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Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol

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Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol

Auteurs : Marjan Boerma [États-Unis] ; Kerrey A. Roberto [États-Unis] ; Martin Hauer-Jensen [États-Unis]

Source :

International journal of radiation oncology, biology, physics [ 0360-3016 ] ; 2008.

RBID : PMC:2574608

Abstract

Purpose

Radiation-induced heart disease (RIHD) is a severe side effect of thoracic radiotherapy. This study examined the effects of PTX and α-tocopherol on cardiac injury in a rat model of RIHD.

Methods and Materials

Male Sprague-Dawley rats received fractionated local heart irradiation with a daily dose of 9 Gy for 5 days and were observed for six months after irradiation. Rats were treated with a combination of pentoxifylline (PTX, 100 mg/kg/day) and α-tocopherol (20 IU/kg/day) and received these compounds either from one week before until six months after irradiation or starting three months after irradiation, a time point at which histopathological changes become apparent in our model of RIHD.

Results

Radiation-induced increases in left ventricular diastolic pressure (in mmHg: 35 ± 6 after sham-irradiation, 82 ± 11 after irradiation) were significantly reduced by PTX and α-tocopherol (early treatment: 48 ± 7, late treatment: 53 ± 6). PTX and α-tocopherol significantly reduced deposition of collagen types I (radiation only: 3.5 ± 0.2 μm² per 100 μm², early treatment: 2.7 ± 0.8, late treatment: 2.2 ± 0.2) and III (radiation only: 13.9 ± 0.8, early treatment: 11.0 ± 1.2, late treatment: 10.6 ± 0.8). On the other hand, radiation-induced alterations in heart/body weight ratios, myocardial degeneration, left ventricular mast cell densities, and most echocardiographic parameters were not significantly altered by PTX and α-tocopherol.

Conclusions

treatment with PTX and α-tocopherol may have beneficial effects on radiation-induced myocardial fibrosis and left ventricular ex vivo function, both when started before irradiation and when started later during the process of RIHD.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574608

DOI: 10.1016/j.ijrobp.2008.04.042
PubMed: 18632215
PubMed Central: 2574608

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PMC:2574608

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<author><name sortKey="Boerma, Marjan" sort="Boerma, Marjan" uniqKey="Boerma M" first="Marjan" last="Boerma">Marjan Boerma</name>
<affiliation wicri:level="2"><nlm:aff id="A1"> Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America</nlm:aff>
<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Roberto, Kerrey A" sort="Roberto, Kerrey A" uniqKey="Roberto K" first="Kerrey A." last="Roberto">Kerrey A. Roberto</name>
<affiliation wicri:level="2"><nlm:aff id="A1"> Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America</nlm:aff>
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<front><div type="abstract" xml:lang="en"><sec id="S18"><title>Purpose</title>
<p id="P2">Radiation-induced heart disease (RIHD) is a severe side effect of thoracic radiotherapy. This study examined the effects of PTX and α-tocopherol on cardiac injury in a rat model of RIHD.</p>
</sec>
<sec sec-type="materials|methods" id="S19"><title>Methods and Materials</title>
<p id="P3">Male Sprague-Dawley rats received fractionated local heart irradiation with a daily dose of 9 Gy for 5 days and were observed for six months after irradiation. Rats were treated with a combination of pentoxifylline (PTX, 100 mg/kg/day) and α-tocopherol (20 IU/kg/day) and received these compounds either from one week before until six months after irradiation or starting three months after irradiation, a time point at which histopathological changes become apparent in our model of RIHD.</p>
</sec>
<sec id="S20"><title>Results</title>
<p id="P4">Radiation-induced increases in left ventricular diastolic pressure (in mmHg: 35 ± 6 after sham-irradiation, 82 ± 11 after irradiation) were significantly reduced by PTX and α-tocopherol (early treatment: 48 ± 7, late treatment: 53 ± 6). PTX and α-tocopherol significantly reduced deposition of collagen types I (radiation only: 3.5 ± 0.2 μm<sup>2</sup>
 per 100 μm<sup>2</sup>
, early treatment: 2.7 ± 0.8, late treatment: 2.2 ± 0.2) and III (radiation only: 13.9 ± 0.8, early treatment: 11.0 ± 1.2, late treatment: 10.6 ± 0.8). On the other hand, radiation-induced alterations in heart/body weight ratios, myocardial degeneration, left ventricular mast cell densities, and most echocardiographic parameters were not significantly altered by PTX and α-tocopherol.</p>
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<p id="P5">treatment with PTX and α-tocopherol may have beneficial effects on radiation-induced myocardial fibrosis and left ventricular <italic>ex vivo</italic>
 function, both when started before irradiation and when started later during the process of RIHD.</p>
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Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol

Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol

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