Increase in peripheral oxidative stress during hypercholesterolemia is not reflected in the central nervous system: evidence from two mouse models.
In recent years oxidative stress has been widely implicated as a pathogenetic mechanism of several diseases, and a variety of indices and assays have been developed to assess this phenomenon in complex biological systems. Most of these biomarkers can be measured virtually in every biological fluid and tissue, providing us with the opportunity to assess their formation at local site of oxidative injury. However, despite their widespread use, it is still not completely clear how their peripheral formation correlates with the levels measured in the central nervous system. For this reason, we utilized two well-characterized animal models of chronic peripheral oxidative stress, low-density lipoprotein receptor (LDLR)-deficient and C57BL/6 mice on a high fat diet. After 8 weeks on the diet, we assessed isoprostane, marker of lipid peroxidation, and carbonyls, marker of protein oxidation, in several organs of these animals. Compared with animals on chow, mice on the high fat diet showed a significant increase in both biomarkers in plasma, heart, aorta and liver but not in brain tissues. This observation was confirmed by the selective accumulation of radioactivity in the peripheral organs but not in the brains of mice injected with tritiated isoprostane. Our findings indicate that in hypercholesterolemia the peripheral formation of oxidative products does not contribute to their levels found in the central nervous system.
Ding
Tao
T
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Room 124, John Morgan Building, Philadelphia, PA 19104, USA.
Yao
Yeumang
Y
Praticò
Domenico
D
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002490:Central Nervous System / Q000378:metabolism* / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects / Q000378:metabolism; D004195:Disease Models, Animal; D005526:Food, Formulated / Q000009:adverse effects; D006937:Hypercholesterolemia / Q000097:blood* / Q000503:physiopathology; D028421:Isoprostanes / Q000097:blood; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics*; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D004041:Dietary Fats; D028421:Isoprostanes; D011506:Proteins; D011973:Receptors, LDL; D002784:Cholesterol