Lipid-metabolizing enzymes, CoASH and long-chain acyl-CoA in rat liver after treatment with tiadenol, nicotinic acid and niadenate

The tumour promoter 12-O-tetradecanoylphorbol-13-acetate increases the activities of some peroxisome-associated enzymes in in vitro cell culture

“…When the C18 cells were cultured in the presence of a non-toxic concentration of TPA (20 nM) for 9 days, the specific activity of the palmitoyl-CoA hydrolase activity (24.6 nmol min-' mg-' protein) was increased -2.5 fold compared to control cells (9.7 nmol min-mg-1 protein) (Figure 1). Tiadenol administration, a potent hypolipidemic drug (Berge & Bakke, 1981) also enhanced this enzyme activity in the C18 cells and MCA16 cells . When the C18 cells were cultured in the presence of 2OnM TPA for 24 h, the activity of the palmitoyl-CoA hydrolase activity declined -30% (Figure 2).…”

“…A marked stimulation of cyanide-insensitive palmitoyl-CoA oxidation, carnitine acetyltransferase and palmitoyl-CoA hydrolase activities with a moderate enhancement of the catalase activity, is characteristic of the preferential stimulation of peroxisomal enzymes associated with fatty acid metabolism produced in vivo by tiadenol, clofibrate, d(2-ethylhexyl)phthalate and other peroxisome proliferators (Berge & Bakke, 1981;Berge et al, 1984;Bakke & Berge, 1982;Moody & Reddy, 1978). Recently and partly in this study we have shown that addition of tiadenol to cultures of C18 and MCA16 cells enhanced the corresponding enzyme activities .…”

“…Peroxisome proliferating agents are also associated with an increase in the activities of some enzymes, i.e. cyanide-insensitive palmityol-CoA dehydrogenase (usually termed peroxisomal ,Boxidation), catalase, carnitine acetyltransferase and cytosolic palmitoyl-CoA hydrolase (Reddy et al, 1974;Moody & Reddy, 1978;Inestrosa et al, 1979;Berge et al, 1981;Berge & Bakke, 1981;Berge et al, 1983). Hypolipidemic drugs as well as phthalates have been found not to be genotoxic (Warren et al, 1980;Von Daniken et al, 1984).…”

Peroxisome proliferators show tumor‐promoting but no direct transforming activity in vitro

“…Reddy and collaborators (Reddy and Rao, 1978;Reddy and Quershi, 1979;Reddy et al, 1980;Reddy et al, 1976) showed that several structurally unrelated hypolipidemic drugs with peroxisome proliferative properties would produce tumors in the livers of rats and mice. Recently, we have shown that 2 other hypolipidemic drugs, tiadenol and niadenate, caused liver enlargement and an increase in the activity of some peroxisome-associated enzymes (Berge and Bakke, 1981;Bakke and Berge, 1982;Berge et al, 1984). These 2 hypolipidemic drugs, however, have not been tested for carcinogenic activity in rodents.…”

Tiadenol‐mediated induction of peroxisomal enzymes in cultured C3H/10T1/2CL8 cells and in chemically transformed C3H/10T1/2 MCA16 cells

“…Neither of the two cell lines contained any appreciable urate oxidase activity. The responses of these cells to hypolipidemic drugs show that they constitute a useful system for studies on the role of peroxisomes in lipid metabolism and the relationship between hypolipidemic activity and carcinogenic potential of these drugs.Hypolipidemic drugs such as clofibrate (ethyl-pchlorophenoxy-isobutyrate) , tiadenol (bis(hydroxy-ethy1thio)-1,lO-decane) and niadenate (a prodrug of tiadenol and nicotinic acid), which are quite dissimilar in chemical structure (Berge and Bakke, 1981;Bakke and Berge, 1982) cause liver enlargement and hepatic peroxisome proliferation in rats. These drugs markedly increase the activities of cyanide-insensitive palmitoyl-CoA oxidation, palmitoyl-CoA hydrolase and carnitine acetyl-transferase, but have comparatively little effect on the activities of catalase and urate oxidase (Lazarow, 1977;Moody and Reddy, 1978; Markwell et al, 1977;Berge and Bakke, 1981).…”