In Vitro Screening Of The Effect Of Hydrazine Derivatives On Hepatic Aryl Hydrocarbon Hydroxylase Activity
Authors: Al-Turk, WA; Raha, CR; Murray, WJ; Heinicke, RJ
HERO ID: 4240422
The effects of 14 hydrazine derivatives on hepatic microsomal arylhydrocarbon-hydroxylase (AHH) activity . . .
The effects of 14 hydrazine derivatives on hepatic microsomal arylhydrocarbon-hydroxylase (AHH) activity were studied in-vitro. The following compounds were tested at 0, 0.1, 2, 3, or 4 millimolar (mM): hydrazine-hydrate (7803578) (HH); methylhydrazine (60344) (MH); 1,1-dimethylhydrazine (57147) (1,1-DMH); 1-methyl-1-formylhydrazine (MFH); 1-propyl-1-formylhydrazine (PFH); 1,1-dipropylhydrazine (1,1-DPH); 1,1-diallylhydrazine (1,1-DAH); 1,1-dibutylhydrazine (1,1-DBH); 1,2-dimethylhydrazine (540738) (1,2-DMH); 1,2-diallylhydrazine (1,2-DAH); 1,2-dibutylhydrazine (1,2-DBH); phenylhydrazine (PH); 1-acetyl-2-p-(hydroxy-methyl)-phenylhydrazine (AHMPH); and 1-gamma-glutamyl-2-p-(hydroxy-methyl)-phenylhydrazine (GHMPH). Fresh liver microsomes were obtained from Sprague-Dawley-rats and incubated with the hydrazines at 0 to 4 millimolar (mM) in trisodium-isocitrate, magnesium-chloride, isocitrate-dehydrogenase, and benzo(a)pyrene; AHH activity was assayed spectrophotofluorometrically. At 0.1mM, significant decreases in AHH activity were seen for 1,1-DMH; 1,1-DAH; 1,1-DBH; and PH. At 1mM, significant decreases were seen for HH; MFH; PFH; 1,1-DPH; 1,2-DAH; 1,2-DBH; AHMPH; and GHMPH. Significant decreases were seen for 1,2-DMH at 2mM and MH at 4mM. PH was the most potent compound tested, with 85 percent inhibition at 0.1mM. The authors conclude that all the hydrazine derivatives tested inhibit hepatic AHH activity; the degree of inhibition is dependent on concentration and structure.