & dosagem , Ácido Oxálico/química , Ácido Oxálico/metabolismo , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Folhas de Planta/química , Ratos Wistar , Insuficiência Renal/etiologia , Spinacia oleracea/química
19.
Vet Ital ; 53(3): 251-254, 2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-29152707

RESUMO

Ethylene glycol (EG) is a well known toxic compound, the assumption of which can be fatal to pet animals as well as to humans. Limited information is available on the pathological features of EG poisoning in pet animals, with special emphasis on cats. Twenty-five cats with histologically confirmed EG intoxication were retrospectively investigated, in order to define more precisely the gross pathological findings and improve the diagnostic process. Furthermore, a brief comparison with the lesions reported in EG-poisoned human patients and dogs was also made.


Assuntos
Etilenoglicol/envenenamento , Animais , Gatos , Etilenoglicol/toxicidade , Humanos , Envenenamento/patologia , Estudos Retrospectivos
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