Piperonyl butoxide, effect

Bates, Hewlett, and Lloyd (I) found that both piperonyl butoxide and SKF 525A, the ester of 2-diethylaminoethyl 2,2-diphenyl-w-pentanoate, synergized the action of pyrethrins on insects of species of the lesser mealworm beetles and houseflies but both antagonized the action of malathion. SKF 525A is known to increase the effects on mammals of drugs of various types and has been shown to synergize pyrethrins. 

Bates, Hewlett, and Lloyd (2) therefore studied the synergistic effects of some compounds related to 2-diethylaminoethyl 2,2-diphenyl-w-pentanoate on the insecticidal activity of pyrethrins. They found active compounds when a 2-diethylamino moiety was joined to the diphenylmethyl moiety through an ester, ketone, or ether linkage. However, none of the compounds investigated approached piperonyl butoxide in synergistic activity with pyrethrins. 

Piperonyl butoxide, a common potentiator of insecticide effects that inhibits microsomal enzymes, antagonized the toxic effects of methyl parathion in mice (Mirer et al. 1977). 

Isshiki K, Miyata K, Martsui S, et al. 1983. [Effects of post-harvest fungicides and piperonyl butoxide on the acute toxicity of pesticides in mice. Safety evaluation for intake of food additives. III]. 

A striking illustration of the effect of chemical structure on insecticidal properties is provided by the data given in this paper on compounds related to piperonyl butoxide. According to the above theory, the methylenedioxyphenyl nucleus present in this substance is the toxophore. The materials selected for comparison show the reduction in toxicity produced, first, by modifying the toxophore, and, second, by substituting different groups for the auxotox radical. 

Methylenedioxy compounds such as piperonyl butoxide are used to make insecticides more effective by inhibiting the insect enzymes that inactivate the insecticide (Fig. 8.21). Some drugs such as paroxetine and 3,4-methylenedioxymethamphetamine (ecstasy) also contain this functional group. 

In an effort to characterize further the metabolism of DEHP by trout, the effect of the mixed function oxidase inhibitor, piperonyl butoxide, upon the metabolism of DEHP by these trout liver fractions and serum was examined. Because of the use of piperonyl butoxide as an insecticide synergist, it is possible that fish might be exposed to this chemical in the environment. The data in Table VII show that piperonyl butoxide inhibited overall metabolism of DEHP by liver homogenates and microsomes whether NADPH was added or not. The hydrolysis of DEHP by serum was also blocked by piperonyl butoxide and although not shown, this was also the case with liver cytosol. These latter results were surprising because piperonyl butoxide has been known as a mixed function oxidase inhibitor only, and would not be expected... 

Effect of Piperonyl Butoxide on Metabolism of C-di-2-ethylhexyl Phthalate by Rainbow Trout Liver Preparations and Blood Seruma... 

In additional in vitro studies with a number of methylene-dioxyphenyl compounds, only tropital, in addition to piperonyl butoxide, had similar inhibitory effects on the metabolism of DEHP by trout liver homogenates and serum (16). Of the methyl-enedioxyphenyl compounds studied, only tropital had a long side chain like that of piperonyl butoxide. This suggests that similarities in the side chains of these two compounds and the side chains of DEHP and 2,4-dichlorophenoxyacetic acid-n-butyl ester may be responsible for this inhibition. 

Effect of Piperonyl Butoxide (lmg/1) on Tissue Levels on C from - C-di-2-ethylhexyl Phthalate in Rainbow Trout in vivo... 

J7, Effect of Piperonyl Butoxide on Disposition of Di-2-EthyIhexyl Phthalate by Rainbow Trout, 633-640. 

L14. Lucier, G. W., McDaniel, O. S., and Matthews, H. B., Microsomal rat liver UDP glucuronyltransferase. Effects of piperonyl butoxide and other factors on enzyme activity. Arch. Biochem. Biophys. 145, 520-530 (1971). 

Several studies have been conducted to assess factors which influence the toxicity of hexachlorobutadiene. Most of these studies have involved effects of mixed function oxidase activity (MFO) on renal toxicity. The administration of MFO inhibitors including SKF-525A (Lock and Ishmael 1981) and piperonyl butoxide (Davis 1984 Hook et al. 1982) did not alter... 

Use of piperonyl butoxide, a potent cytochrome P-450 inhibitor, has been recommended as an effective means for preventing the degradation of chloramphenicol. Since addition of this substance to liver homogenates could result in a recovery enhancement from about 30% to 60%, it was suggested that incurred tissue samples taken for analysis should be frozen immediately after excision and homogenized in water containing 2.5% piperonyl butoxide (11). 

Recently, the stability of chloramphenicol in both spiked and incurred calf tissues has been further investigated (14). The same favorable effect of piperonyl butoxide on the stability of chloramphenicol has been observed in both liver and kidney tissues. Moreover, the stability of chloramphenicol in these organs was... 

Inhalation exposure of male B6C3Fi mice to dichloromethane (6 h, once) led to vacuolation of bronchiolar cells at exposure levels > 2000 ppm [6940 mg/m ], while no effect was obsened at levels < 1000 ppm [3470 mg/m (Foster et al., 1994). Pretreatment with the cytochrome P450 inhibitor piperonyl butoxide (300 mg/kg intraperi-toneally) 1 h before the exposure practically abolished the toxic effect upon bronchiolar cells, while buthionine sulfoximine (1 g/kg intraperitoneally), which decreased the pulmonary glutathione content by 50%, had no such protective effect. In Clara cells isolated after exposure to dichloromethane exposure (> 1000 ppm), the proportion of cells in tlie S-phase was increased. 

Methylenedioxy (Benzodioxole) Ring Cleavage. Methylenedioxy-phenyl compounds, such as safrole or the insecticide synergist, piperonyl butoxide, many of which are effective inhibitors of CYP monooxygenations, are themselves metabolized to catechols. The most probable mechanism appears to be an attack on the methylene carbon, followed by elimination of water to yield a carbene. The highly reactive carbene either reacts with the heme iron to form a CYP-inhibitory complex or breaks down to yield the catechol (Figure 7.8). 

Studies of antipyrine metabolism may be used to illustrate the effect of inhibition on metabolism in vivo in addition, these studies have demonstrated variation among species in the inhibition of the metabolism of xenobiotics. In the rat, a dose of piperonyl butoxide of at least 100 mg/kg was necessary to inhibit antipyrine metabolism, whereas in the mouse a single intraperitoneal (IP) or oral dose of 1 mg/kg produced a significant inhibition. In humans an oral dose of 0.71 mg/kg had no discernible effect on the metabolism of antipyrine. 

Irreversible inhibition, which is much more important toxicologically, can arise from various causes. In most cases the formation of covalent or other stable bonds or the disruption of the enzyme structure is involved. In these cases the effect cannot be readily reversed in vitro by either dialysis or dilution. The formation of stable inhibitory complexes may involve the prior formation of a reactive intermediate that then interacts with the enzyme. An excellent example of this type of inhibition is the effect of the insecticide synergist piperonyl butoxide (Figure 9.6) on hepatic microsomal monooxygenase activity. This methylenedioxyphenyl compound can form a stable inhibitory complex that blocks CO binding to P450 and also prevents substrate oxidation. This complex results from the formation of a reactive intermediate, which is shown by the fact that the type of inhibition changes from competitive to irreversible as metabolism, in the... 

Successive resistances have driven control of the Boophilus cattle ticks all the way to OP compounds, and from them to chlor-phenamidine (chlordimeform) although it has been recently found that carbaryl is effective in cattle dips if synergized with piperonyl butoxide. The two-spotted mite has gone through a fantastic sequence of acaricides, the only ones to which resistance has not yet been reported being Pentac and the organo-tin compound Plictran. 

Amweg EL. 2006. Effect of piperonyl butoxide on permethrin toxicity in the amphipod Hyalella azteca. Environ Toxicol Chem 25 1817-1825. 

Kumar, S., Thomas, A., Sahgal, A., Verma, A., Samuel, T., and Phillai, M.K.K., Effect of the synergist, piperonyl butoxide, on the development of deltamethrin resistance in yellow fever mosquito, Aedes aegypti L. (Diptera Culicidae), Arch. Insert Biochem. Physiol., 50,1, 2002. 

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