Oxidation selective toxicity

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

OPTIMISATION OF REACTOR TECHNOLOGY FOR SELECTIVE OXIDATION OF TOXIC ORGANIC POLLUTANTS IN WASTEWATER BY OZONE 255... 

Pretreatment process, focused on the selective oxidation of toxic pollutants which may disturb the biodegradation of the non toxic organic pollutants... 

Fukami, J-I., Shishido, T., Fukunaga, K. and Casida, J.E. Oxidative metabolism of rotenone in mammals, fish and insects and its relation to selective toxicity. J. Agr. Food. Chem. 

A consequence of this arsenite release is that a compound such as 3,4-dihydroxybutylarsonic acid may be selectively toxic to cells that can take it up. The compound itself is fairly harmless. Delivery of such compounds into cells and their subsequent oxidation inside the cell will result in release of arsenite. The arsenite may then kill the cell by inactivating enzymes that contain dihydrolipoyl groups (Section III,A). The other product formed when arsenite is released, a vinyl ketone, is a strong electrophile, and hence may also be toxic. 

Hydrolytic reactions. There are numerous different esterases responsible for the hydrolysis of esters and amides, and they occur in most species. However, the activity may vary considerably between species. For example, the insecticide malathion owes its selective toxicity to this difference. In mammals, the major route of metabolism is hydrolysis to the dicarboxylic acid, whereas in insects it is oxidation to malaoxon (Fig. 5.12). Malaoxon is a very potent cholinesterase inhibitor, and its insecticidal action is probably due to this property. The hydrolysis product has a low mammalian toxicity (see chap. 7). 

The onset of symptoms depends on the particular organophosphorus compound, but is usually relatively rapid, occurring within a few minutes to a few hours, and the symptoms may last for several days. This depends on the metabolism and distribution of the particular compound and factors such as lipophilicity. Some of the organophosphorus insecticides such as malathion, for example (chap. 5, Fig. 12), are metabolized in mammals mainly by hydrolysis to polar metabolites, which are readily excreted, whereas in the insect, oxidative metabolism occurs, which produces the cholinesterase inhibitor. Metabolic differences between the target and nontarget species are exploited to maximize the selective toxicity. Consequently, malathion has a low toxicity to mammals such as the rat in which the LD50 is about 10 g kg-1. 

It therefore appears that neurons in the substantia nigra might ultimately be destroyed because genetic factors lead to neuronal protein accumulation and free radical-induced oxidative stress that causes the degeneration and death of these neurons. As indicated earlier, however, the influence of environmental factors should be considered.49,64 It has been theorized, for example, that environmental toxins (e.g., herbicides, insecticides, fungicides) accelerate the neuronal destruction in people with Parkinson disease.14 Much of this evidence is based on the finding that a compound known as l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) appears to be selectively toxic to these neurons and can invoke parkinsonism in primates.84... 

In the mid-1960s we showed firstly that the natural tolerance of houseflies to cyclodienes resulted mainly from oxidative detoxication (33 55) and secondly that another enzyme system, epoxide hydrase, converted certain dieldrin analogues into the corresponding trans-diols, (56,57) Interspecific differences in ability to attack enzymatically the unchlorinated ring systems of various analogues, either oxidatively and/or hydratively (if appropriate) can confer selective toxicity between insect species and also between insects and mammals (58) ... 

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