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1.
Curr Med Chem ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34382520

RESUMO

BACKGROUND: Cancer cells are usually recognized as foreign particles by the immune cells. Mounting evidences suggest important link between toll like receptors (TLRs) and carcinogenesis. This review article focused on the role of TLRs, especially TLR4 in breast cancer.

Methods: Research data on TLRs and cancer was explored in PubMed, Scopus, Google Scholar, and reviewed. Although some pioneer works are referenced, papers published in last ten years were mostly cited.

Results: TLRs are widely investigated pattern recognition receptors (PRR), and TLR4 is the most studied TLRs, implicated with occurrence of several types of cancers including breast cancer. TLR4 activation occurs via the binding of its ligand lipopolysaccharide (LPS), a component of the outer membrane of gram negative bacteria. Upon LPS binding, TLR4 dimerizes and recruits downstream signalling and/or adapter molecules leading to gene expression related to cancer cell proliferation, survival, invasion, and metastasis. Although LPS/TLR4 signalling seems a single signal transduction pathway, the TLR4 activation results in the activation of multiple diverse intracellular networks with huge cellular responses in both immune and cancer cells. The role of TLR4 in growth, invasion and metastasis of breast cancer is attracting huge attention in oncology research. Several clinical and preclinical studies utilize both TLR4 agonists and antagonists as treatment option for cancer therapy either as monotherapy or adjuvants for vaccine development.

Conclusion: This review narrates the role of LPS/TLR4 signalling in breast cancer development and future prospective for targeting LPS/TLR4 axis in the treatment of breast cancer.

2.
J Trace Elem Med Biol ; 68: 126804, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34111708

RESUMO

BACKGROUND: Knowledge of trace element stability during sample handling and preservation is a prerequisite to produce reliable test results in clinical trace element analysis. METHOD: An alkaline dissolution method has been developed using inductively coupled plasma mass spectrometry to quantify eighteen trace element concentrations: vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, bromine, molybdenum, cadmium, antimony, iodine, mercury, thallium, lead, and bismuth in human blood, using a small sample volume of 0.1 mL. The study evaluated the comparative effects of storage conditions on the stability of nutritionally essential and non-essential elements in human blood and plasma samples stored at three different temperatures (4 °C, -20 °C and -80 °C) over a one-year period, and analysed at multiple time points. The distribution of these elements between whole blood and plasma and their distribution relationships are illustrated using blood samples from 66 adult donors in Queensland. RESULTS: The refrigeration and freezing of blood and plasma specimens proved to be suitable storage conditions for many of the trace elements for periods up to six months, with essentially unchanged concentrations. Substantially consistent recoveries were obtained by preserving specimens at -20 °C for up to one year. Ultra-freezing of the specimens at -80 °C did not improve stability; but appeared to result in adsorption and/or precipitation of some elements, accompanied by a longer sample thawing time. A population sample study revealed significant differences between the blood and plasma concentrations of six essential elements and their relationships also varied significantly for different elements. CONCLUSION: Blood and plasma specimens can be reliably stored at 4 °C for six months or kept frozen at -20 °C up to one year to obtain high quality test results of trace elements.

3.
J Anal Toxicol ; 44(9): 1036-1046, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32232355

RESUMO

Essential and nonessential element concentrations in human blood provide important information on the nutritional status of individuals and can assist in the screening or diagnosis of certain disorders and their association with other causative factors. A simple and sensitive method, suitable for use with small sample volumes, for quantification of multiple trace element concentrations in whole blood and plasma has been developed using inductively coupled plasma-mass spectrometry. Method validation was performed using standard reference materials of whole blood and serum using varying sample treatments with nitric acid, water and hydrogen peroxide. The method was applied to quantify the trace element concentrations in whole blood and plasma samples (0.1 mL) from 50 adult blood donors in Queensland. The whole blood sample (5 mL) was collected in Vacutainer tubes with K2EDTA as anticoagulant. The developed method was able to quantify, in blood and plasma samples over a wide range of concentrations, several essential elements: cobalt, copper, zinc, iron, manganese and selenium; the nutritionally probably essential elements vanadium and strontium; and nonessential elements including lead, cadmium, arsenic, caesium, barium, thallium and uranium. Significant differences (P < 0.0001) were observed between whole blood and plasma concentrations for 13 elements; 5 of the measured elements, cobalt (0.49 vs. 0.36 µg/L), copper (1.0 vs. 0.75 mg/L), strontium (28 vs. 16 µg/L), barium (1.5 vs. 0.64 µg/L) and thallium (0.06 vs. 0.03 µg/L), had higher mean concentrations in plasma than in blood. Whole blood concentrations of nine trace elements were significantly correlated (P < 0.0001) with plasma concentrations. The distribution of the trace elements between human blood and plasma varied considerably for the different elements. These results indicate that, using a small sample volume, this assay is suitable for the evaluation of nutritional status as well as in monitoring human toxic elemental exposures.


Assuntos
Espectrometria de Massas , Oligoelementos/sangue , Adulto , Cádmio , Cobre , Humanos , Plasma , Selênio , Análise Espectral , Zinco
4.
J Food Biochem ; 43(8): e12958, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31368558

RESUMO

The study reports the phenolic composition of propolis from Bangladesh and its ameliorative effects against tetracycline-induced hepatonephrotoxicity in rats. Male Wistar Albino rats (n = 18) were randomly divided into three following groups: (1) normal control, (2) tetracycline-treatment (200 mg kg-1  rat-1 ), and (3) tetracycline (200 mg kg-1  rat-1 ) + propolis (100 mg kg-1  rat-1 ) treatments. The ethanolic extract of propolis contained major phenolic acids as well as a flavonoid, rutin. Oral exposure to tetracycline caused severe hepatic and renal damage as indicated by significant alterations in liver marker enzymes in rat serum: bilirubin and protein concentrations, lipid profile, and markers of kidney function when compared with controls. The observed biochemical perturbations were accompanied by histopathological changes. Co-administration with propolis extract, however, prevented the changes in biochemical parameters, as revealed by maintenance of cell membrane integrity and regulation of lipid profile and the conservation of the histoarchitecture. PRACTICAL APPLICATIONS: Propolis is a resinous honeybee product which is becoming increasingly popular due to its potential contributions to human health. The phenolic compounds identified in propolis from Bangladesh were effective against tetracycline-induced hepatic and renal toxicity. Propolis may be a promising natural product in reducing the effects of chronic liver and kidney damage.


Assuntos
Nefropatias/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Própole/química , Tetraciclina/efeitos adversos , Animais , Bangladesh , Abelhas , Bilirrubina/sangue , Humanos , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/fisiopatologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/lesões , Fígado/metabolismo , Hepatopatias/sangue , Hepatopatias/etiologia , Testes de Função Hepática , Masculino , Estresse Oxidativo/efeitos dos fármacos , Própole/administração & dosagem , Ratos , Ratos Wistar
5.
J Toxicol ; 2019: 2529569, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281355

RESUMO

The aim of this study was to investigate the antioxidant potentials, subacute toxicity, and beneficiary effects of methanolic extract of pomelo (Citrus grandis L. Osbeck) in rats. Long Evans rats were divided into four groups of eight animals each. The rats were orally treated with three doses of pomelo (250, 500, and 1000 mg/kg) once daily for 21 days. Pomelo extract contained high concentrations of polyphenols, flavonoids, and ascorbic acid while exhibiting high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and ferric reducing antioxidant power values. There was no significant change in the body weight, percentage water content, and relative organ weight at any administered doses. In addition, no significant alterations in the hematological parameters were also observed. However, rats which received 1000 mg/kg dose had a significant reduction in some serum parameters, including alanine transaminase (15.29%), alkaline phosphatase (2.5%), lactate dehydrogenase (15.5%), γ-glutamyltransferase (20%), creatinine (14.47%), urea (18.50%), uric acid (27.14%), total cholesterol (5.78%), triglyceride (21.44%), low-density lipoprotein cholesterol (40.74%), glucose (2.48%), and all atherogenic indices including cardiac risk ratio (24.30%), Castelli's risk index-2 (45.71%), atherogenic coefficient (42%), and atherogenic index of plasma (25%) compared to control. In addition, the highest dose (1000 mg/kg) caused a significant increase in iron (12.07%) and high-density lipoprotein cholesterol (8.87%) levels. Histopathological findings of the vital organs did not indicate any pathological changes indicating that pomelo is nontoxic, safe, and serves as an important source of natural antioxidants. In addition, the fruit extract has the potential to ameliorate hepato- and nephrotoxicities and cardiovascular diseases as well as iron deficiency anemia.

6.
Chem Res Toxicol ; 32(8): 1619-1629, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31334637

RESUMO

The aim of the present study was to evaluate the protective effect of Syzygium cymosum leaf methanol extract (SCL) against carbofuran (CF)-induced hepatotoxicity in Sprague-Dawley rats, along with the identification and quantification of polyphenolic composition by high-performance liquid chromatography (HPLC). Results revealed the presence of alkaloids, tannins, and flavonoids in SCL. Similarly, HPLC analysis suggests that SCL contains some known important antioxidants, such as rutin, benzoic acid, and salicylic acid that could be responsible for the hepatoprotective activity of the extract. In CF-exposed rats, significant hematological alterations along with histological changes were marked by the presence of necrosis, congestion, and inflammation. CF-intoxication also showed an increase in lipid peroxidation and decrease in cellular antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) levels in rats compared with the control group. Furthermore, coadministration of SCL significantly ameliorated the abnormalities and improved the cellular arrangement in experimental animals. SCL also reversed the alteration of hematological and biochemical parameters and brought them back to normal levels as compared to the control group. In conclusion, S. cymosum may be one of the best sources of natural antioxidant compounds that can be used in the treatment of oxidative stress and stress-related diseases and disorders.


Assuntos
Antioxidantes/farmacologia , Carbofurano/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Eritrócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Syzygium/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Ratos , Ratos Sprague-Dawley
7.
Artigo em Inglês | MEDLINE | ID: mdl-29861774

RESUMO

The current study aimed to investigate the ameliorative effects of two types of mushrooms, Ganoderma lucidum (GL) and Auricularia polytricha (AP), against carbofuran- (CF) induced toxicity in rats. Male Wistar rats (n = 42) were divided into six equal groups. The rats in the negative control group received oral administration of CF at 1 mg/kg with the normal diet for 28 days. The treatment groups received oral administration of ethanolic extract of GL or AP at 100 mg/kg followed by coadministration of CF at 1 mg/kg with the normal diet for the same experimental period, respectively. In the CF alone treated group, there were significant decreases in the erythrocytic and thrombocytic indices but increases in the concentrations of the total leukocytes, including the agranulocytes. A significant increase in all of the liver function biomarkers except albumin, in lipid profiles except high-density lipoprotein, and in the kidney function markers occurred in the negative control group compared to the rats of the normal control and positive control groups. The coadministration of mushroom extracts significantly ameliorated the toxic effects of the CF. The GL mushroom extract was more efficacious than that of the AP mushroom, possibly due to the presence of high levels of phenolic compounds and other antioxidants in the GL mushroom.

8.
Artigo em Inglês | MEDLINE | ID: mdl-29234381

RESUMO

The antihyperglycemic, antidiabetic, and antioxidant potentials of the methanolic extract of Garcinia pedunculata (GP) fruit in rats were investigated. The acute antihyperglycemic effect of different doses of GP was studied in normal male Wistar rats. Diabetes was induced by streptozotocin (STZ) injection in another cohort of male Wistar rats and they showed significantly higher blood glucose and glycated hemoglobin (HbA1c) levels, altered lipid profiles, and lower insulin levels compared to nondiabetic control animals. There were increased lipid peroxidation and reduced levels of cellular antioxidant enzymes in different tissues of diabetic rats. However, oral administration of GP extracts, especially the highest dose (1000 mg/kg), significantly ameliorated hyperglycemia (42%); elevated insulin levels (165%); decreased HbA1c (29.4%); restored lipid levels (reduction in TG by 25%, TC by 15%, and LDL-C by 75% and increase in HDL-C by 4%), liver and renal function markers, and lipid peroxidation (reduction by 52% in the liver, 39% in the kidney, 44% in the heart, and 46% in the pancreas); and stimulated tissue antioxidant enzymes to near normalcy. Overall, the findings suggest that GP fruit is effective against hyperglycemia and could be used in the treatment of diabetes and its complications and other oxidative stress-mediated pathological conditions.

9.
Biomed Pharmacother ; 94: 256-264, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28763749

RESUMO

Increases in the incidence of cardiovascular disease (CVD) have aroused strong interest in identifying antioxidants from natural sources for use in preventive medicine. Citrus macroptera (C. macroptera), commonly known as "Satkara", is an important herbal and medicinal plant reputed for its antioxidant, nutritious and therapeutic uses. The aim of the present study was to investigate the cardio-protective effects of ethanol extracts of C. macroptera peel and pulp against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats (n=36) were pre-treated with peel and pulp extracts (500mg/kg) for 45days. They received a challenge with ISO (85mg/kg) on the 44th and 45th days. Our findings indicated that subcutaneous injection of ISO induced severe myocardial injuries associated with oxidative stress, as confirmed by elevated lipid peroxidation (LPO) and decreased cellular reduced glutathione (GSH) and anti-peroxidative enzymes, including glutathione peroxidase, glutathione reductase and glutathione-S-transferase, compared with levels observed in control animals. Pre-treatment with C. macroptera peel and pulp extracts prior to ISO administration however, significantly improved many of the investigated biochemical parameters, i.e., cardiac troponin I, cardiac marker enzymes, lipid profile and oxidative stress markers. The fruit peel extract showed stronger cardio-protective effects than the pulp extract. The biochemical findings were further confirmed by histopathological examinations. Overall, the increased endogenous antioxidant enzyme activity against heightened oxidative stress in the myocardium is strongly suggestive of the cardio-protective potential of C. macroptera.


Assuntos
Cardiotônicos/uso terapêutico , Citrus/química , Isoproterenol/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/metabolismo , Cardiotônicos/isolamento & purificação , Modelos Animais de Doenças , Frutas/química , Masculino , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Ratos Wistar
10.
Pharm Biol ; 55(1): 1937-1945, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28675957

RESUMO

CONTEXT: Turmeric (Curcuma longa L. [Zingiberaceae]) is used in the treatment of a variety of conditions including pesticide-induced toxicity. OBJECTIVE: The study reports the antioxidant properties and the protective effects of turmeric against carbofuran (CF)-induced toxicity in rats. MATERIALS AND METHODS: The antioxidant potential was determined by using free radicals scavenging activity and ferric reducing antioxidant power values. Male Wistar rats were randomly divided into four groups, designated as control, turmeric (100 mg/kg/day), CF (1 mg/kg/day) and turmeric (100 mg/kg/day) + CF (1 mg/kg/day) treatments. All of the doses were administered orally for 28 consecutive days. The biological activity of the turmeric and CF was determined by using several standard biochemical methods. RESULTS: Turmeric contains high concentrations of polyphenols (8.97 ± 0.15 g GAEs), flavonoids (5.46 ± 0.29 g CEs), ascorbic acid (0.06 ± 0.00 mg AEs) and FRAP value (1972.66 ± 104.78 µM Fe2+) per 100 g of sample. Oral administration of CF caused significant changes in some of the blood indices, such as, mean corpuscular volume, corpuscular hemoglobin, white blood cell, platelet distribution width and induced severe hepatic injuries associated with oxidative stress, as observed by the significantly higher lipid peroxidation (LPO) levels when compared to control, while the activities of cellular antioxidant enzymes (including superoxide dismutase and glutathione peroxidase) were significantly suppressed in the liver tissue. DISCUSSION AND CONCLUSION: Turmeric supplementation could protect against CF-induced hematological perturbations and hepatic injuries in rats, plausibly by the up-regulation of antioxidant enzymes and inhibition of LPO to confer the protective effect.


Assuntos
Células Sanguíneas/efeitos dos fármacos , Carbofurano/toxicidade , Curcuma , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Células Sanguíneas/metabolismo , Células Sanguíneas/patologia , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Leucócitos/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Extratos Vegetais/isolamento & purificação , Distribuição Aleatória , Ratos , Ratos Wistar
11.
Artigo em Inglês | MEDLINE | ID: mdl-28243309

RESUMO

This study was undertaken to investigate the toxicological profile of a methanolic extract of Garcinia pedunculata fruit in rats by conducting hematological, biochemical, and histopathological examinations. Long Evans rats were divided into four groups, each with 6 animals, and were treated with three oral doses (250, 500, and 1000 mg/kg) once daily for 21 days. The extract did not cause significant changes in body and relative organ weight, percent water content, or hematological parameters at any administered doses. However, a significant dose-dependent positive effect in serum lipid profile and all atherogenic indices including the cardiac risk ratio, Castelli's risk index-2, and the atherogenic coefficient were observed. Significant increases in the levels of iron and decreases in serum alkaline phosphatase, alanine transaminase, and lactate dehydrogenase activities and the levels of serum glucose were noted when the extract was administered at the highest dose (1000 mg/kg). Histopathological examination of the target tissues further confirmed that the extract was safe and had no observed toxicological features. Our study indicates that G. pedunculata fruit is nontoxic, has the potential to be effective against atherosclerosis, and may be used as a hepatoprotectant. The fruit extract is also beneficial to those with iron deficiency and hyperglycemia.

12.
Artigo em Inglês | MEDLINE | ID: mdl-28261310

RESUMO

Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP) has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO-) induced myocardial infarction in rats. Male Wistar rats (n = 32) were pretreated orally with an ethanol extract of MP (100 mg/kg/day) for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

13.
Biomed Res Int ; 2016: 6437641, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27294126

RESUMO

The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium.


Assuntos
Mel , Isoproterenol/efeitos adversos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/prevenção & controle , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Aspartato Aminotransferases/metabolismo , Peso Corporal , Creatina Quinase Forma MB/metabolismo , Radicais Livres , L-Lactato Desidrogenase/metabolismo , Masculino , Miocárdio/enzimologia , Estresse Oxidativo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Troponina I/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-27034701

RESUMO

Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

15.
Hum Exp Toxicol ; 35(9): 991-1004, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26519480

RESUMO

This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.


Assuntos
Clorpirifos/toxicidade , Poluentes Ambientais/toxicidade , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Clorpirifos/farmacocinética , Poluentes Ambientais/farmacocinética , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Rim/metabolismo , Testes de Função Renal , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Testes de Função Hepática , Ratos Wistar , Distribuição Tecidual
16.
Biomed Res Int ; 2015: 624159, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26539517

RESUMO

We investigated the protective role of Withania somnifera leaf extract (WSLEt) on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. Subcutaneous injection of ISO (85 mg/kg body weight (b.w.)) administered to rats for two consecutive days caused a significant increase in cardiac troponin I (cTnI) levels and serum lipid profiles, as well as the activities of some marker enzymes. In addition to these diagnostic markers, there were increased levels of lipid peroxidation (LPO) and decreased activities of enzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), and glutathione-S-transferase (GST)) in the myocardium. However, oral pretreatment (100 mg/kg b.w.) with WSLEt for 4 weeks elicited a significant cardioprotective activity by lowering the levels of cTnI, lipid profiles, and marker enzymes. The levels of LPO products were also significantly decreased. Elevated activities of antioxidant enzymes were also observed in rats pretreated with WSLEt. As further confirmed histopathologically, our findings strongly suggest that the cardioprotective effect of WSLEt on myocardium experiencing ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidant system and an inhibition of LPO in the myocardial membrane. We conclude that WSLEt confers some protection against oxidative damage in ISO-induced MI in rats.


Assuntos
Antioxidantes/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/química , Biomarcadores/sangue , Glutationa Peroxidase/sangue , Humanos , Isoproterenol/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/patologia , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Superóxido Dismutase/sangue , Troponina I/sangue , Withania/química
17.
Biomed Res Int ; 2015: 286051, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064893

RESUMO

The present study was designed to investigate the cardioprotective effects of Malaysian Tualang honey against isoproterenol- (ISO-) induced myocardial infarction (MI) in rats by investigating changes in the levels of cardiac marker enzymes, cardiac troponin I (cTnI), triglycerides (TG), total cholesterol (TC), lipid peroxidation (LPO) products, and antioxidant defense system combined with histopathological examination. Male albino Wistar rats (n = 40) were pretreated orally with Tualang honey (3 g/kg/day) for 45 days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and aspartate transaminase (AST)), cTnI, serum TC, and TG levels. In addition, ISO-induced myocardial injury was confirmed by a significant increase in heart lipid peroxidation (LPO) products (TBARS) and a significant decrease in antioxidant enzymes (SOD, GPx, GRx, and GST). Pretreatment of ischemic rats with Tualang honey conferred significant protective effects on all of the investigated biochemical parameters. The biochemical findings were further confirmed by histopathological examination in both Tualang-honey-pretreated and ISO-treated hearts. The present study demonstrates that Tualang honey confers cardioprotective effects on ISO-induced oxidative stress by contributing to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.


Assuntos
Antioxidantes/metabolismo , Mel , Infarto do Miocárdio/sangue , Infarto do Miocárdio/prevenção & controle , Miocárdio/enzimologia , Animais , Aspartato Aminotransferases/sangue , Cardiotônicos/administração & dosagem , Colesterol/sangue , Creatina Quinase Forma MB/sangue , Humanos , Isoproterenol/toxicidade , L-Lactato Desidrogenase/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Ratos , Triglicerídeos/sangue , Troponina I/sangue
18.
Artigo em Inglês | MEDLINE | ID: mdl-25530774

RESUMO

Honey, a supersaturated natural product of honey bees, contains complex compounds with antioxidant properties and therefore has a wide a range of applications in both traditional and modern medicine. In the present study, the protective effects of Sundarban honey from Bangladesh against acetaminophen- (APAP-) induced hepatotoxicity and nephrotoxicity in experimental rats were investigated. Adult male Wistar rats were pretreated with honey (5 g/kg) for 4 weeks, followed by the induction of hepatotoxicity and nephrotoxicity via the oral administration of a single dose of APAP (2 g/kg). Organ damage was confirmed by measuring the elevation of serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total protein (TP), total bilirubin (TB), urea, creatinine, and malondialdehyde (MDA). Histopathological alterations observed in the livers and the kidneys further confirmed oxidative damage to these tissues. Animals pretreated with Sundarban honey showed significantly markedly reduced levels of all of the investigated parameters. In addition, Sundarban honey ameliorated the altered hepatic and renal morphology in APAP-treated rats. Overall, our findings indicate that Sundarban honey protects against APAP-induced acute hepatic and renal damage, which could be attributed to the honey's antioxidant properties.

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