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1.
Mol Cell Biochem ; 460(1-2): 151-164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31280436

RESUMO

Diallyl trisulfide (DATS) is distinguished as the most potent polysulfide isolated from garlic. The aim of our study was to investigate effects of oral administration of DATS on healthy and diabetic rats, with special attention on heart function. Rats were randomly divided into four groups: CTRL (healthy rats), DATS (healthy rats treated with DATS), DM (diabetic rats), DM + DATS (diabetic rats treated with DATS). DATS (40 mg/kg of body weight) was administered every other day for 3 weeks, at the end of which rats underwent echocardiography, glycemic measurement and redox status assessment. Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion, after which heart tissue was counterstain with hematoxylin and eosin and cardiac Troponin T staining (cTnT), while expression of Bax, B cell lymphoma 2 (Bcl-2), caspase-3, caspase-9 and superoxide dismutase-2 were examined in the left ventricle. DATS treatment significantly reduced blood glucose levels of diabetic rats, and improved cardiac function recovery, diminished oxidation status, attenuated cardiac remodeling and inhibited myocardial apoptosis in healthy and diabetic rats. DATS treatment causes promising cardioprotective effects on ex vivo-induced ischemia/reperfusion (I/R) injury in diabetic and healthy rat heart probably mediated by inhibited myocardial apoptosis. Moreover, appropriate DATS consumption may provide potential co-therapy or prevention of hyperglycemia and various cardiac complications in rats with DM.


Assuntos
Compostos Alílicos/uso terapêutico , Cardiotônicos/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Sulfetos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Masculino , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia
2.
Gen Physiol Biophys ; 37(5): 515-525, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30307402

RESUMO

The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands - ethylenediamine; 1,2-diaminocyclohexane; 2,2':6',2''-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.


Assuntos
Cisplatino/análogos & derivados , Cisplatino/efeitos adversos , Circulação Coronária/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiologia , Perfusão , Animais , Relação Dose-Resposta a Droga , Hemodinâmica/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
3.
Mol Cell Biochem ; 439(1-2): 19-33, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28766171

RESUMO

Drug-induced oxidative stress can occur in numerous tissues and organ systems (liver, kidney, ear, nervous system, and cardiovascular system). Cancer therapy with cisplatin is associated with side effects to which oxidative stress may contribute. We have compared the influences of cisplatin (reference compound) and its' analogues (dichloro(1,2-diaminocyclohexane)platinum(II) and chloro(2,2':6',2″-terpyridine)platinum(II)) in a model of isolated rat heart using the Langendorff technique. The production of oxidative stress biomarkers, antioxidant enzymes, myocardial damage, and expression of Bax, OH-1, and SODs were studied. Cisplatin and the analogues were perfused at concentration of 10-6 and 10-5 M during 30 min. The results of this study showed that examined platinum complexes had different ability to induce oxidative stress of isolated perfused rat heart. Varying the carrier ligands, such as 1,2-diaminocyclohexane and 2,2':6',2″-terpyridine, related to amino ligands (cisplatin) directly influenced the strength to induce production of oxidative stress biomarkers. Introducing 2,2':6',2″-terpyridine ligands provoked the smallest changes in antioxidant enzymes activity, lipid peroxidation, and expression of heme oxygenase-1, that undoubtedly indicated that this complex had the lowest impact on redox status in heart tissue. These findings may be useful in synthesis of novel platinum analogues with lower potential for oxidative stress induction. However, the fact that platinum complexes could induce toxic effects in the heart by other mechanisms should be taken into the consideration.


Assuntos
Cisplatino/farmacologia , Mitocôndrias Cardíacas/metabolismo , Proteínas Musculares/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Masculino , Mitocôndrias Cardíacas/patologia , Miocárdio/patologia , Perfusão , Ratos , Ratos Wistar
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