Disease relevance of CCRIS 134

• BR-931, a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis [1].
• The hepatomegaly and peroxisome proliferation induced by BR-931 were comparable in degree to those resulting from feeding of an equivalent dose of Wy-14,643 [2].

High impact information on CCRIS 134

• As previously observed with BR 931, a hypolipidemic peroxisome proliferator, stimulation of liver cell growth by CsA did not entail changes in the production of HGF, TGF alpha or TGF beta 1 [3].
• Previous studies have demonstrated that BR-931, a hepatic peroxisome proliferator, can induce liver tumours in mice and rats [4].
• CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal [1].
• In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure [1].
• In further studies with clofibrate and a range of other known peroxisome proliferators (nafenopin, tiadenol, BR-931, Wy-14,643, and acetylsalicylic acid), induction of CAT and palmitoyl-CoA oxidation was observed with no increase in activity of another peroxisomal enzyme, D-amino acid oxidase [5].

Chemical compound and disease context of CCRIS 134

• BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits [1].

Biological context of CCRIS 134

• The potent peroxisome proliferator hepatocarcinogens WY-14,643, BR-931, and nafenopin, as well as mono(ethylhexyl)phthalate (MEHP), the principle metabolite of the weaker hepatocarcinogen di(2-ethylhexyl)phthalate) (DEHP), were evaluated in the in vitro rat hepatocyte DNA repair assay by quantitative autoradiography [6].

Associations of CCRIS 134 with other chemical compounds

• The mRNAs of the three peroxisomal beta-oxidation genes are induced over 20-fold in the livers of rats treated with nafenopin, Wy-14643, BR-931, and other structurally diverse peroxisome proliferators [7].
• These results failed to confirm the previously reported induction of UDS by WY-14,643 and BR-931 as determined by nuclear liquid scintillation counting [6].

References