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

Abstract

PURPOSE:

Radiation-induced heart disease (RIHD) is a severe side effect of thoracic radiotherapy. This study examined the effects of pentoxifylline (PTX) and alpha-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 6 months after irradiation. Rats were treated with a combination of PTX, 100 mg/kg/day, and alpha-tocopherol (20 IU/kg/day) and received these compounds either from 1 week before until 6 months after irradiation or starting 3 months after irradiation, a time point at which histopathologic changes become apparent in our model of RIHD.

RESULTS:

Radiation-induced increases in left ventricular diastolic pressure (in mm Hg: 35 +/- 6 after sham-irradiation, 82 +/- 11 after irradiation) were significantly reduced by PTX and alpha-tocopherol (early treatment: 48 +/- 7; late treatment: 53 +/- 6). PTX and alpha-tocopherol significantly reduced deposition of collagen types I (radiation only: 3.5 +/- 0.2 mum(2) per 100 mum(2); 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 alpha-tocopherol.

CONCLUSIONS:

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

• Authors: Marjan Boerma, Kerrey A Roberto, Martin Hauer-Jensen
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 72 Issue 1 Pg. 170-7 (Sep 01 2008) ISSN: 0360-3016 [Print] United States
• PMID: 18632215 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Collagen Type III
• Radiation-Protective Agents
• alpha-Tocopherol
• Pentoxifylline

Topics

• Animals
• Cell Count
• Collagen Type I (metabolism)
• Collagen Type III (metabolism)
• Cytoskeleton (radiation effects)
• Diastole
• Fibrosis
• Heart (radiation effects)
• Male
• Mast Cells (cytology, radiation effects)
• Myocardium (pathology)
• Pentoxifylline (therapeutic use)
• Radiation Injuries, Experimental (drug therapy, pathology, prevention & control)
• Radiation-Protective Agents (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• alpha-Tocopherol (therapeutic use)