Induction of Detoxification Enzymes

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. 

Compound 1 Percentage in diet Aldrin epoxidase (nmol/min/mg protein) Cytochrome450 (nmol/mg protein) 

Groups of newly molted sixth-instar larvae were fed artificial diets containing the compounds for 2.5 days prior to enzyme assays. 

Source From Yu, S.J. et al., Pestic. Biochcm. Physiol, 12, 280,1979. With permission. 

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STAACK R, KINGSTON s, WALLiG M A and JEFFERY E H (1998) A Comparison of the individual and collective effects of four glucosinolate breakdown products from Brussels sprouts on induction of detoxification enzymes , Toxicol Appl Pharmacol, 149 17-23. 

Figure 9.17 Simplified model for induction of detoxification enzymes.

Yu, S.J., Induction of detoxification enzymes by triazine herbicides in the fall army worm, Spodoptem frugiperda (J. E. Smith), Pestic. Biochem. Physiol., 80,113, 2004. 

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... 

Metabolism also plays a critical role in the pharmacology of cocaine. The rapid hydrolysis of cocaine via two different pathways leads to its rapid inactivation/detoxification. This rapid metabolism has been a major determinant in the methods and modes of cocaine abuse. Identification and characterization of these hydrolytic enzymes would be useful in that selective induction of these enzymes offers a potential treatment strategy for dealing with cocaine overdose. It is conceivable that long-term elevation of the enzyme or enzymatic activity could be used in conjunction with maintenance therapy for cocaine addicts. Hydrolases or esterases are also responsible for the transesterfication of cocaine. The pharmacological effect of cocaine is prolonged and enhanced when cocaine is used in conjunction with ethanol. A carboxylesterase catalyzes an ethyl transeterification of cocaine to cocaethylene, which is biologically active. 

Isothiocyanates are potent inducers of Phase II detoxification enzymes, such as quinone reductase and glutathione transferase (Faulkner et al. 1998 Fahey and Talalay 1999 Rose et al. 2000 Basten et al. 2002 Munday and Munday 2004). The induction of these enzymes enables the excretion of potential carcinogens prior to harmftil effects and is thought to be an effective mechanism to reduce the risk of carcinogenesis. The mechanism by which this occurs is likely to be by the activation of the transcription factors Nrl2. Upon exposure to... 

Thus, exposure to any of these enzyme inducers concurrent with or after exposure to diazinon may result in accelerated bioactivation to the more potent anticholinesterase diazoxon. The extent of toxicity mediated by this phenomenon is dependent on how fast diazoxon is hydrolyzed to less toxic metabolites, a process that is also accelerated by the enzyme induction. Similarly, concurrent exposure to diazinon and MFO enzyme-inhibiting substances (e.g., carbon monoxide ethylisocyanide SKF 525A, halogenated alkanes, such as CC14 alkenes, such as vinyl chloride and allelic and acetylenic derivatives) may increase the toxicity of diazinon by decreasing the rate of the hydrolytic dealkylation and hydrolysis of both parent diazinon and activated diazinon (diazoxon) (Williams and Burson 1985). The balance between activation and detoxification determines the biological significance of these chemical interactions with diazinon. 

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