Cardiac Troponin-I (cTnI) a Biomarker of Cardiac Injuries Induced by Doxorubicin Alone and in Combination with Ciprofloxacin, Following Acute and Chronic Dose Protocol in Sprague Dawley Rats

Shahzadi, Andleeb; Sonmez, Ikbal; Allahverdi, Oruc; Önal, Burak; Kandaz, Cemre; Özyazgan, Sibel; Akkan, Ahmet Gökhan; Yazıcı, Zeliha

doi:10.3923/ijp.2014.258.266

Cited by 8 publications

(8 citation statements)

References 34 publications

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“…[68] Previously, it has been shown that levels of cTnI are likely to be used for monitoring the extent of DOX-induced cardiac damage in rats. [69][70][71][72] In addition to the above-mentioned marker enzymes, DIC in the present study was evidenced by a significant increase in plasma level of cTnI in DOX-administered mice compared to controls. The cardioprotective effect of TRE was further confirmed by a significant reduction of cTnI level, where treatment with TRE alone or in combination with DOX restored the levels of cTnI towards normal.…”

Section: Discussionsupporting

confidence: 53%

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Abu-Khudir

Ibrahim

Shams

et al. 2021

J Biochem & Molecular Tox

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Clinically, the use of doxorubicin (DOX) is limited due to DOX-induced cardiotoxicity (DIC). The current study aimed to evaluate the cardioprotective effect of trehalose (TRE) against DIC in a female Swiss albino mouse model. Mice were divided into five experimental groups: Gp. I: saline control group (200 μl/mouse saline three times per week for 3 weeks day after day), Gp. II: DOX-treated group (2 mg/kg body weight three times per week for 3 weeks day after day), Gp. III: TRE group (200 μg/mouse three times per week for 3 weeks day after day), Gp. IV: DOX + TRE cotreatment group (animals were coadministered with DOX and TRE as in Gp. II and III, respectively), and Gp. V: DOX + TRE posttreatment group (animals were treated with DOX as in Gp. II followed by treatment with TRE as in Gp. III). DOX-treated mice showed significant elevation in cardiac injury biomarkers (lactate dehydrogenase, creatine kinase isoenzyme-MB, and cardiac troponin I), cardiac oxidative stress (OS) markers (malondialdehyde and myeloperoxidase), and cardiac levels of autophagyrelated protein 5. Moreover, DOX significantly reduced the levels of total antioxidant capacity and activities of catalase and glutathione S-transferase.In contrast, TRE treatment of DOX-administered mice significantly improved almost all of the above-mentioned assessed parameters. Furthermore, histopathological changes of cardiac tissues observed in mice treated with TRE in combination with DOX were significantly improved as compared to DOXtreated animals. Taken together, the present study provides evidence that TRE has cardioprotective effects against DIC, which is likely mediated via suppression of OS and autophagy.

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Section: Discussionsupporting

confidence: 53%

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Abu-Khudir

Ibrahim

Shams

et al. 2021

J Biochem & Molecular Tox

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“…In preclinical and clinical phase studies, troponins (cTnT and cTnI) have been used as highly sensitive plasma biomarkers for detecting DOX-induced cardiac damage (Herman et al 1998, 1999; Lipshultz et al 2012; O’Brien 2006; O’Brien et al 2006; Shahzadi et al 2014). However, troponins and many other cardiac biomarkers show increased plasma levels only after heart tissue damage and also have a limited half-life (Tonomura et al 2009; Walker 2006).…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs as early toxicity signatures of doxorubicin in human-induced pluripotent stem cell-derived cardiomyocytes

et al. 2016

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An in depth investigation at the genomic level is needed to identify early human-relevant cardiotoxicity biomarkers that are induced by drugs and environmental toxicants. The main objective of this study was to investigate the role of microRNAs (miRNAs) as cardiotoxicity biomarkers using human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) that were exposed to doxorubicin (DOX) as a “gold standard” cardiotoxicant. hiPSC-CMs were exposed to 156 nM DOX for 2 days or for 6 days of repeated exposure, followed by drug washout and incubation in drug-free culture medium up to day 14 after the onset of exposure. The induced miRNAs were profiled using miRNA microarrays, and the analysis of the data was performed using the miRWalk 2.0 and DAVID bioinformatics tools. DOX induced early deregulation of 14 miRNAs (10 up-regulated and 4 down-regulated) and persistent up-regulation of 5 miRNAs during drug washout. Computational miRNA gene target predictions suggested that several DOX-responsive miRNAs might regulate the mRNA expression of genes involved in cardiac contractile function. The hiPSC-CMs exposed to DOX in a range from 39 to 156 nM did not show a significant release of the cytotoxicity marker lactate dehydrogenase (LDH) compared to controls. Quantitative real-time PCR analyses confirmed the early deregulation of miR-187-3p, miR-182-5p, miR-486-3p, miR-486-5p, miR-34a-3p, miR-4423-3p, miR-34c-3p, miR-34c-5p and miR-1303, and also the prolonged up-regulation of miR-182-5p, miR-4423-3p and miR-34c-5p. Thus, we identified and validated miRNAs showing differential DOX-responsive expression before the occurrence of cytotoxicity markers such as LDH, and these miRNAs also demonstrated the significant involvement in heart failure in patients and animal models. These results suggest that the DOX-induced deregulated miRNAs in human CMs may be used as early sensitive cardiotoxicity biomarkers for screening potential drugs and environmental cardiotoxicants with a similar mechanism of action.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1668-0) contains supplementary material, which is available to authorized users.

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“…The probable cause of the increase of cTnI level is damage to myocardium 39 . A dosedependent increase in cardiac lesions was previously reported when Fischer rats were treated with 1-2 mg/kg of doxorubicin for up to 10-14 weeks 40, and Wister-Kyoto rats were treated with a cumulative dose of 12 mg/kg of doxorubicin 41 . Previous studies also reported that myocardial injury increased with increase in dose, as observed in Sprague Dawley rats treated with 10, 13.5 and 18 mg/kg of doxorubicin 40 and similar results were observed in the present study.…”

Section: Table 1: Effect Of Different Doses Of Doxorubicin On Serum Cmentioning

confidence: 58%

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2019

IJPSR

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Although doxorubicin is used widely in animal models to induce cardiotoxicity, serial dose-dependent cardiac effects have not been investigated in experimental animal models to date. Therefore, the objective of this study was to find out the dose-dependent changes of doxorubicin-induced acute cardiotoxicity, both biochemically and histopathologically in Wistar rats. Wistar rats were divided into nine groups. Group 1: normal control; Groups 2-9: eight doses of doxorubicin (13, 14, 15, 16, 17, 18, 19 & 20 mg/kg, intraperitoneal injection, after 16 h fast). Animals were sacrificed on the 4 th day, and blood was collected for the estimation of cardiac troponin I (cTnI), aspartate aminotransferase (AST) and superoxide dismutase (SOD) activities and heart tissues were collected for histopathological assessment. Mean cTnI concentrations of

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Cardiac Troponin-I (cTnI) a Biomarker of Cardiac Injuries Induced by Doxorubicin Alone and in Combination with Ciprofloxacin, Following Acute and Chronic Dose Protocol in Sprague Dawley Rats

Cited by 8 publications

References 34 publications

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy

MicroRNAs as early toxicity signatures of doxorubicin in human-induced pluripotent stem cell-derived cardiomyocytes

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