Renal metabolism of formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazide.
Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazide (FNT) is a potent renal carcinogen in the rat. This study assessed the metabolism of FNT by the isolated perfused rat kidney and whole rat. The glomerular filtration rate and the fractional excretion of sodium for the isolated perfused kidney indicated that under the conditions of these experiments FNT did not alter these renal parameters. The half-life (t1/2) for FNT in the isolated perfused kidney was 67 +/- 8 min. Using HPLC, a metabolite of FNT was observed in urine from the isolated perfused kidney. This metabolite had absorbance at 385 nm but not 254 nm and could not be detected electrochemically at +500 mV. While the excretion of FNT decreased with time of perfusion, the metabolite excretion increased. Whole animal studies demonstrated that FNT is rapidly cleared from blood within the first 5 min of administration. The FNT metabolite was excreted at approximately the same rate from 0-30 and 30-60 min after FNT administration. The metabolite was not observed in media from FNT perfused kidneys or plasma from animals administered FNT. Analysis of purified metabolite by liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) determined the structure to be 5-nitro-2-furonitrile. This structure assignment was verified by chemical synthesis. Results demonstrate target organ metabolism of carcinogen.
Ballal
S
S
Geriatric Research, Education and Clinical Center (GRECC), Veterans Administration Medical Center, St Louis, MO 63125.
Mattammal
M B
MB
Lakshmi
V M
VM
Spry
L A
LA
Zenser
T V
TV
Davis
B B
BB
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D007668:Kidney / Q000378:metabolism*; D009581:Nitrofurans / Q000378:metabolism* / Q000652:urine; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013057:Spectrum Analysis; D015262:Xenobiotics / Q000378:metabolism
D009581:Nitrofurans; D015262:Xenobiotics; C001252:nefurthiazole