Hydroxyl radicals have been implicated in various forms of tissue injury ranging from radiation-induced cell death to alloxan-induced diabetes in animals. Although hydroxyl radicals can be readily generated in vitro, for example by the action of radiation or from the reaction of ferrous (FeII) ions with peroxides, they have not been observed directly in vivo. Their involvement in tissue damage has generally only been inferred from studies with so-called selective radical scavengers. In this paper the validity of such inferences will be briefly discussed in the light of current knowledge about the mechanisms and rates of reactions of hydroxyl radicals with biological compounds.

Chemical Phenomena↗

PubMedDate not supplied

Iron, zinc, free radicals and oxygen in tissue disorders and cancer control.

Evidence is presented supporting the argument that various tissue disorders are the result of iron becoming decompartmentalized. In healthy cells, vital molecules are protected from the action of decompartmentalized iron by the presence of zinc. This protection is particularly important during processes leading to cell division. Should excessive decompartmentalization occur and this protective mechanism become overloaded or should it be weakened by ill health, damaging oxidative free-radical reactions may take place. If these are extensive, death may result. When they are only limited, possibly owing to a low oxygen tension or the presence of copper or a carcinogen, the cell may survive but cancer may result. This 'antioxidant' theory of cancer may provide a unifying mechanism for the action of many carcinogenic agents. Carcinogens are considered to be activated not only by the more usually accepted enzymic pathways but by free-radical reactions, catalysed by iron, in the vicinity of critical sites.

Cell Division↗

PubMedDate not supplied

Metronidazole (Flagyl), lactate and ethanol: enhancement of cytotoxic action and the effect of a dehydrogenase inhibitor and a drug metabolite.

The cytotoxicity of metronidazole towards CHO cells in culture has been found to be enhanced by the presence of lactate and ethanol. For 20 mM lactate the maximum enhancement was observed with 5 mM metronidazole. The enhancement by lactate was reduced by the additional presence of 5 mM oxamate (an LDH inhibitor) and 5 mM hydroxyethyl oxamate (a metronidazole metabolite). The cytotoxicity of 5 mM metronidazole was also enhanced by the presence of 30 mM ethanol. The results suggest an involvement of dehydrogenase enzyme systems in the hypoxic activation and toxicity of some nitroimidazoles.

Animals↗