RESUMO
Recent findings implied the significance of reactive oxygen species (ROS) as a part of tyrosine kinase inhibitors (TKIs) pharmacological activity. Evidences also suggested that toxic effects of TKIs were related to ROS production. The results regarding benefits of vitamin E usage alongside with prescribed TKIs therapy are ambiguous. We aimed to examine oxidative stress and antioxidative defense in human serum treated with four different TKIs and their possible interactions with hydrosoluble vitamin E analog (Trolox). An in-vitro experiment with serum pool as a substitute model was performed. Different parameters of oxidative stress and antioxidative defense were measured in serum pool with and without addition of TKIs (axitinib, crizotinib, nilotinib, and imatinib), before and after addition of Trolox. Z score statistic was used for calculation of Prooxidative and Antioxidative scores. The highest oxidative potential was recorded for samples incubated with imatinib and nilotinib, while the lowest damaging scores were observed for crizotinib and axitinib (nilotinib vs. imatinib, P < 0.05; axitinib vs. imatinib, P < 0.01; crizotinib vs. imatinib, P < 0.001). The best capability for antioxidative protection was seen in samples with nilotinib, then with imatinib, while the lowest level was obtained in samples with crizotinib and axitinib (imatinib and axitinib vs. nilotinib, P < 0.05 for both; crizotinib vs. nilotinib, P < 0.01; axitinib vs. imatinib, P < 0.05, crizotinib vs. imatinib, P < 0.01). Our results demonstrated the opposite effects of Trolox in combination with imatinib and nilotinib. Usage of antioxidant in combination with TKIs should be carefully evaluated in each specific case.
Assuntos
Estresse Oxidativo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Soro/efeitos dos fármacos , Soro/metabolismo , Antioxidantes/farmacologia , Cromanos/farmacologia , Humanos , Oxirredução/efeitos dos fármacos , Inibidores de Proteínas Quinases/sangue , Espécies Reativas de Oxigênio/sangueRESUMO
Understanding the cellular stress response in honey bees will significantly contribute to their conservation. The aim of this study was to analyze the response of the antioxidative enzymes superoxide dismutase and catalase in honey bees related to the presence of toxic metals in different habitats. Three locations were selected: (i) Tunovo on the mountain Golija, as control area, without industry and large human impact, (ii) Belgrade as urban area, and (iii) Zajaca, as mining and industrial zone. Our results showed that the concentrations of lead (Pb) in whole body of bees vary according to habitat, but there was very significant increase of Pb in bees from investigated industrial area. Bees from urban and industrial area had increased expression of both Sod1 and Cat genes, suggesting adaptation to increased oxidative stress. However, in spite increased gene expression, the enzyme activity of catalase was lower in bees from industrial area suggesting inhibitory effect of Pb on catalase.
Assuntos
Abelhas/enzimologia , Catalase/análise , Exposição Ambiental/efeitos adversos , Superóxido Dismutase/análise , Animais , Abelhas/genética , Cidades , Feminino , Perfilação da Expressão Gênica , Indústrias , Chumbo/análise , Estresse Oxidativo , Sérvia , Zinco/análiseRESUMO
The present study is designed to investigate whether magnesium (Mg) supplementation may prevent Cd-induced alterations in zinc (Zn), copper (Cu), and magnesium (Mg) status in rabbits. For this purpose, the concentrations of Zn, Cu, and Mg were estimated in blood, urine, and organs (brain, heart, lungs, liver, kidney, spleen, pancreas, skeletal muscle, and bone) of rabbits given Cd (10 mg/kg b.w.) and rabbits cotreated with Mg (40 mg/kg b.w.) orally, as aqueous solutions of Cd chloride and Mg acetate every day for 4 weeks. Samples were mineralized with conc. HNO3 and HClO4 (4:1) and metals concentrations were determined by atomic absorption spectrophotometry (AAS). Magnesium supplementation succeeded to overcome Cd-induced disbalance of investigated bioelements. Beneficial effects of Mg were observed on Zn levels in blood and urine, on Cu levels in urine, and on Mg levels in blood. Magnesium pretreatment also managed to counteract or reduce all Cd-induced changes in levels of Cu and Mg in organs, while it did not exert this effect on Zn levels. These findings suggest that enhanced dietary Mg intake during Cd exposure can have at least partly beneficial effect on Cd-induced alterations in homeostasis of zinc, copper, and magnesium.
Assuntos
Cádmio/toxicidade , Cobre/metabolismo , Suplementos Nutricionais , Magnésio/administração & dosagem , Magnésio/sangue , Distribuição Tecidual/efeitos dos fármacos , Zinco/metabolismo , Administração Oral , Animais , Taxa de Depuração Metabólica/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Coelhos , Resultado do TratamentoRESUMO
Honeybee colony losses have been a focus of research in the last years, due to the importance of managed honeybee colonies for economy and ecology. Different unfavorable conditions from the outside environment have a strong impact on the hive health. The majority of losses occur mainly during winter and the exact reason is not completely understood. Only a small number of studies are dealing with content of bioelements, their function and influence on honeybee physiology. The aim of the present study was to determine seasonal and spatial variations in content of bioelements and non-essential elements, in hemolymph and whole body of honeybees originating from three regions with different degrees of urbanization and industrialization. Concentrations of 16 elements were compared: macroelements (Ca, K, Mg, Na), microelements (Cu, Fe, Mn, Zn) and non-essential elements (Al, Ba, Cd, Co, Cr, Ni, Pb, Sr) in samples collected from 3 different environments: Golija (rural region), Belgrade (urban region) and Zajaca (industrial region). Content of bioelements and non-essential elements in honeybees was under noticeable influence of the surrounding environment, season and degree of honeybee activity. Hemolymph was proven to be helpful in differentiating air pollution from other sources of honeybee exposure. The results of our study demonstrated that bees can be successfully used as biomonitors since we have observed statistically significant differences among observed locations, but unless compared locations are exposed to excessively different pollution pressures, it is essential that all bees should be collected at the same season.
Assuntos
Abelhas/metabolismo , Monitoramento Ambiental/métodos , Poluição Ambiental/análise , Hemolinfa , Metais , Animais , Hemolinfa/química , Desenvolvimento Industrial , Metais/análise , Estações do Ano , Sérvia , UrbanizaçãoRESUMO
Lead manifests toxic effects in almost all organs and tissues, especially in: the nervous system, hematopoietic system, kidney and liver. This metal has a special affinity for deposition in hard tissue, i.e., bones and teeth. It is generally believed that the main mechanism of its toxicity relies on its interaction with bioelements, especially with Ca and Mg. This article analyses the influence of Pb poisoning on Ca and Mg content in hard tissues, (mandible, femur, teeth and skull) of female and young rats. Experiments were carried out on 60 female rats, AO breed, and on 80 of their young rats (offspring). Female rats were divided into three groups: the first one was a control group, the second one received 100 mg/kg Pb2+ kg b.wt. per day in drinking water, the third one received 30 mg/kg Pb(2+) kg b.wt. per day in drinking water. Young rats (offspring) were divided into the same respective three groups. Lead, calcium and magnesium content in hard tissues (mandible, femur, teeth-incisors and skull) was determined by flame atomic absorption spectrophotometry in mineralized samples. There was a statistically significant Pb deposition in all analyzed female and young rat hard tissues. Ca and Mg contents were significantly reduced in all female and young rat hard tissues. These results show that Pb poisoning causes a significant reduction in Ca and Mg content in animal hard tissues, which is probably the consequence of competitive antagonism between Pb and Ca and Mg.
Assuntos
Cálcio/metabolismo , Intoxicação por Chumbo/metabolismo , Chumbo/toxicidade , Magnésio/metabolismo , Animais , Cálcio/sangue , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Intoxicação por Chumbo/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Magnésio/sangue , Mandíbula/efeitos dos fármacos , Mandíbula/metabolismo , Ratos , Crânio/efeitos dos fármacos , Crânio/metabolismo , Dente/efeitos dos fármacos , Dente/metabolismoRESUMO
Biocompatibility of dental materials (DM) can be evaluated by gingival crevicular fluid (GCF) oxidative stress (OS) status. The goal of the study was to ascertain influence of dental caries degree, teeth position, and type and amount of applied DM on GCF OS profile. For this purpose, we tested six DMs that were sealed in one session: amalgam (Amg), composites: Tetric EvoCeram and Beautifil (BF), phosphate cement-zinc phosphate and polycarboxylate cements-zinc polycarboxylate cements, and glass ionomer cement (GIC). The study included 88 dental outpatients. Follow-up was scheduled at 7th and 30th day. Oxidative stress parameters (malondialdehyde (MDA) and glutathione (GSH) levels and total superoxide dismutase (tSOD) activity) were measured before (0th day) and after the treatment (7th and 30th day) in GCF. Control teeth were mirror-positioned healthy teeth. The DM accomplished the following effects (listed in descending order): increase of GSH in GCF was realized by ZPoC > BF > GIC > Amg; tSOD activity increase by ZPoC > BF > Amg; and MDA decrease by ZPoC > ZPhC > Amg > TEC. Dental caries provokes insignificant rise of OS in GCF. ZPoC and ZPhC showed the highest antioxidant effect, contrary to GIC. Restorations with antioxidant properties may reduce gum diseases initiated by caries lesion, what is of great clinical relevance in dentistry.
Assuntos
Cárie Dentária/patologia , Líquido do Sulco Gengival/metabolismo , Adolescente , Adulto , Idoso , Líquido do Sulco Gengival/citologia , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Adulto JovemRESUMO
The objective of our study was to examine testicular toxicity of cadmium (Cd), focusing on oxidative stress (OS), essential metals and androgenic status and morphological changes. Male Wistar rats [controls and four Cd-subgroups (n = 6) organized according to the exposure (1, 3, 10 and 21 days)] were intraperitoneally (i.p.) treated with 1 mg CdCl2/kg/day. Testicular Cd deposition was noticed from the 1st day. After 10 and 21 days, copper (Cu) and iron (Fe) increased by 60-109% and 43-67%, respectively, while zinc (Zn) decreased by 24-33%. During 1-21 days of the exposure, decrease in testicular total superoxide dismutase (SOD) and total glutathione-s-transferase (GST) activities occurred gradually by 30-78% and 15-84%, respectively, while superoxide anion radical (O2(-)) increased gradually by 114-271%. After 10-21 days, decrease in testicular catalase (CAT) activity appeared by 13-31%. After 21 days, malondialdehyde (MDA) decreased by 44% and the ratio of oxidized glutathione/reduced glutathione (GSSG/GSH) increased by 130% in testes of the rats exposed to Cd. Additionally, decreased testicular testosterone level and the relative testes mass, along with induced microscopic and macroscopic changes were occured, what can be explained as the consequence of instantly developed OS, impaired essential metals status and Cd testicular deposition.
Assuntos
Cádmio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Catalase , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Testículo/metabolismoRESUMO
Many authors in different studies have reported the antagonism between Mg and Pb. Our previous results suggested that oral Mg treatment have better effect on investigation biochemical parameters (protoporphyrins, aminolevulinic acid--ALA and d-aminolevulinic dehydratase ALA-D) used in evaluating Pb intoxication, then CaNa2EDTA, chelation agents, currently used in therapy of Pb intoxication. The toxic effect of Pb induced considerably modifies the activity of many other enzymes. In this work we have examined the influence of Mg (as alternative therapy of Pb poisoning) on enzymes activity--biochemical markers for general health conditions--aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in condition of lead intoxication. Many studies showed disturbances of activity ALT, AST and ALP. The aim of this study was to confirm positive effects of Mg intake in condition of such intoxication at the level on activity of investigated enzymes. The experiment was performed on 45 male Wister rats, divided in three groups. I--control group; II--group treated daily for 30 days with 100 mg Pb, per kg body weight and next 60 without Pb treatment (spontaneous detoxication); III group--the same treatment as II group for the first 30 days, but next 60 days rats were treated orally with 40 mg Mg/kg body weight. Activity of AST and ALT was significant increased in condition of Pb poisoning, but ALP activity was significant reduced. Influence of excessive oral Mg treatment was positive: decrease of AST activity and ALT activity, which was probably in correlation with significant elimination of Pb from liver and increase of ALT enzyme activity at the normal level.
Assuntos
Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Aspartato Aminotransferases/metabolismo , Chumbo/farmacocinética , Magnésio/farmacologia , Animais , Intoxicação por Chumbo/enzimologia , Intoxicação por Chumbo/metabolismo , Magnésio/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
Protection from heavy metals is a problem that has not been solved in a satisfactory manner so far. Usage of complexing agents in therapy of exposed workers results in both favorable outcome and recognized adverse effects. In the field of environmental protection, they cannot be used in practice, meaning that the risk of escape of metal pollutant from factory premises and their attack on the environnement remains present. The age of chemistry ('Chemistry, key to better living') has led to potent development of industry producing, at the same time, major problems induced by diffusion of metal pollutants, the nightmare of our times, like Camus' 'Plague'. According to the available results, it remains to be answered whether magnesium may influence this important problem, i.e. is this approaches the issue justifiable?
Assuntos
Poluentes Ambientais/toxicidade , Magnésio/toxicidade , Metais/toxicidade , Animais , Cádmio/toxicidade , Cromo/toxicidade , Poluição Ambiental , Humanos , Manganês/química , Níquel/toxicidade , CoelhosRESUMO
INTRODUCTION: Contact herbicide diquat (DQ), redox cycling compound, mediates its systemic toxicity throughout the enlarged production of free radicals. Target organs are liver and kidney in humans. To-date, the mechanism of DQ-induced neurotoxicity has not been rationalized. OBJECTIVE: The objectives of the study were to examine the ability of DQ to induce oxidative stress (OS) and/or nitrosative stress (NS) upon intrastriatal (i.s.) administration and to investigate the role of nitric oxide (NO(x)) using NG-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric oxide synthase (NOS) in the pretreatment of DQ i.s. administration. MATERIAL AND METHODS: The experiment was conducted on Wistar rats, randomly divided in experimental groups, receiving different treatments i.s. applied. Parameters of OS/NS such as: superoxide anion radical (O(2)(â¢-)), superoxide dismutase (SOD), malondialdehyde (MDA) and nitrates (NO(3)(-)) were measured in the cortex (bilaterally), at 30(th) min, 24 hours and 7 days after the treatments. RESULTS: Lethargy and high mortality rate were observed only in the DQ group (within 24 hours and 2-3 hours, respectively) after awakening from anesthesia. Markedly increased production of NO(x) and O(2)(â¢-) along with elevated lipid peroxidation altogether contributed to DQ neurotoxicity. The most importantly, the L-NAME i.s. pretreatment protected treated animals from dying and diminished OS/NS response against DQ-induced neurotoxicity. CONCLUSION: The i.s. pretreatment with L-NAME resulted in neuroprotection against DQ neurotoxity, based on animal survival and reduced LPO in the cortex.