Malonaldehyde toxicity

Chemical Basis of Toxicity There is only one comprehensive theory for the action of ozone on biologic organisms—the theory of Chow and Tappel that the initial event is the formation of lipid peroxide and that successive events are an attempt to detoxify this product. The theory was developed from experiments with animals that showed that exposure to ozone increases malonaldehyde, gluthathione peroxidase, glutathione reductase, and G-6-PD ... 

Localization of double bonds in unknown compounds has frequently been determined by ozonolysis. Unsaturated fatty acids of biological membranes are susceptible to ozone attack, but there are some important differences from autoxidation reactions. These include the fact that malonaldehyde is produced from linoleate by ozonolysis (53) but not autoxidation and also that ozonolysis does not cause double bond conjugation as judged by absorption at 233 nm (52). Reactions with the polyunsaturated fatty acids produce several possibilities for toxic reactions direct disruption of membrane integrity and toxic reactions caused by fatty acid hydroperoxides, hydrogen peroxide, and malonaldehyde. 

Experiments in vitro are consistent with some of the chemical investigations. Enzymes are readily inactivated by ozone, and the inactivation can be traced to the more susceptible amino acid residues (Table XI). Reactions with unsaturated fatty acids have been examined, and the production of malonaldehyde and hydrogen peroxide has been detected (52-54). The lipid products have not been analyzed, and the toxicity of such products is yet to be determined. 

Several reports of the effects of ozone in vivo are presented in Table XII. It is impossible to decide whether the effects of ozone are primary reactions or the result of a series of reactions initiated by ozone. All results can be rationalized as enzyme inhibition of one sort or another. Effects on membrane structure are harder to observe, and in one case it was reported that the malonaldehyde which would be expected on fatty acid ozonolysis was only observed after symptoms were apparent (74). Results of electron microscope examination showed that the first observable damage was in the stroma of the chloroplasts (70). One can easily argue that earlier damage could not be detected by microscopic techniques. However, recent reports that the chloroplast polyribosomes are much more susceptible to degradation by ozone are important observations which are consistent with the microscopy experiments (76). Chloroplast polysomes are also more susceptible to sulfhydryl reagents than are cytoplasmic polysomes (77). This evidence indicates that ozone itself, or a toxic product from primary oxidation, can pass through the cytoplasm and have its effect in the chloroplast. 

Copper-containing intrauterine contraceptive devices (10-12) became popular because local inflammatory reactions in the endometrium are more marked and the contraceptive effect is thus more pronounced (SEDA-21, 234) (13). In addition, copper ions released from intrauterine contraceptive devices reach concentrations in the luminal fluids of the genital tract that are toxic to spermatozoa and embryos. The ability of copper to induce the generation of free radicals and the formation of malonaldehyde may be involved in its contraceptive effect. 

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