Short-term systemic effects of head and neck irradiation.
BACKGROUND
Various localized side effects which accompany head and neck irradiation [IR] have been widely reported. However, systemic side effects/have been only sparsely reported in the short-term period post-IR in an animal model. The potential modulatory role of zinc-desferrioxamine [Zn-DFO] on IR effects was examined because of its known ability to protect against the damage induced by free radicals which are mediated by redox-active metal ions.


METHODS
We used three groups of male Wistar rats: a] sham irradiated controls b] irradiated [15 Gy]; c] irradiated and treated with Zn-DFO [20 mg/k] one hour prior to IR. During the first two weeks post-IR, body weight and food and water intake were monitored daily, while lymphocytes, segmented neutrophils and white blood cells [WBC] were counted at 10 minutes 4 and 16 hours and 1, 3, 7 and 14 days. Serum TNF-a and IL-6 were obtained at 10 minutes and 7 days.


RESULTS
On day 7 post-IR, body weight and food and water intake were reduced by 84% 96% and 85% [p < 0.01], respectively in the above mentioned three groups of rats. This resulted in the death of 22% of the animals and was followed by recovery towards the end of the second week. At all time points examined between 10 minutes and 14 days, WBC were reduced by 52-74%. On the 7th day, Zn-DFO demonstrated a 33% protective effect against the WBC reduction. At 10 mins post-IR, a 84.8-fold [p < 0.01] increase of TNF-alpha, but not IL-6, was noted. However, on the 7th day post-IR, both TNF-alpha and IL-6 levels were increased by 48.5-fold and 102.5-fold [0.01], respectively.


CONCLUSIONS
The data presented delineate the severe short-term systemic effects of head and neck IR in a rat model. We suggest considering the severe cachectic and immunocompromised status of the animals when performing various short-term studies with this model. During this period nutritional and immunological support for the examined animals is recommended. Further evaluation of the underlying mechanisms of IR-induced leukopenia and cachexia in animals and the possible implications for humans is warranted.
Department of Oral & Maxillofacial Surgery, Rambam Medical Center, Haifa, Israel. nagler@tx.technion.ac.il
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D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism / Q000528:radiation effects; D003676:Deferoxamine / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects / Q000528:radiation effects; D004435:Eating / Q000187:drug effects / Q000528:radiation effects; D005609:Free Radicals / Q000378:metabolism; D006257:Head / Q000528:radiation effects*; D007958:Leukocyte Count / Q000528:radiation effects; D008297:Male; D009333:Neck / Q000528:radiation effects*; D009942:Organometallic Compounds / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D005609:Free Radicals; D009942:Organometallic Compounds; D011837:Radiation-Protective Agents; C086228:zinc-desferrioxamine; D003676:Deferoxamine