Dantrolene Attenuates Cardiotoxicity of Doxorubicin Without Reducing its Antitumor Efficacy in a Breast Cancer Model.
Transl Oncol. 2020 Jan 06;13(2):471-480
Authors: Todorova VK, Siegel ER, Kaufmann Y, Kumarapeli A, Owen A, Wei JY, Makhoul I, Klimberg VS
Abstract
Dysregulation of calcium homeostasis is a major mechanism of doxorubicin (DOX)-induced cardiotoxicity. Treatment with DOX causes activation of sarcoplasmic reticulum (SR) ryanodine receptor (RYR) and rapid release of Ca2+ in the cytoplasm resulting in depression of myocardial function. The aim of this study was to examine the effect of dantrolene (DNT) a RYR blocker on both the cardiotoxicity and antitumor activity of DOX in a rat model of breast cancer. Female F344 rats with implanted MAT B III breast cancer cells were randomized to receive intraperitoneal DOX twice per week (12 mg/kg total dose), 5 mg/kg/day oral DNT or a combination of DOX + DNT for 3 weeks. Echocardiography and blood troponin I levels were used to measure myocardial injury. Hearts and tumors were evaluated for histopathological alterations. Blood glutathione was assessed as a measure of oxidative stress. The results showed that DNT improved DOX-induced alterations in the echocardiographic parameters by 50%. Histopathologic analysis of hearts showed reduced DOX induced cardiotoxicity in the group treated with DOX + DNT as shown by reduced interstitial edema, cytoplasmic vacuolization, and myofibrillar disruption, compared with DOX-only-treated hearts. Rats treated with DNT lost less body weight, had higher blood GSH levels and lower troponin I levels than DOX-treated rats. These data indicate that DNT is able to provide protection against DOX cardiotoxicity without reducing its antitumor activity. Further studies are needed to determine the optimal dosing of DNT and DOX in a tumor-bearing host.
PMID: 31918212 [PubMed - as supplied by publisher]
15:34
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
15:34
In reply to this message
pubmed: tutte cardiotoxicity...
Reappraisal of Inflammatory Biomarkers in Heart Failure.
Reappraisal of Inflammatory Biomarkers in Heart Failure.
Curr Heart Fail Rep. 2020 Jan 08;:
Authors: Chaikijurajai T, Tang WHW
Abstract
PURPOSE OF REVIEW: Inflammation has been shown to be an important factor in the development and progression of heart failure (HF), regardless of the etiology. There have been many studies that demonstrated roles of inflammatory biomarkers in diagnosis, prognosis of chronic and acute HF patients, and also markers of cardiotoxicity from chemotherapy. These cytokines are high-sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), soluble growth stimulation expressed gene 2 (sST2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), growth differentiation factor-15 (GDF-15), endothelin-1 (ET-1), and galectin-3. In this review, we discuss the past and present insights of those inflammatory biomarkers in order to gain more understanding in pathogenesis of HF, risk stratification of HF patients, and early detection of cardiotoxicity from cancer therapy.
RECENT FINDINGS: Many inflammatory cytokines have been shown to be associated with mortality of both chronic and acute HF patients, and some of them are able to track treatment responses, especially sST2 and galectin-3, which are the only two inflammatory biomarkers recommended to use in clinical setting by the recent standard HF guidelines, while some studies described ET-1 and MPO as potential predictors of cardiotoxicity from cancer drugs. The prognostic implications of inflammatory biomarkers in HF patients have been demonstrated more consistently in chronic than acute HF, with some suggestions of ET-1 and MPO in patients receiving chemotherapy. However, further studies are necessary for the use of inflammatory biomarkers in routine clinical practice.
PMID: 31916187 [PubMed - as supplied by publisher]
15:34
Photo
Not included, change data exporting settings to download.
256×256, 6.0 KB
15:34
In reply to this message
pubmed: tutte cardiotoxicity...
Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats.
Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats.
Cancer Chemother Pharmacol. 2020 Jan 08;:
Authors: Sheibani M, Nezamoleslami S, Faghir-Ghanesefat H, Emami AH, Dehpour AR
Comments
Post a Comment
اكتب تعليق حول الموضوع