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Calcium antagonists protect mice against lethal doses of ionizing radiation

Department of Research, University Hospitals, Hebelstrasse 20, 4031 Basel, Switzerland

Currently available radioprotectors are poorly tolerated in man and the general use of aminothiol radioprotectors is compromised by their side-effects. In a search for less toxic radioprotective agents, diltiazem, a calcium antagonist with a

benzothiazepine structure, was found to protect mice against a lethal (LD₁₀₀) radiation dose allowing survival of up to 93%. Dihydropyridine calcium antagonists such as nifedipine, nimodipine, isradipine and nitrendipine also provided radioprotection. Calcium antagonists might attenuate radiation-induced injury by inhibiting cellular calcium overload, subsequent to cell: membrane damage caused by radiation-generated free radicals. In view of their good tolerance, calcium antagonists may be applied safely in situations of radiation exposure, including radiotherapy and internal radionuclide contamination. These calcium antagonists may also be viewed in other contexts where free radicals are implicated in pathological processes.

Key Words: Radioprotection • Calcium antagonists • Diltiazem • Nifedipine • Nimodipine

Received for publication October 28, 1991. Accepted for publication June 29, 1992.

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