Table 3.
Inhibitory constants for DIM with trout, rat and human CYPS.
| Species | Enzyme source (Inducer) | Activity (CYP selectivity) | Inhibition constant (μM) | Type of inhibition | References |
|---|---|---|---|---|---|
| Trout | Liver microsomes (BNF)a | ERODk (CYP1A1) | Kis= 2.7 ± 0.5 Kii = 14 ± 2.2 |
Non-competitive | (111) |
| Rat | Liver microsomes (BNF)b | EROD (CYP1A1) | Ki = 2.2 ± 0.2 | Competitive | (111) |
| Rat | Liver microsomes (PB)c | PRODl (CYP2B1) | Kis = 0.62 ± 0.08 Kii = 1.2 ± 0.60 |
Non-competitive | (111) |
| Rat | Liver microsomes (BNF)d | EROD (CYP1A1) | Ki = 1.60 ± 0.31 Kiu = 22.0 ± 6.2 |
Competitive Uncompetitive |
(112) |
| Rat | Liver microsomes (PB)e | PROD (CYP2B1) | Ki = 0.36 ± 0.09 Kiu = 0.60 ± 0.12 |
Competitive Uncompetitive |
(112) |
| Rat | Liver microsomes (PB)e | BRODm (CYP3A4) | Kiu = 0.47 ± 0.02 | Uncompetitive | (112) |
| Rat | Liver microsomes (BNF)b | AFB1-8,9-E (CYP1A2 & 3A4)n |
Kis= 137 ± 43 Kii = 58 ± 11 |
Non-competitive | (111) |
| Rat | Liver microsomes (BNF)b | AFM1 (CYP1A)o | Ki = 128 ± 24 | Competitive | (111) |
| Human | Expressed 1A1f | EROD (CYP1A1) |
Kis = 7.4 ± 2.0 Kii = 13 ± 2.7 |
Non-competitive | 143 |
| Human | Expressed 1A2g | Acetanilide-4-OH (CYP1A2) | Ki = 7.6 ± 4.1 | Competitive | (113) |
| Human | Expressed 1A1h | EROD (CYP1A1) | IC50 = 21.4 | – | (113) |
| Human | Expressed 1A2i | MRODp (CYP1A2) | IC50 = 40.9 | – | (113) |
| Human | Expressed 3A4j | BROD (CYP3A4) | IC50 = 14.5 | – | (113) |
Adult (200-300 g) rainbow trout fed 700 ppm β-naphthoflavone (BNF) for 7 days.
Male Fischer 344 rats injected ip daily for 4 days with 40 mg/kg BNF in corn oil.
Male Fischer 344 rats administered 0.1% phenobarbital (PB) for 7 days in drinking water.
Female Sprague-Dawley rats gavaged with 40 mg/kg BNF daily for 4 days.
Female Sprague-Dawley rats injected ip with 75 mg/kg PB daily for 4 days.
Microsomes from a human lymphoblastoid cell line (Gentest (Woburn, MA) with expressed recombinant human CYP1A1.
Microsomes from a human lymphoblastoid cell line (Gentest (Woburn, MA) with expressed recombinant human CYP1A2.
Microsomes from yeast (Gentest (Woburn, MA) expressing recombinant humans CYP1A1.
Microsomes from yeast (Gentest (Woburn, MA) expressing recombinant humans CYP1A2.
Supersomes (Gentest (Woburn, MA) expressing recombinant humans CYP3A4.
Ethoxyresorufin-O-deethylase.
Pentoxyresorufin-O-depentylase.
Benzyloxy-O-debenzylase.
Aflatoxin B1-epoxygenation with glutathione trapping.
Aflatoxin B1-4-hydroxylation.
Methyoxyresorufin-O-demethylase.