Clofibrate oxidase

Van Den Munckhof RJM, Bosch KS, Frederiks WM. 1998. The different effects of the peroxisome proliferators clofibric acid and bis(2-ethylhexyl)phthalate on the activities of peroxisomal oxidases in rat liver. Histochem J 30 339-349. 

Clofibrate at a concentration of 0.5 mmol in culture medium maintained the cytochrome P-450 content of rat hepatocytes for up to 96 h. This effect was associated with a marked induction of lauric acid hydroxylation whereas little effect was observed on the metabolism of three other cytochrome p450 dependent mixed function oxidase substrates. 

Several pharmacogenomic studies, mainly in animal models, have characterized the molecular mechanisms contributing to the lipidlowering effect of fibrates. Hepatic transcription profiling of clofibrate or gemfibrozil-treated WT rats demonstrated increased expression of many genes involved in beta-oxidation, as well as FFA and cholesterol synthesis, including fatty acyl-Coenzyme A oxidase [45, 191, 192], acetyl-Coenzyme A acetyltransferase... 

In vitro and in vivo data on Cynomolgus monkeys (Table 17.3) and other species of monkeys (i.e., marmoset and Rhesus) indicate that the key events in the PPARa activator MOA are relatively nonresponsive in monkeys. Palmitoyl-CoA oxidase activity was evaluated in monkeys after in vivo exposure to a variety of PPARa activators [e.g., bezafibrate, clofibrate, DEHP, mono-2-ethylhexyl phthalate (MEHP), fenofibrate, nafenopin, and LY171883], and changes were minimal or nonexistent relative to controls (Klaunig et al. 2003). Moreover, Cynomolgus monkeys exposed to DEHP, DINP, or clofibrate failed to exhibit an increase in cell proliferation (Doull et al. 1999 Pugh et al. 2000). Cynomolgus monkeys treated for two weeks with clinically relevant doses of the PPARa activators fenofibrate or ciproflbrate exhibited increases in the number of hepatic peroxisomes (Hoivik et al. 

Wanders, R.J.A., Denis, S., Jakobs, C. ten Brink, H.J. (1992) Biochim. Biophys. Acta. 1124, 199-202. Identification of pristanoyl-CoA oxidase as a distinct, clofibrate non-inducible enzyme in rat liver peroxisomes. 

In 1976 Lazarow and deDuve [5] showed that peroxisomes contain a second p-oxidation system for fatty acids, and they showed that this system is induced in the hver of rats fed the hypohpemic drug clofibrate. The fatty acid oxidase of the peroxisomes has hydrogen peroxide as reaction product. The observations of Lazarow and deDuve led us to test whether the peroxisomes are active in the oxidation of the very long-chain fatty acids and whether the adaptation to their presence in the diet was caused by changed peroxisomal activity. 

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