Study of the myocardial antioxidant defence in various species

Takś, I.E.; Matkovics, B.; Varga, Sz.I.; Homolay, P.; Fehér, Gy.; Seres, Tamás

doi:10.1016/1043-6618(92)90348-f

Cited by 18 publications

(12 citation statements)

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“…The heart is particularly vulnerable to damage induced by free radicals because protective enzymes such as superoxide dismutase and catalase are present at a lower level than in other tissues of the body [15,16]. The use of antioxidants to prevent DOX-induced toxicity may be a prudent strategy.…”

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

Ch¹,

Jagetia²,

Lalnuntluangi³

2016

Biochem Mol Biol J

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Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

Ch¹,

Jagetia²,

Lalnuntluangi³

2016

Biochem Mol Biol J

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“…2 ) radicals) (Olson and Mushlin, 1990;Takacs et al, 1992;Goeptar et al, 1994). Reactive oxygen species affect heart tissue specifically because of its relatively low antioxidants content (e.g.…”

mentioning

confidence: 99%

“…Reactive oxygen species affect heart tissue specifically because of its relatively low antioxidants content (e.g. SOD and catalase) and the relative abundance of mitochondria (Takacs et al, 1992).…”

mentioning

confidence: 99%

The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro

et al. 2003

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Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo. It is not known yet whether monoHER can also protect against doxorubicin-induced inflammatory effects. The aim of the present study was (1) to illustrate the inflammatory effects of doxorubicin in vitro and (2) to evaluate a possibly protective effect of monoHER. In order to demonstrate the inflammatory effects of doxorubicin and the possible protection of monoHER, proliferating human umbilical cord vascular endothelial cells (HUVECs) were incubated with different concentrations of doxorubicin ranging from 12.5 to 600 nM with(out) 200 mM monoHER. Resting (confluent) HUVECs were incubated with (0.5 -25 mM) doxorubicin with(out) monoHER (0.2 -1.2 mM) and the viability of endothelial cells and their propensity to adhere to neutrophils were measured 24 h after treatment. The localisation of adhered neutrophils was determined with immunofluorescence microscopy. To further characterise the mechanism of doxorubicin-induced neutrophil adhesion, the expression of the HUVECs surface adhesion molecules was determined after doxorubicin treatment. Doxorubicin decreased the viability and proliferation capacity of HUVECs in a concentration-dependent manner. The proliferating HUVECs were much more sensitive to doxorubicin (IC 50 ¼ 60.0720.8 nM) than resting cells (LC 50 ¼ 4.070.3 mM). Doxorubicin also increased the adhesion of neutrophils reaching a plateau value at a doxorubicin concentration of X0.4mM (P ¼ 0.0113). The induced neutrophil adhesion was accompanied by overexpression of VCAM and E-selectin but not ICAM. Although monoHER did not reverse the effect of doxorubicin on the proliferation of endothelial cells, it significantly protected resting HUVECs against the cytotoxic effect of doxorubicin (p25 mM, Po0.0015). In addition, monoHER completely protected against the stimulatory effect of doxorubicin on neutrophil adhesion, and inhibited the doxorubin-induced expression of VCAM and E-selectin on the surface of treated HUVECs. This study illustrates that monoHER, which protects against doxorubicin's cardiotoxic effect, can also protect against doxorubicin-induced inflammatory effects. These data prompt further investigation about the possible link between doxorubicin-induced inflammatory effects and its cardiotoxicity in vivo.

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“…The cardioprotection of monoHER was attributed to its potent free radical scavenging and metal ion chelating properties 7,8 and thus compensating for the low antioxidants content of the heart tissue. [9][10][11][12] Alternatively, the antioxidant capacity of the heart tissue can be directly enhanced by increasing the level of antioxidant enzymes inherently present in the heart tissue of doxorubicin-treated animals. Among these enzymes comes superoxide dismutase (sod) as an essential player in the detoxification of free radicals.…”

mentioning

confidence: 99%

The protective effect of cardiac gene transfer of CuZn–sod in comparison with the cardioprotector monohydroxyethylrutoside against doxorubicin-induced cardiotoxicity in cultured cells

et al. 2003

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Doxorubicin-induced cardiotoxicity is related to its production of free radicals that specifically affect heart tissue because of its low antioxidant status. Monohydroxyethylrutoside (monoHER), a potent antioxidant flavonoid, is under development as a protector against doxorubicin-induced cardiotoxicity. The overexpression of high levels of superoxide dismutase (sod) protects against free radical damage in transgenic mice. Seeking alternatives besides the few cardioprotectors that are presently under investigation, the aim of the present study was to investigate the protective effect of cardiac gene transfer of CuZn-sod compared with that of the presently most promising cardioprotector monoHER against doxorubicin-induced cardiotoxic effects on neonatal rat cardiac myocytes (NeRCaMs) in vitro. NeRCaMs were infected with different multiplicity of infections (MOIs) of adenovirus encoding CuZn-sod (AdCuZn-sod). A control infection with an adenovirus vector encoding a nonrelated protein was included. The overexpression of CuZn-sod was characterized within 3 days postinfection.For doxorubicin treatment, NeRCaMs were divided into three groups. The first group was infected with AdCuZn-sod before treatment with doxorubicin (0-50 mM). The second and third groups were treated with doxorubicin (0-50 mM) alone and with 1 mM monoHER, respectively. The LDH release and survival of treated cells were measured 24 and 48 hours after doxorubicin treatment. The beating rate was followed during the 3 days after doxorubicin (0-100 mM) treatment.At the third day after infection with an MOI of 25 plaque-forming unit (PFU) of AdCuZn-sod/cell, the activity of CuZn-sod significantly increased (five-fold, P ¼ .029). Higher MOI produced cytopathic effects (CPEs).Doxorubicin alone produced significant concentration-and time-dependent reduction in NeRCaMs beating rate and survival (Po.0005). Doxorubicin (X50 mM)-treated cells ceased to beat after 24 hours. This cytotoxicity was associated with an increase in the LDH release from the treated cells (Po.0005).The five-fold increase in the activity of CuZn-sod did not protect against any of the cytotoxic effects of doxorubicin on NeRCaMs. In contrast, monoHER (1 mM) protected against the lethal effects of doxorubicin on the survival, LDH release and the beating rate of NeRCaMs (Po.004) during 48 hours after doxorubicin treatment. Doxorubicin-treated (r100 mM) cells continued beating for 472 hours in the presence of monoHER.The present study showed the lack of adenoviral CuZn-sod gene-transfer to protect myocardiocytes against doxorubicin-induced toxicity and confirms the efficacy of monoHER cardioprotection. Thus, a gene-therapy strategy involving overexpression of CuZnsod to protect against doxorubicin-induced cardiotoxicity is not feasible with the currently available adenovirus vectors.

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Study of the myocardial antioxidant defence in various species

Cited by 18 publications

References 1 publication

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

The Citrus Flavanone Naringin Enhances Antioxidant Status in the Albino Rat Liver Treated with Doxorubicin

The new cardioprotector Monohydroxyethylrutoside protects against doxorubicin-induced inflammatory effects in vitro

The protective effect of cardiac gene transfer of CuZn–sod in comparison with the cardioprotector monohydroxyethylrutoside against doxorubicin-induced cardiotoxicity in cultured cells

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