Distribution and peroxidative oxidation of 2-t-butyl-4-methoxyphenol in rat tissues after a single intraperitoneal dose.
The distribution of 2-t-butyl-4-methoxyphenol (BHA) and its conversion to 2,2'-dihydroxy-3,3'-di-t-butyl-5,5'-dimethoxydiphenyl (di-BHA) in rat tissues at different times (1-96 hr) following the intraperitoneal administration of a single dose of BHA (32 mg kg-1 body weight) were monitored by gas chromatography-mass spectrometry (GC/MS) analysis of both compounds. High BHA levels were found in the intestine and liver persisting up to 24 hours (5.5-20.7 and 1.8-3.3 micrograms g-1 wet weight, respectively). In these tissues, values of the area under the experimental concentration curve (AUC0-24) were 285 and 49 times higher, respectively, than those observed in plasma (945 ng mL-1 hr), AUC0-24 values in kidney, spleen, erythrocytes, and brain were 2-7 times higher, whereas values below those found in plasma were observed in lung and muscle. The metabolite di-BHA could be detected in the intestine, kidney, and spleen, amounting to 5-8% of BHA. These findings indicate that rat intestine is capable of transforming in vivo BHA into di-BHA even when the former compound is administered intraperitoneally and that this capacity is shared by the kidney and spleen.
Della Corte
L
L
Dipartmento di Farmacologia Preclinica, Università di Firenze, Italy.
Bianchi
L
L
Valoti
M
M
Sgaragli
G
G
D000818:Animals; D001711:Biotransformation; D002083:Butylated Hydroxyanisole / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D008401:Gas Chromatography-Mass Spectrometry; D007274:Injections, Intraperitoneal; D008297:Male; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D010545:Peroxides; D002083:Butylated Hydroxyanisole