Effects of acetylsalicylic acid on parameters related to peroxisome proliferation in mouse liver.
Male C57 BL/6 mice were exposed to 1.0% (w/w) acetylsalicylic acid (ASA) in their diet for 10 days and effects related to peroxisome proliferation were subsequently examined. A 2.2-fold increase in mitochondrial protein content was obtained. The activities of the peroxisomal enzymes, lauroyl-CoA oxidase, palmitoyl-CoA oxidation and catalase, were enhanced 4.5-, 4.0- and 2.1-fold, respectively. There was a dramatic increase (9.1-fold) in microsomal cytochrome P450 IVA-catalysed activity, a 1.6-fold induction of total microsomal P450 content and a 2-fold induction of microsomal cytochrome P450 reductase activity (measured as NADPH-cytochrome c reductase). Catalase activity in the cytosol was induced 5.2-fold and DT-diaphorase activity was increased 3.5- and 3.2-fold in the cytosol and mitochondria, respectively. There was a significant increase in the susceptibility of microsomes to lipid peroxidation. Smaller increases in superoxide dismutase, glutathione transferase and glutathione peroxidase activities were also observed. The possible relevance of these effects to the pharmacology of ASA is discussed.
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Y
Y
Cai
A K
AK
Sohlenius
K
K
Andersson
C
C
Sundberg
J W
JW
DePierre
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology; D011506:Proteins / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects*; D013347:Subcellular Fractions / Q000737:chemistry / Q000201:enzymology; D014157:Transcription Factors / Q000187:drug effects*
D011506:Proteins; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D001241:Aspirin