Changes in the antioxidant system by TNP-470 in an in vivo model of hepatocarcinoma.
The objective of this study was to determine in a rat model of hepatocarcinoma (HCC) the effects of the antiangiogenic agent TNP-470 on antioxidant enzymes, including catalase (CAT), superoxide dismutases (Mn-SOD and Cu,Zn-SOD), and glutathione peroxidase (GPx). Tumor was induced in male Wistar rats by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, 2 times per week from weeks 20 to 28. Carcinomatous tissue was growing outside dysplastic nodules in rats with HCC. HCC caused oxidative stress demonstrated by increased lipid peroxidation and oxidized/reduced glutathione ratio that was accompanied by a reduced activity of antioxidant enzymes Cu,Zn-SOD, GPx, and CAT. In contrast, Mn-SOD activity and expression were higher in hepatocarcinoma than in control groups. These effects were absent in animals receiving TNP-470. No significant differences between untreated and TNP-470-treated rats were observed in the expression of the Cu,Zn-SOD, glutathione peroxidise, and CAT. We conclude that TNP-470 inhibits expression and activity of Mn-SOD induced by experimental hepatocarcinogenesis. Oxidative stress reduction by TNP-470 accounts for yet another anti-cancer effect of this molecule.
Mauriz
José Luis
JL
Department of Biomedical Sciences and Institute of Biomedicine, University of León, Ciberehd, and Hospital of León, León, Spain.
Durán
M Cristina
MC
Molpeceres
Virginia
V
Barrio
Juan Pablo
JP
Martín-Renedo
Javier
J
Culebras
Jesús M
JM
González-Gallego
Javier
J
González
Paquita
P
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002273:Carcinogens; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D003510:Cyclohexanes / Q000494:pharmacology*; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D002273:Carcinogens; D003510:Cyclohexanes; D016166:Free Radical Scavengers; D012717:Sesquiterpenes; D004052:Diethylnitrosamine; D000077609:O-(Chloroacetylcarbamoyl)fumagillol