Caspase-3 activation and increased procollagen type I in irradiated hearts

Ferreira-Machado, Samara Cristina; Salata, Camila; Rocha, Nazareth N.; Corrêa, Alexandre F.S.; Cortê-Real, Suzana; Peregrino, Antônio Augusto de Freitas; Campos, Vera Maria Araújo de; Andrade, Cherley Borba Vieira de; Bernardo-Filho, Mário; Cabral‐Neto, Januário B.; deAlmeida, C. E.

doi:10.1590/s0001-37652013005000009

Cited by 10 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are in accordance with radiation-induced apoptosis in other organs, showing increased numbers of apoptotic cells from 6 h to several weeks after irradiation (36–38). However, a recent study has demonstrated the presence of cleaved–caspase 3 at 13 months after local heart irradiation in the rat (14). Hence, we cannot exclude that apoptosis may occur again at time points beyond 9 months in our rat model of local heart irradiation.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, mitochondria are sensitive to radiation and become a direct target of radiation damage within hours after exposure (12). Studies have shown that local heart irradiation can cause morphological damage in cardiac mitochondria (13, 14), and nontransient mitochondrial functional alterations including impairment of the respiratory chain and increased protein oxidation (15, 16). Irradiation has also been shown to increase the mitochondrial mass of certain cells in culture (17–19).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Radiation-Induced Alterations in Mitochondria of the Rat Heart

et al. 2014

View full text Add to dashboard Cite

Radiation therapy for the treatment of thoracic cancers may be associated with radiation-induced heart disease (RIHD), especially in long-term cancer survivors. Mechanisms by which radiation causes heart disease are largely unknown. To identify potential long-term contributions of mitochondria in the development of radiation-induced heart disease, we examined the time course of effects of irradiation on cardiac mitochondria. In this study, Sprague-Dawley male rats received image-guided local X irradiation of the heart with a single dose ranging from 3–21 Gy. Two weeks after irradiation, left ventricular mitochondria were isolated to assess the dose-dependency of the mitochondrial permeability transition pore (mPTP) opening in a mitochondrial swelling assay. At time points from 6 h to 9 months after a cardiac dose of 21 Gy, the following analyses were performed: left ventricular Bax and Bcl-2 protein levels; apoptosis; mitochondrial inner membrane potential and mPTP opening; mitochondrial mass and expression of mitophagy mediators Parkin and PTEN induced putative kinase-1 (PINK-1); mitochondrial respiration and protein levels of succinate dehydrogenase A (SDHA); and the 70 kDa subunit of complex II. Local heart irradiation caused a prolonged increase in Bax/Bcl-2 ratio and induced apoptosis between 6 h and 2 weeks. The mitochondrial membrane potential was reduced until 2 weeks, and the calcium-induced mPTP opening was increased from 6 h up to 9 months. An increased mitochondrial mass together with unaltered levels of Parkin suggested that mitophagy did not occur. Lastly, we detected a significant decrease in succinate-driven state 2 respiration in isolated mitochondria from 2 weeks up to 9 months after irradiation, coinciding with reduced mitochondrial levels of succinate dehydrogenase A. Our results suggest that local heart irradiation induces long-term changes in cardiac mitochondrial membrane functions, levels of SDH and state 2 respiration. At any time after exposure to radiation, cardiac mitochondria are more prone to mPTP opening. Future studies will determine whether this makes the heart more susceptible to secondary stressors such as calcium overload or ischemia/reperfusion.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Radiation-Induced Alterations in Mitochondria of the Rat Heart

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Those are characteristcs of healthy cardiac tissue, as shown in the literature by echocardiography, electron microscopy, diffusion tensor (DT) and Magnetic Resonance (MR) images acquired ex vivo [54] [55]. Cardiotoxic agents causes alterations in this pattern, including disorganization of myofibrils and mitochondria, vacuolization of the cytoplasm, and degeneration of crista inside the mitochondria [56] that we could observe on the Figure 2 We can note that previous studies cited in this work did not use any image technique to obtain low-Z elemental and structural information about the health tissue although, it is important to know how some elements are distributed to study any problem on the cardiac tissue.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Low-Z Elements Distribution in Heart Tissue after Treatments to Breast Cancer Using LEXRF Technique

Mantuano¹,

Barroso²,

Nogueira³

et al. 2016

AJAC

Self Cite

View full text Add to dashboard Cite

Data from Global Cancer Statistics show that breast cancer (BC) is the most common type of cancer among women, leading the number of deaths caused by cancer. The developments in diagnosis and treatment techniques for the BC, including chemotherapy and/or radiotherapy, increased the survival rates for this type of cancer. One late complication induced by BC treatment is the cardiotoxicity. This term comprises different cardiotoxic side effects, which include blood pressure alterations, myocardial ischemia, congestive heart failure and other damages. This study aimed to evaluate the cardiac alterations induced by radiotherapy and chemotherapy, simulating a treatment for BC in Wistar rats. It is, therefore, important to understand the mechanisms involved in the cardiotoxicity, in order to prevent women from this late effect, when they undergo BC treatments. The major interests in this work are in Low atomic weight elements as Sodium, because it is strongly related to cardiomyocyte contraction; Magnesium, because it is important in the cardiac metabolism; and Iron, because BC treatment induced cardiotoxicity can be associated to the oxidative stress. Changes that occur in unhealthy tissues in case to cardiovascular damages can be better understood when elemental compounds and structures of healthy tissues are known. Low Energy X-ray Fluorescence (LEXRF) technique was used to obtain elemental maps of low Z-elements providing a semi-quantitative analysis of the tissues evaluated under different conditions. Through the technique LEXRF we obtained elemental and absorption maps. The results showed more damages when associating chemotherapy and radiotherapy in comparison to myocardium healthy. Those images taken together with light microscopy, X-ray absorption and phase How to cite this paper: Mantuano, A., Barroso, R.C., Nogueira, L.P., Colaço, M.V., Mota, C.L., Pickler, A., Braz, D., Salata, C., Ferreira-Machado, S., de Almeida, C.E. and 755contrast images, satisfactorily characterize the cardiac tissue for the first time in the literature, from the structural and morphological points of view. LEXRF was carried out at TwinMic beamline in the ELETTRA Synchrotron Facility, at the beamline TwinMic, in Trieste, Italy.

show abstract

“…Additionally, although a large number of centers still uses 2 D tangential breast radiation fields, the present doses to the coronary may be considerably less when modern techniques such as IMRT and VMAT are used in association with CT images for better target delineation. In order to study the possible involvement of fibrosis and apoptosis in this process, the presence of proc-I, TGF-b1, and caspase-3-cleaved were evaluated (Ferreira-Machado et al 2013). Female Wistar rats were given a single radiation dose of 15 Gy.…”

Section: Cardiotoxicity Induced By Radiotherapymentioning

confidence: 99%

Preliminary pre-clinical studies on the side effects of breast cancer treatment

Salata

deAlmeida

Ferreira-Machado

et al. 2021

International Journal of Radiation Biology

Self Cite

View full text Add to dashboard Cite

Purpose: Technological advancement in the treatment of cancer together with early detection and diagnosis have considerably improved the survival of breast cancer patients. On the other hand, the potential of patients developing side effects from cancer treatment are not negligible. Despite the progress that has been made in terms of early diagnosis, therapy, and survival, including improvements in the chemotherapeutic agents, radiation and molecular targeted therapies, cardiotoxicity of cancer therapy is still cause for concern. Radiation therapy for breast cancer is associated with increased risk of heart disease and myocardial infarction. Furthermore, the association of radiation therapy to chemotherapy is an important aspect to be considered in the development of cardiac disease, as this could play an additional role as a risk factor. Besides the heart effect, other side effects can be observed in the bone, ovary, uteri, and other organs. This paper aims to review the recent literature to present the current understanding of side effects associated with breast cancer treatment. The focus is on recent preclinical studies that have assessed potential changes in different organs that may be injured after breast cancer treatment, both due to both radiation and chemotherapy agents. Conclusion: Radiation-induced heart disease is one important side effect that must be considered during the treatment planning and patient follow-up. The cardiac damage can be potentialized when chemotherapy is associated to radiotherapy, and the literature findings indicate that heart fibrosis plays an important role at the radio-chemotherapy induced cardiac damage. Literature findings also showed important side effects at the bone, that can lead to ospeoporosis, due to the decrease of calcium, after radio or chemotherapy treatments. This decrease could be explained by the ovarian failure observed at rats after chemotherapy treatment. It is of great importance to acknowledge the complications originating from the treatment, so that new strategies can be developed. In this way, it will be possible to minimize side effects and improve the patients' quality of life.

show abstract

Caspase-3 activation and increased procollagen type I in irradiated hearts

Cited by 10 publications

References 31 publications

Radiation-Induced Alterations in Mitochondria of the Rat Heart

Radiation-Induced Alterations in Mitochondria of the Rat Heart

Alterations in Low-Z Elements Distribution in Heart Tissue after Treatments to Breast Cancer Using LEXRF Technique

Preliminary pre-clinical studies on the side effects of breast cancer treatment

Contact Info

Product

Resources

About