Metabolic Interactions of Pesticides - Pesticide Biotransformation and Disposition - page 164

Table 7.3 Inhibition of Human Hepatic Phase I Metabolism by Pesticides
Substrate

Enzyme Inhibitor(s) Reference

XENOBIOTIC SUBSTRATES
Carbaryl Liver microsomes Chlorpyrifos Tang et al. (2002)

Carbaryl CYP2B6 Chlorpyrifos Tang et al. (2002)

Carbofuran Liver microsomes Chlorpyrifos Usmani et al. (2004)

DEET Liver microsomes Chlorpyrifos Usmani et al. (2002)

Fipronil Liver microsomes Chlorpyrifos Joo et al. (2007)

Fipronil CYP3A4 Chlorpyrifos Joo et al. (2007)

Imipramine Liver microsomes Chlorpyrifos,

azinphosphos methyl,
parathion

Di Consiglio (2005)

Imipramine CYPs 1A2, 3A4,

2C19

Chlorpyrifos,
azinphosphos methyl,
parathion

Di Consiglio (2005)

Nonane Liver microsomes Chlorpyrifos Joo et al. (2007)

Nonane CYP2B6 Chlorpyrifos Joo et al. (2007)

ENDOGENOUS SUBSTRATES
Estradiol

Liver microsomes Chlorpyrifos, fonofos,

carbaryl, naphthalene

Usmani et al. (2006)

Estradiol CYP1A2 Chlorpyrifos, fonofos,

carbaryl, naphthalene

Usmani et al. (2006)

Estradiol CYP3A4 Chlorpyrifos, fonofos,

deltamethrin, permethrin

Usmani et al. (2006)

Testosterone Liver microsomes Methoxychlor Li et al., 1993

Testosterone Liver microsomes Chlorpyrifos, phorate,

fonofos

Usmani et al. (2003)

Testosterone CYP3A4 Chlorpyrifos Usmani et al. (2003)

Testosterone CYP Fipronil Tang et al. (2004)

accompanied by loss of CYP as detected by measurement of the dithionite-reduced
CO complex as well as loss of monooxygenase activity ( Berger and Sultatos, 1996;
Butler and Murray, 1993; Neal, 1985; Neal and Halpert, 1982; Neal et al., 1983 ).
Cohen (1984) showed that acetaminophen toxicity was reduced by the organophos-
phorus insecticide fenitrothion, as a result of inhibition of the CYP-dependent activation
of acetaminophen. Studies with purified CYP isoforms and fenitrothion demonstrated
that the amount of inhibition varied with the CYP isoform ( Levi et al., 1988 ). Other
OPs, known to be CYP inhibitors, affect the distribution of neonicotinoids in the
brain and, to a lesser extent, in the liver ( Shi et al., 2009 ).
In human liver microsomes, metabolism of parathion resulted in a concurrent loss
of total CYP as well as the loss of several CYP-mediated enzyme activities ( Butler