Increased Detoxification

A number of detoxification enzymes have been shown to be involved in resistance in insects. They are the cytochrome P450 monooxygenases, hydrolases, and glutathione S-transferases (GSTs). 

Resistance to insecticides can be due to enhanced oxidative metabolism caused by cytochrome P450 monooxygenases. This type of resistance usually results in producing less toxic metabolites. Even when the metabolites are more toxic, often resistance prevails, perhaps because the toxic metabolites are less stable, cannot reach the site of action due to change in polarity, or are neutralized by other factors. As we have already seen (Chapter 8), the cytochrome P450 enzyme system is rather nonspecific in its attack on organic compounds. Hence, this resistance factor is nonspecific, explaining much of the cross-resistance observed. 

Sequestration in insects This is another resistance mechanism in which GSTs were found to be involved in pyrethroid resistance. Kostaropoulos et al. (2001) have reported that GST confers protection against deltamethrin by binding to the insecticide in the yellow mealworm ijenebrio monitor). 

Carboxylesterases are involved in resistance to ester-containing insecticides such as organophosphate, carbamate, and pyrethroid insecticides. Resistance to organophosphate insecticides caused by enhanced carboxylesterase activity has been demonstrated in numerous insects and mites, including the mosquito (Cidex tarsalis, Culex pipiens, and 

Aphid strain Resistance factor to dimethoate Paraoxon hydrolyzed (pmol/mg aphid/hr) 

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Increasingly, detoxification is being done on an ambulatory basis, which is much less costly than inpatient detoxification (Hayashida et al. 1989). Inpatient detoxification is indicated for patients with serious medical or surgical illness and for those with a past history of adverse withdrawal reactions or with current evidence of more serious withdrawal reactions (e.g., dehrium tremens) (Feldman et al. 1975). 

Those that alter the metabolism of the carcinogen, causing decreased activation or increased detoxification... 

Results in Table 4 proved that the Grinization complex is highly effective in increasing detoxification function of the fiver. 

Burnet, M.W.M., B.R. Loveys, J.A. M. Holtum, and S.B. Powles (1993). Increased detoxification is a mechanism of simazine resistance in Lolium rigidum. Pestic. Biochem. Physiol., 46 207-218. 

Among the biochemical mechanisms of fungicide resistance are reduced permeability, metabolism (increased detoxification or decreased conversion to the toxic material), and reduced affinity of the target site for the toxin. 

Kennaugh, L. Pearce, D.. Daly. J.C. and Hobbes, A.A. (1993). A PRO syncrgisable resistance to permethrin in Helicitverpo armigera which is not due to increased detoxification by cytochrome P450. /V.tffC. tiiochem. Physiol. 45. 234-241. 

Resistance to pesticides arises primarily through changes in the sensitivity of the site of action or in the metabolism of the pesticide (25,27.28). Many pesticides are activated metabolically. While it is theoretically possible to generate resistance through reduced activation, it seems much more common to observe increased detoxification in resistant strains. In some cases decreased uptake or enhanced excretion also contribute. It is an obvious prerequisite for any type of scientifically-based attempt to combat resistance that the resistance mechanism and its genetic basis must be defined. 

Metabolic resistance mechanisms are still the most widely encountered causes for OP and carbamate resistance. Yet, after the first few cases of target site insensitivity were reported in the early 1970 s in mites and ticks, many such cases have been found also in insects. Resistance can also be enhanced by a decreased rate of penetration through the integument. This resistance mechanism by itself is of minor importance, but provides an increased opportunity for detoxification. A 50-fold increase in resistance to carbaryl was seen in a house fly strain, in which a gene for reduced penetration had been combined (by selective breeding) with a gene for increased detoxification (5). 

The inhibition of skin carcinogenesis by rosemary and its constituents, camosol and ursolic acid, has been demonstrated by Huang et al. (/). Furthermore, the suppression of rat mammary tumorigenesis induced by DMBA has been demonstrated by Singletary et al. (29). Meanwhile, the formation of mammary DMBA-DNA adducts in vivo was dose-dependently inhibited by camosol and ursolic acid (29). Rosemary components have the potential to decrease activation and increase detoxification of benzo(a)pyrene, identifying them as promising chemopreventive agents (30). 

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