Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 23
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Chemosphere ; 287(Pt 3): 132245, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34543908

RESUMO

Aluminum phosphide is a well-known hazardous agent used as an agricultural pesticide to protect stored grains from insect damage. However, accidental consumption of a trivial amount of it caused irreversible damage to the human body or even death in acute cases. The present study used taurine and grape seed extract as a natural cardioprotective medicine against aluminum phosphide poisoning by decreasing oxidative stress. The activity of oxidative stress biomarkers (Malondialdehyde, Catalase, Protein carbonyl, and Superoxide dismutase) were evaluated in the cell line model on Human Cardiac Myocyte cells. In the beginning, to clarify the pure impact of aluminum phosphide poison, taurine, and grape seed extract on the human heart cells, their effects on the biomarkers quantity in cell line were measured. Subsequently, the effect of taurine and grape seed extract with various concentrations as a treatment on the oxidative stress biomarkers of the poisoned heart cells were studied. Data analysis reveals that taurine and grape seed extract treatment can successfully diminish the poisoning effect by their antioxidant properties. The oxidative markers values of the poisoned cells were recovered by taurine and grape seed extracts treatment. Taurine (2 g/l) can recover Malondialdehyde, Catalase, Protein carbonyl, and Superoxide dismutase by 56%, 78%, 88%, 78%, when the recovering power of grape seed extract (100 g/l) for the aforementioned enzymes are 56%, 0.71%,74%, 51%, respectively. Therefore, it is clear that the performance of taurine in the recovery of the biomarkers' value is better than grape seed extract.


Assuntos
Extrato de Sementes de Uva , Praguicidas , Vitis , Compostos de Alumínio , Antioxidantes , Biomarcadores , Extrato de Sementes de Uva/farmacologia , Humanos , Estresse Oxidativo , Fosfinas , Taurina/farmacologia
2.
Int J Pharm ; 610: 121208, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34673162

RESUMO

Rutin is a natural antioxidant compound with several therapeutic benefits. However, the application of this bioactive compound is limited due to its low stability and bioavailability. To overcome these limitations, this study aimed to encapsulate rutin into nanophytosomes (NPs) and evaluate the therapeutic potency of this nanocarrier in streptozotocin (STZ)-induced diabetic rats. The particle size, zeta potential, and encapsulation efficiency of the prepared NPs were 72.72 nm, -22 mV, and 93.7%, respectively. The in vivo study showed that the oral administration of rutin-loaded NPs (containing 25 mg rutin/kg per day) for 4 weeks was more effective than free rutin in the control of hyperglycemia and hyperlipidemia in the STZ-induced diabetic rats. Additionally, the administration of rutin-loaded NPs regulated the activities of liver marker enzymes and the levels of total hemoglobin and glycated hemoglobin in the diabetic rats. The antioxidant defenses in the diabetic rats were increased by the administration of rutin-loaded NPs more than free rutin. Moreover, the histopathological study showed that the administration of rutin-loaded NPs restored the diabetes-induced damages in kidney, liver, and pancreas. In conclusion, encapsulation of rutin with phytosomes is an effective technique to benefit from its therapeutic potential, especially to attenuate diabetic complications.

3.
Food Chem Toxicol ; 154: 112347, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34139304

RESUMO

BACKGROUND: Aluminum phosphide (AlP) causes severe cardiotoxicity. Taurine has been chosen for the present study because of its positive known effects on cardiac injuries. METHOD: To evaluate AlP-induced cardiotoxicity, the animals were divided into seven groups, including the control group, the taurine group (500 mg/kg), AlP with LD50 dose, AlP + taurine 20, 50, 100, and 200 mg/kg group. To assess cardiac hemodynamic parameters, Wistar rats received taurine intraperitoneally 60 min after AlP gavage. Cardiac hemodynamic parameters were evaluated for 180 min. To study biochemical parameters, 24 h after AlP treatment, the animals were sacrificed, and heart tissues were collected. RESULT: ECG, BP, and HR abnormalities of AlP poisoning were improved by taurine treatment. AlP induced biochemical alterations including complexes I and IV activities, the ADP/ATP ratio, mitochondrial membrane potential, cytochrome C release, and oxidative stress biomarkers ameliorated by taurine. Moreover, taurine improved apoptosis, as well as lessened CK-MB and troponin I levels. Also, there were no significant changes between taurine 500 mg/kg and the control group in tests. CONCLUSION: The present findings showed that taurine could be a possible candidate for AlP cardiotoxicity treatment via the effect on mitochondrial electron transfer chain and maintaining intracellular ATP balance.


Assuntos
Compostos de Alumínio/toxicidade , Cardiotônicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Fosfinas/toxicidade , Taurina/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiotoxicidade/metabolismo , Creatina Quinase/metabolismo , Eletrocardiografia/efeitos dos fármacos , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Miocárdio/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Troponina I/metabolismo
4.
J Pharm Pharmacol ; 73(11): 1539-1546, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33793778

RESUMO

OBJECTIVES: The effects of Crocin as a cardioprotective material against Aluminum phosphide poisoning by reducing the oxidative stress is investigated. METHODS: The level of biomarkers of oxidative stress (Catalase, Superoxide dismutase, Malondialdehyde and Protein carbonyl) were measured in the cell culture model on Human Cardiac Myocyte cells to detect the protective effect of crocin. Initially, to define the pure impact of aluminum phosphide poison and crocin on the heart cells, their effects on the biomarkers quantity in cell line were measured, separately, using the standard related kits. Later the effect of crocin with different concentration as a treatment on the oxidative stress biomarkers of the poisoned heart cells were monitored. Note that in pre-treatment case, the crocin was initially added to the cells before poisoning them. Data were analyzed using the analysis of variance method. KEY FINDINGS: Results showed that crocin treatment reduced the aluminum phosphide (AlP) poisoning effect significantly. The treatment resulted in substantial deviation in the biomarkers of oxidative stress at the pre- and post-treatment phases for all groups. The oxidative markers values of the poisoned cells were recovered by crocin treatment. CONCLUSIONS: Crocin is proposed as a potentially powerful antioxidant to treat the cardiotoxicity caused by aluminum phosphide poisoning.

5.
J Pept Sci ; 27(3): e3292, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33200451

RESUMO

To investigate whether peptide sequences with specific translocation across the gastrointestinal barrier can be identified as drug delivery vehicles, in vivo phage display was conducted. For this purpose, a random library of 12-mer peptides displayed on M13 bacteriophage was orally administered to mice followed by recovery of the phage particles from the blood samples after three consecutive biopanning rounds. The obtained peptide sequences were analyzed using bioinformatics tools and software. The results demonstrated that M13 bacteriophage bearing peptides translocate nonspecifically across the mice intestinal mucosal barrier deduced from random distribution of amino acids in different positions of the identified peptide sequences. The most probable reason for entering the phage particles into systemic circulation after oral administration of the peptide library can be related to the nanoscale nature of their structures which provides a satisfying platform for the purpose of designing nanocarriers in pharmaceutical applications.


Assuntos
Bacteriófago M13/metabolismo , Mucosa Intestinal/metabolismo , Peptídeos/metabolismo , Administração Oral , Animais , Sistemas de Liberação de Medicamentos , Mucosa Intestinal/virologia , Masculino , Camundongos , Biblioteca de Peptídeos , Peptídeos/administração & dosagem
6.
Iran J Pharm Res ; 17(4): 1465-1475, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568704

RESUMO

Thioridazine (TZ) is used mainly in the treatment of schizophrenia. However, hepatotoxicity as a life-threatening adverse effect is associated with its clinical use. In this context, we examined the cytotoxic mechanisms of TZ on freshly isolated rat hepatocytes to better understanding of the pathogenesis of TZ-induced hepatotoxicity. Hepatocytes were prepared by the method of collagenase enzyme perfusion via the portal vein. The level of parameters such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosomal membrane integrity and cellular glutathione (GSH) content in TZ-treated and non-treated hepatocytes were determined and the mentioned markers were assessed in the presence of Coenzyme Q10 and/or melatonin. Results showed that TZ caused an increase in ROS formation as well as induction of LPO and GSH depletion. Moreover, mitochondria and lysosomes seem to be targets of TZ-induced toxicity. The administration of Coenzyme Q10 and/or melatonin efficiently decreased the rate of ROS formation, LPO and improved cell viability, MMP, GSH level and lysosome membrane integrity. This study proposes the possible protective role of Coenzyme Q10 and/or melatonin against TZ-induced cellular injury probably through their radical scavenging properties and their effects on mitochondria and lysosomes.

7.
Adv Pharm Bull ; 6(3): 423-433, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27766227

RESUMO

Purpose: The aim of the present study was to determine the ability of grape seed extract (GSE) as a powerful antioxidant in preventing adverse effect of doxorubicin (DOX) on heart function. Methods: Male rats were divided into three groups: control, DOX (2 mg/kg/48h, for 12 days) and GSE (100 mg/kg/24h, for 16 days) plus DOX. Left ventricular (LV) function and hemodynamic parameters were assessed using echocardiography, electrocardiography and a Millar pressure catheter. Histopathological analysis and in vitro antitumor activity were also evaluated. Results: DOX induced heart damage in rats through decreasing the left ventricular systolic and diastolic pressures, rate of rise/decrease of LV pressure, ejection fraction, fractional shortening and contractility index as demonstrated by echocardiography, electrocardiography and hemodynamic parameters relative to control group. Our data demonstrated that GSE treatment markedly attenuated DOX-induced toxicity, structural changes in myocardium and improved ventricular function. Additionally, GSE did not intervene with the antitumor effect of DOX. Conclusion: Collectively, the results suggest that GSE is potentially protective against DOX-induced toxicity in rat heart and maybe increase therapeutic index of DOX in human cancer treatment.

8.
Turk J Med Sci ; 46(4): 1223-32, 2016 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-27513429

RESUMO

BACKGROUND/AIM: Almond hull is produced in high amounts and mostly used as livestock feed. This study was designed to examine the impact of almond hull powder (AHP) administration on lipid profile and antioxidant activities in plasma and liver in hyperlipidemic rats. MATERIALS AND METHODS: As the first step, the antioxidant capacity and radical scavenging activity of AHP were determined using calorimetric methods. Then 36 adult male Wistar rats were randomly divided into 6 groups: group 1 with oral administration of 10% AHP, group 2 with oral administration of 20% AHP, group 3 with oral administration of 30% AHP, group 4 as a positive control with a high cholesterol diet, group 5 as a negative control with a normal diet, and group 6 as a sham group with a normal diet and 20% AHP. The rats were fed a hypercholesterolemic diet to create a hyperlipidemia rat model and then they received AHP for 30 days. RESULTS: Antioxidant and radical scavenging activity of the AHP extract showed a high content of antioxidants that exert potent radical scavenging activity. According to the results obtained, upon the administration of AHP the levels of cholesterol and triglycerides significantly decreased, while the antioxidant capacity of plasma increased. CONCLUSION: AHP with bioactive compounds and fiber can reduce total cholesterol and triglycerides and improve serum antioxidant capacity.


Assuntos
Prunus dulcis , Animais , Antioxidantes , Hiperlipidemias , Lipídeos , Fígado , Masculino , Extratos Vegetais , Ratos , Ratos Wistar
9.
Toxicol Mech Methods ; 26(7): 520-528, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27387968

RESUMO

The hepatotoxic effects of the antipsychotic agent, risperidone (RIS) were investigated for better understanding the pathogenesis of RIS in liver toxicity in vivo and in in vitro. Isolated rat hepatocytes were obtained by collagenase perfusion technique and were then incubated with RIS, different antioxidants in particular coenzyme Q10 (CoQ10), N-acetyl cysteine (NAC). Our results showed that RIS could induce cytotoxicity via rising reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation. All of these effects were significantly (p < 0.05) inhibited by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate (ATP) generators. Similar outcomes were obtained from the in vivo experiments. Liver function enzyme test and histopathological evaluation confirmed RIS-(6 mg/kg) induced damage. Based on these results, it is suggested that RIS-induced liver toxicity is associated with mitochondrial/lysosomal cross-talk following the initiation of oxidative stress. Thus, the use of CoQ10 and/or NAC seems to be a safe therapeutic option in this context.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Risperidona/toxicidade , Ubiquinona/análogos & derivados , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ubiquinona/farmacologia
10.
Life Sci ; 157: 145-151, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27297631

RESUMO

Doxorubicin (DOX)-induced cardiotoxicity is well-known as a serious complication of chemotherapy in patients with cancer. It is unknown whether crocin (CRO), main component of Crocus sativus L. (Saffron), could reduce the severity of DOX-induced cardiotoxicity. Therefore, this study was undertaken to assess the protective impact of CRO on DOX-induced cardiotoxicity in rats. The rats were divided into four groups: control, DOX (2mg/kg/48h, for 12days), and CRO groups that receiving DOX as in group 2 and CRO (20 and 40mg/kg/24h, for 20days) starting 4days prior to first DOX injection and throughout the study. Echocardiographic, electrocardiographic and hemodynamic studies, along with histopathological examination and MTT test were carried out. Our findings demonstrate that DOX resulted in cardiotoxicity manifested by decreased the left ventricular (LV) systolic and diastolic pressures, rate of rise/drop of LV pressure, ejection fraction, fractional shortening and contractility index, as compared to control group. In addition, histopathological analysis of heart confirmed adverse structural changes in myocardial cells following DOX administration. The results also showed that CRO treatment significantly improved DOX-induced heart damage, structural changes in the myocardium and ventricular function. In addition, CRO did not affect the in vitro antitumor activity of DOX. Taken together, our data confirm that CRO is protective against cardiovascular-related disorders produced by DOX, and clinical studies are needed to examine these findings in human.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Carotenoides/uso terapêutico , Doxorrubicina/toxicidade , Coração/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Wistar
11.
Life Sci ; 145: 190-204, 2016 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-26731041

RESUMO

Rat aorta assay provides a low cost and rapid platform, especially for preclinical in vivo models. The signaling pathways of the analog on the vessels could be evaluated separately on the endothelium or smooth muscle cells by rings of the rat aorta in vitro. The rat aorta is used for angiogenesis modeling to integrate the benefits of the both in vivo and in vitro models. These explain the importance and usage of rat aorta in researches. Furthermore, about 4503 articles have been published with the key word "rat aorta" in title or abstract from 1955 until the end of 2013 in Medline. In this review, these articles were organized into two main categories: in vivo and in vitro studies. The in vitro section focused on the rat aorta model, as a tool for evaluate the mechanism of vasodilation, vasoconstriction and angiogenesis. In the in vivo section, the most important usage of this tissue was evaluated. Also, the vasotonic signaling pathways in the vessel are explained briefly and some rat aorta applications in vitro and in vivo have been discussed.


Assuntos
Aorta/efeitos dos fármacos , Aorta/fisiologia , Avaliação Pré-Clínica de Medicamentos/métodos , Ratos/fisiologia , Animais , Aorta/anatomia & histologia , Aorta/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Ratos/anatomia & histologia , Transdução de Sinais/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
12.
Xenobiotica ; 46(4): 369-78, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26364812

RESUMO

1. Olanzapine (OLZ) is a widely used atypical antipsychotic agent for the treatment of schizophrenia and other disorders. Serious hepatotoxicity and elevated liver enzymes have been reported in patients receiving OLZ. However, the cellular and molecular mechanisms of the OLZ hepatotoxicity are unknown. 2. In this study, the cytotoxic effect of OLZ on freshly isolated rat hepatocytes was assessed. Our results showed that the cytotoxicity of OLZ in hepatocytes is mediated by overproduction of reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation preceding cell lysis. All the aforementioned OLZ-induced cellular events were significantly (p < 0.05) prevented by ROS scavengers, antioxidants, endocytosis inhibitors and adenosine triphosphate generators. Also, the present results demonstrated that CYP450 is involved in OLZ-induced oxidative stress and cytotoxicity mechanism. 3. It is concluded that OLZ hepatotoxicity is associated with both mitochondrial/lysosomal involvement following the initiation of oxidative stress in hepatocytes.


Assuntos
Benzodiazepinas/farmacologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/metabolismo , Morte Celular/efeitos dos fármacos , Separação Celular , Inibidores das Enzimas do Citocromo P-450/farmacologia , Dissulfeto de Glutationa/metabolismo , Hepatócitos/efeitos dos fármacos , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade Mitocondrial , Olanzapina , Fenobarbital , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
13.
J Cardiovasc Pharmacol ; 67(3): 237-45, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26544684

RESUMO

Doxorubicin (DOX) is an effective anticancer agent, but adverse cardiotoxic effects limit its use. Compounds reducing DOX cardiotoxicity could improve its therapeutic index. This study investigated the protective effects of phenytoin (Phen) for DOX-induced cardiomyopathy. Male Wistar rats were randomized into 5 groups to receive either saline, DOX (2 mg/kg per 48 hours, 6 doses, intraperitoneally) or DOX + Phen (5, 10, or 20 mg/kg/d, starting 4 days before DOX, intraperitoneally). The animals were assessed 24 hours after the last injection. Left ventricular (LV) function and hemodynamic parameters were assessed using transthoracic echocardiography, electrocardiography, and a Millar pressure catheter. Histopathological studies were performed, and the effect of Phen on the cytotoxicity of DOX was evaluated in vitro for the human breast adenocarcinoma cell line. DOX-impaired LV function significantly decreased the LV systolic and diastolic pressures, rate of rise/decrease of LV pressure, ejection fraction, fractional shortening, and contractility index. DOX caused structural changes in myocardial cells. Treatment with Phen decreased DOX-induced toxicity, significantly improved ventricular function, and ameliorated structural changes in the myocardium. Phen also did not interfere with the antitumor effect of DOX. The results confirm the cardioprotective effect of Phen against DOX-induced cardiomyopathy without removing antitumor effect of DOX.


Assuntos
Cardiomiopatias/prevenção & controle , Doxorrubicina , Ventrículos do Coração/efeitos dos fármacos , Fenitoína/farmacologia , Substâncias Protetoras/farmacologia , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Cardiotoxicidade , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Células MCF-7 , Masculino , Contração Miocárdica/efeitos dos fármacos , Ratos Wistar , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos
14.
Adv Pharm Bull ; 5(1): 89-96, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25789224

RESUMO

PURPOSE: A protective effect for estrogens against cardiovascular problems has long been known. The aim of this study was to investigate the vasorelaxant effect of 17α-Ethynylestradiol (17α-EE) on human saphenous vein. METHODS: The veins were suspended horizontally between two triangular stainless steel hooks for the measurement of isometric tension in individual organ baths containing 10ml Krebs solution, at 37°C and gassed with carbogen under 3gr optimum tension. The effect of different concentrations of 17α-EE (2-40 µM) on vascular tone was investigated in veins precontracted with PGF2α. Relaxation was measured after 40min and expressed as the percent decrease of initial contraction. To determine the involvement of potassium channels, endothelium, nitric oxide synthase, guanylylcyclase and prostaglandins in the vasorelaxant effect of estrogen, the veins were incubated with tetraethyl ammonium, N-nitro-L-arginine methyl ester, methylene blue or indomethacin, respectively for 20min prior to experimentation. Responses to 17α-EE were directly compared to those obtained in the same tissues in the absence of the inhibitors. RESULTS: The mean relaxations induced by 17α-EE with concentrations of 2, 5, 10, 20 and 40µM in tissues precontracted with PGF2α were 19.8 ±5.5%, 26.1±10.8%, 32.2±7.4%, 48.6±10.8%and56±7.6%, respectively. The results of the inhibition of potassium channels, nitric oxide synthase, guanylylcyclase, cyclooxygenase and removing endothelium in relaxation induced by 17α-EE on precontracted veins with PGF2α proved no significant differences. CONCLUSION: This study showed that 17α-EE has significant vasorelaxant effect on human saphenous vein in a concentration-dependent manner. This effect is probably independent of potassium channels, nitric oxide synthase, guanylylcyclase, prostaglandin synthesis and endothelium functions.

15.
Adv Pharm Bull ; 4(3): 249-54, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24754008

RESUMO

PURPOSE: Hepatotoxicity is one of the most important side effects of the statins therapy as lipid-lowering agents. However, the mechanism(s) of hepatotoxicity induced by these drugs is not clearly understood yet, and no hepatoprotective agent has been developed against this complication. METHODS: The protective effect of N-acetylcysteine (NAC) against statins-induced cytotoxicity was evaluated by using freshly isolated rat hepatocytes. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. This technique is based on liver perfusion with collagenase after removal of calcium ion (Ca2+) with a chelator (ethylene glycol tetra acetic acid (EGTA) 0.5 mM). The level of parameters such as cell death, ROS formation, lipid peroxidation, mitochondrial membrane potential (MMP) in the statins-treated hepatocytes were determined. Additionally, the mentioned markers were assessed in the presence of NAC. RESULTS: Incubation of hepatocytes with the statins resulted in cytotoxicity characterized by an elevation in cell death, increasing ROS generation and consequently lipid peroxidation and impairment of mitochondrial function. Administration of NAC caused reduction in amount of ROS formation, lipid peroxidation and finally, cell viability and mitochondrial membrane potential (MMP) were improved. CONCLUSION: This study confirms that oxidative stress and consequently mitochondrial dysfunction is one of the mechanisms underlying the statins-induced liver injury and treating hepatocytes by NAC (200 µM) attenuates this cytotoxicity.

16.
Adv Pharm Bull ; 4(2): 139-45, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24511477

RESUMO

PURPOSE: This study was aimed to design Objective Structured Field Examination (OSFE) and also standardize the course plan of community pharmacy clerkship at Pharmacy Faculty of Tabriz University of Medical Sciences (Iran). METHODS: The study was composed of several stages including; evaluation of the old program, standardization and implementation of the new course plan, design and implementation of OSFE, and finally results evaluation. RESULTS: Lack of a fair final assessment protocol and proper organized educating system in various fields of community pharmacy clerkship skills were assigned as the main weaknesses of the old program. Educational priorities were determined and student's feedback was assessed to design the new curriculum consisting of sessions to fulfill a 60-hour training course. More than 70% of the students were satisfied and successfulness and efficiency of the new clerkship program was significantly greater than the old program (P<0.05). In addition, they believed that OSFE was a suitable testing method. CONCLUSION: The defined course plan was successfully improved different skills of the students and OSFE was concluded as a proper performance based assessment method. This is easily adoptable by pharmacy faculties to improve the educational outcomes of the clerkship course.

17.
Arh Hig Rada Toksikol ; 65(1): 101-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24535294

RESUMO

Statins are potent cholesterol-lowering drugs that can have serious adverse effects on the muscles and liver. The aim of our in vitro study was to establish the protective effect of coenzyme Q10 (CoQ10, in its optimal dose of 200 µmol L⁻¹) against cytotoxicity induced by atorvastatin, simvastatin, and lovastatin in isolated rat hepatocytes by observing parameters such as cell death, reactive oxygen species formation, lipid peroxidation, mitochondrial membrane potential, and cellular reduced and oxidised glutathione content. Our findings have shown that pretreatment with CoQ10 was effective in reducing the toxic effects of statins in rat hepatocytes. This work demonstrates that the addition of CoQ10 to statin treatment regimens may protect hepatocytes (and also other types of cells) from statin-induced injuries and alleviate their side effects.


Assuntos
Anticolesterolemiantes/toxicidade , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Substâncias Protetoras/farmacologia , Ubiquinona/análogos & derivados , Animais , Atorvastatina/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Hepatócitos/patologia , Dose Letal Mediana , Peroxidação de Lipídeos/efeitos dos fármacos , Lovastatina/toxicidade , Masculino , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sinvastatina/toxicidade , Ubiquinona/farmacologia
18.
J Cardiovasc Pharmacol ; 63(2): 113-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24126565

RESUMO

Xanthine oxidase is an important source of reactive oxygen species; so, it may play a role in the pathogenesis of endothelium dysfunction and its consequences. Allopurinol, a purine analog, is a famous xanthine oxidase inhibitor. This study aimed to investigate possible effects of allopurinol on nitroglycerin tolerance, vasoconstriction, and vasorelaxation in rat aortic ring. Using thoracic aortic rings obtained from male Wistar rats, the effect of allopurinol was examined on nitroglycerin-induced tolerance. In addition, changes of vasoconstriction (by using KCl and phenylephrine) and vasorelaxation (by using carbachol, sodium nitroprusside, and nitroglycerin) were also measured and compared between tissues treated with and without allopurinol. All 3 concentrations of allopurinol (50, 100, and 150 µM) significantly acted against the development of nitroglycerin-induced tolerance in comparison with controls. In terms of vasoconstriction and vasorelaxation, the effect of allopurinol was significant only on carbachol-induced (endothelium related) vasorelaxation in a dose-dependent manner. In conclusion, although allopurinol had no significant effect on the contractile response of the aorta, in accord with the previous data, it significantly intensified endothelium-dependent vasodilation. The inhibitory effect of allopurinol against the development of nitrate-induced tolerance may suggest its clinical benefit and is worth to be studied more extensively.


Assuntos
Alopurinol/farmacologia , Aorta Torácica/efeitos dos fármacos , Nitroglicerina/farmacologia , Xantina Oxidase/antagonistas & inibidores , Alopurinol/administração & dosagem , Animais , Aorta Torácica/metabolismo , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Masculino , Nitroglicerina/administração & dosagem , Fenilefrina/farmacologia , Ratos , Ratos Wistar , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologia
19.
J Biochem Mol Toxicol ; 27(6): 287-94, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23761184

RESUMO

Statins are potent drugs, used as lipid-lowering agents in cardiovascular diseases. Hepatotoxicity is one of the serious adverse effects of statins, and the exact mechanism of hepatotoxicity is not yet clear. In this study, the cytotoxic effects of the most commonly used statins, that is, atorvastatin, lovastatin, and simvastatin toward isolated rat hepatocytes, were evaluated. Markers, such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, and the amount of reduced and oxidized glutathione in the statin-treated hepatocytes, were investigated. It was found that the statins caused cytotoxicity toward rat hepatocytes dose dependently. An elevation in ROS formation, accompanied by a significant amount of lipid peroxidation and mitochondrial depolarization, was observed. Cellular glutathione reservoirs were decreased, and a significant amount of oxidized glutathione was formed. This study suggests that the adverse effect of statins toward hepatocytes is mediated through oxidative stress and the hepatocytes mitochondria play an important role in the statin-induced toxicity.


Assuntos
Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Animais , Atorvastatina , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Hepatócitos/patologia , Ácidos Heptanoicos/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Lovastatina/toxicidade , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pirróis/toxicidade , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sinvastatina/toxicidade
20.
Adv Pharm Bull ; 1(1): 10-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-24312751

RESUMO

INTRODUCTION: DHPEE is a newly synthesized compound by merging the key structural elements in an angiotensin receptor blocker (Telmisartan) with key structural elements in 1,4- dihydropyridine calcium channel blocker (Nifedipine). In this study, we examined dual calcium channel blocking and AT1 antagonist activity for DHPEE. METHODS: The functional inhibitory characteristics of DHPEE were studied in vitro in rat thoracic aorta preparations precontracted by phenylephrine (1µM) or KCl (80µM) or Ang II in normal or calcium-free solutions. RESULTS: Concentration-dependent significant relaxation was observed in aortic rings precontracted with phenylephrine, KCl or Ang II. The tension increment produced by increasing external calcium was also reduced by DHPEE. DHPEE caused a marked decrease in the maximal contractile response of the vasoactive agents and shifted their concentration-response curves to the right. CONCLUSION: DHPEE possesses dual characteristics and cause vasorelaxation by blocking the L-type calcium channels and blocking Ang II receptors (AT1) in rat aortic smooth muscle.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...