Piperonyl Butoxide with Cytochrome

Hodgson, E. and Levi., P.E., Interactions of piperonyl butoxide with cytochrome P450, in Piperonyl butoxide, the insecticide synergist, Jones, D.G., Ed., San Diego Academic Press, 1998, p. 41. 

Interactions of Piperonyl Butoxide with Cytochrome P450... 

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. 

Figure 3.2. 13 i phasic effect of piperonyl butoxide on mouse hepatic cytochrome P45t> activities (from Kinsler et af. 1990, with permission). 

There are a number of well known inhibitors of cytochromes P-450 which form stable complexes with the enzyme. Thus SKF 525A, piperonyl butoxide, triacetyloleandomycin, amphetamine, isoniazid and cimetidine are a few of those known to form complexes with cytochromes P-450. In the case of several of these inhibitors, metabolism catalysed by cytochromes P-450 takes place and the metabolite so produced inhibits the enzyme. Thus, amphetamine is believed to be metabolized to a nitroso intermediate which complexes with the enzyme. Piperonyl butoxide is a commonly used microsomal enzyme inhibitor. It is active both in vivo and in vitro,... 

Many chemicals are known to inhibit the metabolism of xenobiotics. Pyrazole, piperonyl butoxide, SKF-525A or cobaltous chloride pretreatments (inhibitors of cytochrome P-450 catalyzed metabolism) decrease the jri vitro alkylation both in rat liver and lung microsomes by IPO(IO). Correspondingly, pretreatment of rats with these compounds also decreases the tissue alkylation and toxicity of IPO in vivo(21). 

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