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1.
Curr Med Chem ; 25(3): 391-403, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-28685675

RESUMO

BACKGROUND: Cisplatin is one the most frequently used chemotherapeutic drugs for several decades. Although its antineoplastic effect has been reported in treatment of numerous malignances, various adverse effects seem to be the crucial limiting factor for its administration. OBJECTIVE: Beside the most commonly described nephro- and hepatotoxicity, cisplatin therapy is also accompanied with gastrointestinal, reproductive, hematological, cardiovascular and neurological side effects. Since it has been reported that cisplatin induce oxidative damage in various tissues, it seems reasonable to investigate an antioxidant supplementation as potential therapeutical approach for attenuation of cisplatin toxicities. METHODS: We performed a structured search of bibliographic databases for research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers (101 in total) was appraised using standard tools. RESULTS: Numerous antioxidants (such as thiol compounds, polyphenols, vitamins, etc.) had been reported for their beneficial effects on cisplatin-induced cardiotoxicity. The effects of various antioxidants, including sulfur-containing amino acids, have also been explored for mitigation of cisplatin neurotoxicity. However, the results for antioxidant supplementation in reduction of cisplatin-induced toxicities are still to be applied in clinical trials. CONCLUSION: Considering the facts that sulfur-containing amino acids: (a) do not interfere with chemotherapeutics antitumor action; (b) do not exhibit any toxic effect (unless applied in dose several times above the recommended); and (c) produce significant protective effects on some cisplatin-induced toxicities connected to augmentation of oxidative damage - it seems that their administration can be harmless and protective supplementation against numerous adverse effects of certain antineoplastic agents.


Assuntos
Aminoácidos/farmacologia , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Cisplatino/efeitos adversos , Síndromes Neurotóxicas/tratamento farmacológico , Enxofre/farmacologia , Aminoácidos/química , Animais , Antioxidantes/química , Cisplatino/uso terapêutico , Ratos , Enxofre/química
2.
J. physiol. biochem ; 73(1): 141-153, feb. 2017. tab, graf
Artigo em Inglês | IBECS | ID: ibc-168401

RESUMO

The role of N-methyl-D-aspartate receptor (NMDA-R) in heart is still unclear. For these ionotropic glutamate receptors is characteristic the necessity of both co-agonists, glutamate and glycine, for their activation, which primarily allows influx of calcium. The aim of the present study was to examine the effects of verapamil, as a calcium channel blocker, alone and its combination with glycine and/or glutamate on cardiac function, coronary flow, and oxidative stress in isolated rat heart or to examine the effects of potential activation of NMDA-R in isolated rat heart. The hearts of male Wistar albino rats were excised and perfused according to Langendorff technique, and cardiodynamic parameters and coronary flow were determined during the administration of verapamil and its combinations with glutamate and/or glycine. The oxidative stress biomarkers, including thiobarbituric acid-reactive substances, nitrites, superoxide anion radical, and hydrogen peroxide, were each determined spectrophotometrically from coronary venous effluent. The greatest decline in parameters of cardiac contractility and systolic pressure was in the group that was treated with verapamil only, while minimal changes were observed in group treated with all three tested substances. Also, the largest changes in coronary flow were in the group treated only with verapamil, and at least in the group that received all three tested substances, as well as the largest increase in oxidative stress parameters. Based on the obtained results, it can be concluded that NMDA-R activation allows sufficient influx of calcium to increase myocardial contractility and systolic pressure, as well as short-term increase of oxidative stress (AU)


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Assuntos
Animais , Masculino , Circulação Coronária , Estresse Oxidativo , Bloqueadores dos Canais de Cálcio/farmacologia , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Verapamil/farmacologia , Receptores de N-Metil-D-Aspartato/agonistas , Sinalização do Cálcio , Contração Miocárdica , Biomarcadores , Técnicas In Vitro , Ratos Wistar , Vasoconstrição , Vasodilatadores/farmacologia
3.
J Physiol Biochem ; 73(1): 141-153, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27812957

RESUMO

The role of N-methyl-D-aspartate receptor (NMDA-R) in heart is still unclear. For these ionotropic glutamate receptors is characteristic the necessity of both co-agonists, glutamate and glycine, for their activation, which primarily allows influx of calcium. The aim of the present study was to examine the effects of verapamil, as a calcium channel blocker, alone and its combination with glycine and/or glutamate on cardiac function, coronary flow, and oxidative stress in isolated rat heart or to examine the effects of potential activation of NMDA-R in isolated rat heart. The hearts of male Wistar albino rats were excised and perfused according to Langendorff technique, and cardiodynamic parameters and coronary flow were determined during the administration of verapamil and its combinations with glutamate and/or glycine. The oxidative stress biomarkers, including thiobarbituric acid-reactive substances, nitrites, superoxide anion radical, and hydrogen peroxide, were each determined spectrophotometrically from coronary venous effluent. The greatest decline in parameters of cardiac contractility and systolic pressure was in the group that was treated with verapamil only, while minimal changes were observed in group treated with all three tested substances. Also, the largest changes in coronary flow were in the group treated only with verapamil, and at least in the group that received all three tested substances, as well as the largest increase in oxidative stress parameters. Based on the obtained results, it can be concluded that NMDA-R activation allows sufficient influx of calcium to increase myocardial contractility and systolic pressure, as well as short-term increase of oxidative stress.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Circulação Coronária/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Glicina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/agonistas , Verapamil/farmacologia , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Bloqueadores dos Canais de Cálcio/química , Sinalização do Cálcio/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/metabolismo , Vasos Coronários/fisiologia , Coração/efeitos dos fármacos , Coração/fisiologia , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/metabolismo , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/farmacologia , Verapamil/antagonistas & inibidores
4.
Mol Cell Biochem ; 411(1-2): 95-105, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26361780

RESUMO

For the past 40 years, anabolic-androgenic steroids have been used by a wide variety of athletes with the hope of improving their training, endurance, and performance. The aim of this study was to examine the chronic effects of nandrolone decanoate (20 mg/kg, s.c, Deca-Durabolin DECA(®)) on oxidative stress biomarkers in the hearts of sedentary and exercised rats. The male Wistar albino rats (n = 180, four groups with three subgroups, 15 per subgroup, age 10 weeks, body mass 200-220 g) were sacrificed, and in the collected samples of blood, the following markers of oxidative stress were measured spectrophotometrically: (1) index of lipid peroxidation (measured as TBARS-thiobarbituric acid reactive substances); (2) nitrites (NO2 (-)); (3) hydrogen peroxide (H2O2); (4) superoxide anion radical (O2 (-)), and superoxide dismutase, catalase, and glutathione reductase. The results clearly show that the impact of ND alone, or in combination with physical training in general, is mildly pro-oxidative. The chronic physical training probably induces the protective antioxidant enzyme system , which may be of clinical interest when faced with overdosage of this drug.


Assuntos
Anabolizantes/administração & dosagem , Nandrolona/análogos & derivados , Condicionamento Físico Animal , Animais , Catalase/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos , Nandrolona/administração & dosagem , Decanoato de Nandrolona , Oxirredução , Ratos , Superóxido Dismutase/metabolismo
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