Insecticides enzyme induction

There are several other interesting phenomena associated with metabolism, namely, synergism, antagonism, selective toxicity, enzyme induction, and resistance. It will be seen that all of these involve some modification of metabolic activity resulting in changing the toxicity of insecticides. 

Detoxification enzymes such as cytochrome P450 monooxygenases, glutathione S-transferases, and hydrolases play important roles in the metabolism of and resistance to insecticides in insects. These enzymes possess the capacity for rapid increases in activity in response to chemical stress, a phenomenon known as enzyme induction. Readers are referred to reviews by Terriere and Yu (1974), Terriere (1984), Brattsten (1979), Yu (1986a, 1996, 2001) and Feyereisen (2005) for discussion of work pertaining to induction of detoxification enzymes in insects. 

Drug metabolism may also be increased by hepatic enzyme induction from insecticide acciunu-lation, e.g. dicophane (DDT) and from alcohol and the tobacco habit, e.g. smokers require a higher dose of theophylline. 

Cumulative plots of carbofuran mineralization in a history and a nonhistory soil are presented in Figure 1. The initially accelerating rate of C02 production, indicative of a microbial response (e.g., enzyme induction, population growth), is characteristic of enhanced degradation. Comparison of the mineralization of u-carbonyl and 14C-ring labelled carbofuran demonstrates an important consideration in this type of assay the location of the u label in the insecticide is critical for this type of assay to provide useful information. Although the carbonyl C was almost completely evolved as CO2, the ring C was only slowly mineralized. 

Chlordane, like other organochlorine insecticides, functions as a potent inducer of hepatic microsomal enzymes. Induction of these enzymes following chlordane administration is associated... 

Kinoshita FK, Kempf CK. 1970. Quantitative measurement of hepatic microsomal enzyme induction after dietary intake of chlorinated hydrocarbon insecticides [Abstract]. Toxicol AppI Pharmacol 17 288. 

The extent of the enzyme induction depends on the drug and its dosage, but it may take days or even 2 to 3 weeks to develop fully, and may persist for a similar len h of time when the enzyme inducer is stopp. This means that enzyme induction interactions are delayed in onset and slow to resolve. Enzyme induction is a common mechanism of interaction and is not confined to drugs it is also caused by the ehlorinated hydrocarbon insecticides such as dicophane and lindane, and smoking tobacco. 

Once consumed, allelochemics have assorted deleterious effects. Otherwise, they can pass through the insect with no effect, be sequestered, or detoxified. Many enzyme systems are involved in biochemical defense against plant allelochemics, but the most familiar and perhaps most important are the mixed function oxidases. Brattsten (1979) describes the three major characteristics that contribute to their importance in biochemical waste disposal (i) they catalyze numerous oxidative reactions that produce more polar and hence more excretable compounds, (ii) they are non-specific in that a wide range of chemicals are acceptable substrates, (iii) they can adjust rapidly (within minutes) to the presence of allelochemics or synthetic insecticides via induction. The MFO detoxification system is not confined to insects MFO activity has been identified in a wide range of vertebrates and invertebrates. A variety of flies, mosquitoes, cockroaches, crickets and a minimum of 40 species of Lepidoptera (as well as representatives from other insect orders) possess MFO activity (review Brattsten, 1979). 

Subacute toxicity occurs when a sublethal dosage is encountered over a period of several days. Enzyme induction can enhance the toxicity of insecticides acquired during that time period. 

Microsomal Enzyme Induction - The activity of liver microsomal enzymes can be altered by nutritional factors, hormones, and many foreign compounds. Drugs, insecticides, and carcinogens are known to stimulate drug metabolizing enzymes and frequently to increase the concentration of enzyme protein (induction)... 

Yu SJ (1983) Induction of detoxifying enzymes by allelochemicals and host plants in the fall armyworm. Pestic Biochem Physiol 19 330-336 Yu SJ (1984) Interactions of allelochemicals with detoxification enzymes of insecticide-susceptible and resistant fall armyworms. Pestic Biochem Physiol 22 60-68 Yu SJ (1986) Consequences of induced foreign compound-metabolizing enzymes in insects. In Brattsten LB, Ahmad S (eds) Molecular aspects of insect-plant associations. Plenum, New York, pp 153-174... 

DuBois KP, Kinoshita FK. 1968. Influence of induction of hepatic microsomal enzymes by phenobarbital on toxicity of organic phosphate insecticides. Proc Soc Exp Biol Med 129 699-702. 

Mitotane, being closely related to the organochlo-rine insecticides, shares its inductive effects on the fiver microsomal drug-metabolizing enzyme system, and its use may therefore alter the requirement for concomitantly administered drugs that are also metabolized by this pathway. 

In the early 1960s, during investigations on the N-demethylation of aminoazo dyes, it was observed that pretreatment of mammals with the substrate or, more remarkably, with other xenobiotics, caused an increase in the ability of the animal to metabolize these dyes. It was subsequently shown that this effect was due to an increase in the microsomal enzymes involved. A symposium in 1965 and a landmark review by Conney in 1967 established the importance of induction in xenobiotic interactions. Since then, it has become clear that this phenomenon is widespread and nonspecific. Several hundred compounds of diverse chemical structure have been shown to induce monooxygenases and other enzymes. These compounds include drugs, insecticides, polycyclic hydrocarbons, and many others the only obvious common denominator... 

The importance of the cytochrome P450 monooxygenases, glutathione S-transferases, car-boxylesterases, and epoxide hydrolases in insecticide metabolism and detoxification, as well as in insecticide resistance, is well documented. It is, therefore, logical to expect that an increase in these enzyme activities resulting from induction by xenobiotics would decrease the toxicity of an insecticide because of enhanced metabolism (see review by Yu, 1986a). 

---