Plasma nitric oxide levels used as an indicator of doxorubicin-induced cardiotoxicity in rats

Guerra, Jhon; Jesús, Ana de; Santiago-Borrero, Pedro J.; Roman-Franco, Angel; Rodríguez, Edwin; Crespo, Marı́a J.

doi:10.1038/sj.thj.6200573

Cited by 26 publications

(19 citation statements)

References 21 publications

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“…Further, arginine represents a by-product of nitric oxide formation. A previous study showed that nitric oxide levels were decreased in DOX-induced congestive heart failure suggesting the possible role of plasma nitric oxide levels in DOX-induced cardiotoxicity[38, 39]. In the present metabolomics study, we found serum citrulline level was decreased in DZR treatment group and increased in the DOX+ DZR treatment group.…”

Section: Discussionsupporting

confidence: 60%

Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study

Yang

Wan

et al. 2017

PLoS ONE

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Cardioprotection of dexrazoxane (DZR) against doxorubicin (DOX)-induced cardiotoxicity is contentious and the indicator is controversial. A pairwise comparative metabolomics approach was used to delineate the potential metabolic processes in the present study. Ninety-six BALB/c mice were randomly divided into two supergroups: tumor and control groups. Each supergroup was divided into control, DOX, DZR, and DOX plus DZR treatment groups. DOX treatment resulted in a steady increase in 5-hydroxylysine, 2-hydroxybutyrate, 2-oxoglutarate, 3-hydroxybutyrate, and decrease in glucose, glutamate, cysteine, acetone, methionine, asparate, isoleucine, and glycylproline.DZR treatment led to increase in lactate, 3-hydroxybutyrate, glutamate, alanine, and decrease in glucose, trimethylamine N-oxide and carnosine levels. These metabolites represent potential biomarkers for early prediction of cardiotoxicity of DOX and the cardioprotective evaluation of DZR.

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Section: Discussionsupporting

confidence: 60%

Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study

Yang

Wan

et al. 2017

PLoS ONE

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“…While the basal NO production regulates the cardiomyocyte contractility and the blood flow, the excessively produced NO is involved in cardiac pathologies such as dilated cardiomyopathy and congestive cardiac failure [9,17,18,19]. Recent trials reported that NO was involved in the cardiotoxicity of DOX [10,11,13,20,21]. …”

Section: Discussionmentioning

confidence: 99%

“…The literature data included reduced activity, weight loss, and acid formation as the clinical findings for DOX-associated toxicity. Guerra et al reported that those with cardiomyopathy findings among rats that were administered a cumulative DOX dose of 13.5 mg/kg had significantly lower weight gain relative to the control group [11]. In the trial by Hirano et al, the rats receiving intravenous DOX weekly at a dose of 1.25 mg/kg (total dose: 5 mg/kg) and 2.5 mg/kg for 4 weeks (total dose: 10 mg/kg) exhibited reduction in weight in line with the cardiomyopathy findings; this was particularly marked in the group receiving the dose of 2.5 mg/kg/week [22].…”

Section: Discussionmentioning

confidence: 99%

“…The histopathological investigation of the rat hearts revealed findings of cardiac injury, and the plasma NO level was markedly higher compared to the control group. This study detected a positive correlation between the cardiomyopathy score and the NO level [11]. Sayed-Ahmed et al measured the cardiac NO level after administering a single high dose (20 mg/kg) and gradually increasing daily doses of DOX (5-25 mg/kg) in rats.…”

Section: Discussionmentioning

confidence: 99%

“…Recent trials have demonstrated that NO is involved in the cardiotoxicity associated with DOX. It was shown that DOX increased NO synthesis in plasma and cardiac tissue [10,11]. NO increase is believed to be mediated by inducible NO synthase (iNOS) and endothelial NO synthase (eNOS) enzymes [12,13].…”

Section: Introductionmentioning

confidence: 99%

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The Role of Nitric Oxide in Doxorubicin-Induced Cardiotoxicity: Experimental Study

Bahadır¹,

Kurucu²,

Kadıoğlu³

et al. 2014

Tjh

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Objective: We evaluated the myocardial damage in rats treated with doxorubicin (DOX) alone and in combination with nitric oxide synthase (NOS) inhibitors.Materials and Methods: Twenty-four male Sprague Dawley rats (12 weeks old, weighing 262±18 g) were randomly assigned into 4 groups (n=6). Group I was the control group. In Group II, rats were treated with intraperitoneal (ip) injections of 3 mg/kg DOX once a week for 5 weeks. In Group III, rats received weekly ip injections of 30 mg/kg L-NAME (nonspecific NOS inhibitor) 30 min before DOX injections for 5 weeks. In Group IV, rats received weekly ip injections of 3 mg/kg L-NIL (inducible NOS inhibitor) 30 min before DOX injections for 5 weeks. Rats were weighed 2 times a week. At the end of 6 weeks, hearts were excised and then fixed for light and electron microscopy evaluation and tissue lipid peroxidation (malondialdehyde). Blood samples were also obtained for measuring plasma lipid peroxidation. Results: Weight loss was observed in Group II, Group III, and Group IV. Weight loss was statistically significant in the DOX group. Findings of myocardial damage were significantly higher in animals treated with DOX only than in the control group. Histopathological findings of cardiotoxicity in rats treated with DOX in combination with L-NAME and L-NIL were not significantly different compared with the control group. The level of plasma malondialdehyde in the DOX group (9.3±3.4 µmol/L) was higher than those of all other groups. Conclusion: Our results showed that DOX cardiotoxicity was significantly decreased when DOX was given with NO synthase inhibitors.

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In Vivo and In Vitro Studies on the Antioxidant Activity of Aloin Compared to Doxorubicin in Rats

Esmat

Said

Hamdy

et al. 2012

Drug Development Research

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Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IV In the present study, the cardiotoxicity of aloin, a naturally occurring anthraquinone glycoside with antiproliferative activity was compared with doxorubicin, a cardiotoxic anthracyline drug, in rats. The antioxidant and iron‐chelating activities of aloin and doxorubicin in vitro were also evaluated. Rats treated with aloin (50 mg/kg body weight, intramuscular)) twice weekly over 2 weeks showed no signs of cardiotoxicity as assessed by an absence of changes in relative heart weight, serum level of heart function enzymes, and a lack of degeneration in the myocardium of the left ventricle. Acute doxorubicin administration (30 mg/kg body weight, intraperitoneal) to rats produced severe cardiotoxicity as supported by biochemical and histological studies. Aloin did not induce oxidative stress or enhance the endogenous antioxidant defense system in the heart. In vitro antioxidant tests showed that aloin, in contrast to doxorubicin, had substantial antioxidant activity represented by scavenging of 1,1‐diphenyl 2‐picrylhydrazyl and nitric oxide· radicals, inhibition of lipid peroxidation, and ferric‐reducing antioxidant activity in addition to iron chelating potential. Ventricular inducible nitric oxide synthase protein expression was unaffected by either aloin and doxorubicin treatments. In conclusion, repeated aloin treatment, in contrast to that of doxorubicin, failed to produce oxidative stress‐induced cardiotoxicity in the rats.

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Plasma nitric oxide levels used as an indicator of doxorubicin-induced cardiotoxicity in rats

Cited by 26 publications

References 21 publications

Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study

Protective Effects of Dexrazoxane against Doxorubicin-Induced Cardiotoxicity: A Metabolomic Study

The Role of Nitric Oxide in Doxorubicin-Induced Cardiotoxicity: Experimental Study

In Vivo and In Vitro Studies on the Antioxidant Activity of Aloin Compared to Doxorubicin in Rats

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