Lipid peroxidation in mice fed a choline-deficient diet as evaluated by total hydroxyoctadecadienoic acid.
OBJECTIVE
The relevance of oxidative stress in mice fed a choline-deficient diet (CDD) was investigated in relation to the oxidative stress marker, hydroxyoctadecadienoic acid (HODE) in comparison with F2-isoprostanes. Further, the protective effects of antioxidants against oxidative damage were assessed by using HODE.


METHODS
We recently proposed total HODE as a biomarker for oxidative stress in vivo. Biological samples such as plasma, urine, and tissues were first reduced and then saponified to convert various oxidation products of linoleates to HODE. In the present study, this method was applied to measure oxidative damage in mice induced by CDD for 1 mo.


RESULTS
CDD, when compared with choline-controlled diet (CCD), increased liver weight and fatty acid accumulation but the increase in body weight was less significant. Remarkable increases in HODE and 8-iso-prostaglandin F(2alpha) in liver and plasma were observed when mice were fed with the CDD for 1 mo compared with the CCD. The HODE level was about two to three orders higher than the F2-isoprostane level. This increase was decreased to the level of the CCD when alpha-tocopherol or 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, a potent synthetic antioxidant, was mixed with the CDD. The stereoisomer ratio of HODE (9-and-13 (Z,E)-HODE/9-and-13 (E,E)-HODE) was decreased by CDD compared with CCD, which was spared by the addition of alpha-tocopherol and 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran. However, the increase in plasma glutamic-pyruvic transaminase and fatty acids in liver induced by the CDD was not recovered by any antioxidant.


CONCLUSIONS
This study clearly demonstrated that oxidative stress was involved in fatty liver formation induced by the CDD and that HODE was a good biomarker for an oxidative stress in vivo.
Yoshida
Yasukazu
Y
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Osaka, Japan. yoshida-ya@aist.go.jp
Itoh
Nanako
N
Hayakawa
Mieko
M
Habuchi
Yoko
Y
Inoue
Ruriko
R
Chen
Zhi-Hua
ZH
Cao
Jiaofei
J
Cynshi
Osamu
O
Niki
Etsuo
E
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism; D001572:Benzofurans; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000378:metabolism; D002794:Choline / Q000008:administration & dosage / Q000378:metabolism; D002796:Choline Deficiency / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D005234:Fatty Liver / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000975:Antioxidants; D001572:Benzofurans; D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; C495366:hydroxyoctadecadienoic acid; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D002794:Choline