Prevention by acetylsalicylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, L-amino acid-defined diet in rats.
Effects of acetylsalicylic acid (ASA) (aspirin) on the pathogenesis of fatty liver, cirrhosis and hepatocarcinogenesis caused by a choline-deficient L-amino acid-defined (CDAA) diet were examined in male Fischer 344 rats fed a CDAA diet supplemented with 0, 0.1, 0.2, 0.4 or 0.8% ASA for 30 weeks. ASA at concentrations of > 0.2% prevented the development of both cirrhosis and preneoplastic and neoplastic nodules, but without any directly associated prevention of fatty changes. ASA also prevented hepatocyte proliferation and the generation of thiobarbituric acid-reactive substances and 8-hydroxydeoxyguanosine caused by feeding the CDAA diet, analyzed, respectively, after 1, 12 and 12 weeks. The results clearly indicate that the anti-inflammatory drug ASA, which is not a lipotropic factor, can prevent the pathogenesis of cirrhosis and hepatocarcinogenesis caused by a CDAA diet, which is possibly partly associated with the prevention of reactive oxygen species production.
Denda
A
A
Department of Oncological Pathology, Nara Medical University, Japan.
Tang
Q
Q
Endoh
T
T
Tsujiuchi
T
T
Horiguchi
K
K
Noguchi
O
O
Mizumoto
Y
Y
Nakae
D
D
Konishi
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000627:therapeutic use*; D002796:Choline Deficiency / Q000150:complications*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000517:prevention & control*; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000596:Amino Acids; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D016718:Arachidonic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D001241:Aspirin