Metalloporphyrin antioxidants ameliorate normal tissue radiation damage in rat brain.

Abstract:

PURPOSE:We examined the effects of manganese (III) meso-tetrakis (diethyl-2-5-imidazole) porphyrin, a metalloporphyrin antioxidant (MPA), on neural tissue radiation toxicity in vivo and on tumour cell radiosensitivity in vitro. MATERIALS AND METHODS:MPA was administered directly into the right lateral ventricle of young adult, male Sprague-Dawley rats (0 or 3.4 microg) 3 h before treatment with a single fraction, 100 Gy radiation dose delivered to the left brain hemisphere. The effects of treatment on radiation responses were assessed at different time points following irradiation. RESULTS:MPA treatment prior to brain irradiation protected against acute radiation-induced apoptosis and ameliorated delayed damage to the blood-brain barrier and radiation necrosis, but without producing a discernible increase in tissue superoxide disumtase (SOD) activity. In vitro, MPA pretreatment protected against radiation-induced apoptosis in primary neuronal cultures and increased clonogenic survival of irradiated rat glioma C6 cells, but had no discernible effect on radiation-induced DNA double-strand breaks. MPA, a low molecular weight SOD mimic, significantly increased mitochondrial SOD activity in C6 cells, but not total cellular SOD activity. MPA up-regulated C6 expression of heme-oxygenase 1 (HO-1), an endogenous radioprotectant, but had no effect on HO-1 levels in human astrocytoma U-251 cells, human prostatic carcinoma LNCaP cells, or primary rat brain microvascular endothelial cells in vitro, nor on brain tissue HO-1 expression levels in vivo. CONCLUSIONS:Metalloporphyrin antioxidants merit further exploration as adjunctive radioprotectants for cranial radiotherapy/radiosurgery applications, although the potential for tumour protection must be carefully considered.

journal_name

Int J Radiat Biol

authors

Pearlstein RD,Higuchi Y,Moldovan M,Johnson K,Fukuda S,Gridley DS,Crapo JD,Warner DS,Slater JM

doi

10.3109/09553000903419965

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

145-63

issue

2

eissn

0955-3002

issn

1362-3095

journal_volume

86

pub_type

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