PMID- 10083729
OWN - NLM
STAT- MEDLINE
DCOM- 19990407
LR  - 20171116
IS  - 1434-5161 (Print)
IS  - 1434-5161 (Linking)
VI  - 44
IP  - 2
DP  - 1999
TI  - A novel therapeutic trial of homogentisic aciduria in a murine model of
      alkaptonuria.
PG  - 79-84
AB  - Alkaptonuria is a rare autosomal recessive disorder characterized by homogentisic
      aciduria, ochronosis, and arthritis. Although a deficiency of homogentisic acid
      1,2-dioxygenase has recently been confirmed at the molecular level, no effective 
      treatment regimen has yet been developed for this disorder. In the present study,
      2(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a potent
      inhibitor of p-hydroxyphenylpyruvate dioxygenase (which catalyzes the formation
      of homogentisic acid from p-hydroxyphenylpyruvic acid) was adopted as a possible 
      therapeutic agent for alkaptonuria. NTBC dose-dependently reduced the urinary
      output of homogentisic acid in a murine model of alkaptonuria that had been
      created with ethylnitrosourea. These findings suggest that NTBC may be the first 
      potent pharmacotherapeutic agent for alkaptonuria.
FAU - Suzuki, Y
AU  - Suzuki Y
AD  - Department of Clinical Genetics, Kyushu University, Beppu, Japan.
      dsuzuki@kich.itami.hyogo.jp
FAU - Oda, K
AU  - Oda K
FAU - Yoshikawa, Y
AU  - Yoshikawa Y
FAU - Maeda, Y
AU  - Maeda Y
FAU - Suzuki, T
AU  - Suzuki T
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 0 (Cyclohexanones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitrobenzoates)
RN  - EC 1.13.11.27 (4-Hydroxyphenylpyruvate Dioxygenase)
RN  - K5BN214699 (nitisinone)
RN  - NP8UE6VF08 (Homogentisic Acid)
SB  - IM
MH  - 4-Hydroxyphenylpyruvate Dioxygenase/antagonists & inhibitors
MH  - Alkaptonuria/blood/*drug therapy/pathology
MH  - Animals
MH  - Cyclohexanones/pharmacokinetics/*therapeutic use
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacokinetics/*therapeutic use
MH  - Homogentisic Acid/*urine
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Nitrobenzoates/pharmacokinetics/*therapeutic use
EDAT- 1999/03/20 00:00
MHDA- 1999/03/20 00:01
CRDT- 1999/03/20 00:00
PHST- 1999/03/20 00:00 [pubmed]
PHST- 1999/03/20 00:01 [medline]
PHST- 1999/03/20 00:00 [entrez]
AID - 10.1007/s100380050114 [doi]
PST - ppublish
SO  - J Hum Genet. 1999;44(2):79-84. doi: 10.1007/s100380050114.