Induction of Antioxidants by Adriamycin in Mouse Heart

Yin, Xianhua; Wu, Huiyun; Chen, Yan; Kang, Y. James

doi:10.1016/s0006-2952(98)00099-9

Cited by 81 publications

(49 citation statements)

References 39 publications

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“…13,14,27,28) Under normal condition, pathophysiological stimuli that increase oxidative stress can up-regulate certain protective molecules such as heme oxygenase (HO)-1, a cytoprotective heme-degrading enzyme, and antioxidants including SOD, catalase and metallothionein in the heart. 40) It was found that HO-1 expression was increased in the mouse hearts subjected to I/R, but I/R-induced up-regulation of HO-1 expression in non-diabetic mice was absent in diabetic hearts. 13) Therefore, the absent expression of HO-1 made the heart more susceptible to I/R-induced damage and diabetes worsened these injuries.…”

Section: Discussionmentioning

confidence: 98%

Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats

Xiao

Lin

et al. 2010

Biological & Pharmaceutical Bulletin

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Diabetes impairs the expression and function of endogenous growth factors, leading to increased cardiovascular events in diabetic patients. Supplementation of fibroblast growth factors (FGFs) protected the heart from ischemia/reperfusion (I/R)-induced injury in animal models. However, it has not yet been tested in diabetic heart. The present study was thus to clarify whether basic fibroblast growth factor (bFGF) could protect the heart from I/R-induced damage under diabetic conditions using a rat model. Male Sprague Dawley rats were used to induce diabetes by intraperitoneal injection of streptozotocin. Eight weeks later, I/R injury was generated in diabetic rats and age-matched non-diabetic rats. All I/R rats were administrated bFGF or saline through intramyocardial injection. Seven days after I/R, cardiac infarction, structural changes, cell death and blood vessel density, serum malondialdehyde (MDA) and cardiac enzyme lactate dehydrogenase (LDH) were examined. We found that I/R induced significant increases in the cardiac infarction, blood MDA contents and LDH activities, and the expression of caspase-3. Treatment of I/R rats with bFGF simultaneously with reperfusion significantly attenuated I/Rinduced pathological changes, along with a significant increase in the cardiac blood vessel density in both diabetic and non-diabetic rates. The protective effects of bFGF on I/R-induced cardiac injury in diabetic group are less than those in non-diabetic group. The results indicated that bFGF provide a protection of the heart against I/R-induced oxidative damage, cell death and infarction under diabetic conditions.

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Section: Discussionmentioning

confidence: 98%

Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats

Xiao

Lin

et al. 2010

Biological & Pharmaceutical Bulletin

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“…5,6 Similar findings have also been reported in rabbits treated with 13.5 mg/kg of adriamycin in 3 weeks. 3 Because a single injection of adriamycin (15 mg/kg) did not have any influence on the activity of GSHPx, 21 it is likely that repeated administration of adriamycin over time is necessary to bring about a decrease in this activity. Furthermore, our data suggest that this decrease in the enzyme activity may be caused by the parallel decrease in the enzyme protein shown by the Western blots in the present study.…”

Section: And Singal Antioxidant Enzymes In Heart Failure 2107mentioning

confidence: 99%

Adriamycin-Induced Early Changes in Myocardial Antioxidant Enzymes and Their Modulation by Probucol

2000

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Background-The clinical usefulness of adriamycin is restricted by the development of congestive heart failure. It has been suggested that probucol, a strong antioxidant, completely prevents adriamycin-induced cardiomyopathy without interfering with its antitumor properties. The present study investigated the effects of adriamycin and probucol on myocardial antioxidant enzyme activities and immunoreactive protein levels in rats. Methods and Results-Activities and protein levels of glutathione peroxidase (GSHPx) were significantly decreased from 2 to 24 hours, and those of manganese superoxide dismutase were decreased at 1 and 2 hours after adriamycin treatment. These changes were prevented by probucol. Catalase activity was increased from 2 to 24 hours after adriamycin treatment, but its protein levels were not significantly changed. Copper zinc superoxide dismutase activity and protein level were not changed at any time. Myocardial lipid peroxidation was found to be significantly higher at all time points, and this change was also prevented by probucol. Treatment with probucol alone increased GSHPx activity at 2 weeks, and in these hearts, lipid peroxidation was lower than the control value. Within 24 hours, there was no mortality in any of the groups. Conclusions-It is suggested that an early and persistent decrease in GSHPx activity and protein may play an important role in the pathogenesis of adriamycin-induced cardiomyopathy, worsening heart failure and mortality. (Circulation.

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“…By day 4, the translational machinery may be sufficiently damaged to incompletely process the transcripts and indeed, lack of translation in the face of increased transcription has been shown (20). At low doses that cumulatively produce the cardiomyopathy, however, it is not until after 8 weeks of dosing that apoptosis is initiated through a Fas-mediated pathway (22).…”

Section: Discussionmentioning

confidence: 99%

Correlation of Simultaneous Differential Gene Expression in the Blood and Heart with Known Mechanisms of Adriamycin-Induced Cardiomyopathy in the Rat

Brown¹,

Benavides²,

Giridhar³

et al. 2002

Toxicologic Pathology

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As the genomes of mammalian species become sequenced and gene functions are ascribed, the use of differential gene expression (DGE) to evaluate organ function will become common in the experimental evaluation of new drug therapies. The ability to translate this technology into useful information for human exposures depends on tissue sampling that is impractical or generally not possible in man. The possibility that the DGE of nucleated cells, reticulocytes, or platelets in blood may present the necessary link with target organ toxicity provides an opportunity to correlate preclinical with clinical outcomes. Adriamycin is highly effective alone and more frequently in combination with other chemotherapeutic agents in the treatment of a variety of susceptible malignancies. Adriamycin-induced cardiomyopathy was examined as an endpoint to measure the utility of DGE on whole blood as a predictor of cardiac toxicity. Statistically significant gene changes were observed between relevant blood and cardiac gene profiles that corroborated the accepted mechanisms of toxicity (oxidative stress, effects on carnitine transport, DNA intercalation). There were, however, clear indications that other target organs (bone marrow and intestinal tract) were affected. The divergent expression of some genes between the blood and the heart on day 7 may also indicate the timing and mechanism of development of the cardiomyopathy and confirm current therapeutic approaches for its prevention. The data demonstrate that whole blood gene expression particularly in relation to oxidative stress, in conjunction with standard hematology and clinical chemistry, may be useful in monitoring and predicting cardiac damage secondary to adriamycin administration.Appendices A & B, referenced in this paper, are not printed in this issue of Toxicologic Pathology. They are available as downloadable text files at http://taylorandfrancis.metapress.com/openurl.asp?genre = journal&issn = 0192-6233. To access them, click on the issue link for 30(4), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org.

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Induction of Antioxidants by Adriamycin in Mouse Heart

Cited by 81 publications

References 39 publications

Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats

Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats

Adriamycin-Induced Early Changes in Myocardial Antioxidant Enzymes and Their Modulation by Probucol

Correlation of Simultaneous Differential Gene Expression in the Blood and Heart with Known Mechanisms of Adriamycin-Induced Cardiomyopathy in the Rat

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