Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation

DNA damage induced by low doses of ionizing radiation causes apoptosis, whi ch is partially mediated via the generation of free radicals. Both free rad icals and apoptosis are involved in the majority of brain diseases, includi ng stroke, Alzheimer's disease and amyotrophic lateral sclerosis. Because p revious studies have shown that tetracycline derivatives doxycycline and mi nocycline have anti-inflammatory effects and are protective against brain i schemia, we studied whether minocycline and doxycycline or ceftriaxone, a c ephalosporin antibiotic with the potential to inhibit excitotoxicity, prote ct neurons against ionizing radiation in primary cortical cultures. A singl e dose of 1 Gy significantly increased lactate dehydrogenase release, induc ed DNA fragmentation in neurons and triggered microglial proliferation. Tre atment with minocycline (20 nm), doxycycline (20 nm) and ceftriaxone (1 mum ) significantly reduced irradiation-induced lactate dehydrogenase release a nd DNA fragmentation. The most efficient protection was achieved by minocyc line treatment, which also inhibited the irradiation-induced increase in mi croglial cell number. Our results suggest that some tetracycline derivative s, such as doxycycline and minocycline, and ceftriaxone, a cephalosporin de rivative, protect neurons against apoptotic death.