Microsomal and cytosolic epoxide hydrolases, the peroxisomal fatty acid β‐oxidation system and catalase

Abstract

A number of structurally unrelated hypolipidaemic agents and certain phthalate-ester plasticizers induce hepatomegaly and proliferation of peroxisomes in rodent liver, but there is relatively limited data regarding the specific effects of these drugs on liver non-parenchymal cells. In the present study, liver parenchymal, Kupffer and endothelial cells from untreated and fenofibrate-fed rats were isolated and the activities of two enzymes associated with peroxisomes (catalase and the peroxisomal fatty acid P-oxidation system) as well as cytosolic and microsomal epoxide hydrolase were measured.Microsomal epoxide hydrolase, cytosolic epoxide hydrolase and catalase activities were 7 -12-fold higher in parenchymal cells than in Kupffer or endothelial cells from untreated rats; the peroxisomal fatty acid f3-oxidation activity was only detected in parenchymal cells. Fenofibrate increased catalase, cytosolic epoxide hydrolase and peroxisomal fatty acid P-oxidation activities in parenchymal cells by about 1.5, 3.5-and 20-fold, respectively. The induction of catalase (2 -3-fold) and cytosolic epoxide hydrolase (3 -5-fold) was also observed in Kupffer and endothelial cells ; furthermore, a low peroxisomal fatty acid P-oxidation activity was detected in endothelial cells. Morphological examination by electron microscopy showed that peroxisomes were confined to liver parenchymal cells in untreated animals, but could also be observed in endothelial cells after administration of fenofibrate.Peroxisomes are ubiquitous cytoplasmic organelles present in plant and animal cells. They have both catabolic and anabolic functions [ 11 ; the former include respiration and the P-oxidation of fatty acids [2, 31. Respiration is catalyzed by oxidases which form H 2 0 2 and catalase which decomposes it. The peroxisomal P-oxidation reactions are the same as those of mitochondria1 f3-oxidatioq with the exception of the first reaction, in which electrons are transferred to oxygen by an oxidase in the peroxisomes, instead of to the electron transport chain, as in mitochondria.A small quantity of peroxisomes is observed in mammalian liver parenchymal cells [4]. After administration of several structurally unrelated hypolipidaemic drugs, or certain phthalate-ester plasticizers, a marked hepatomegaly and a large increase in both number and size of peroxisomes in liver parenchymal cells occurs [5]; furthermore, the activities of several enzymes in the liver (e.g. catalase, peroxisomal fatty acid P-oxidation system, epoxide hydrolase) are enhanced The mammalian liver is composed of several different cell types. Parenchymal cells constitute about 90% of the total cell mass, but only represent 65% of the total cell number [8]; the remainder corresponds to non-parenchymal cells, mainly Kupffer and endothelial cells. There is limited data regarding the specific effects of peroxisome proliferators on liver non-

Comparative anti-inflammatory effects of plant- and marine-derived omega-3 fatty acids explored in an endothelial cell line

“…This is consistent with observations in many other cell types and in humans in vivo [18]. Synthesis of DHA from DPA requires peroxosomal -oxidation and there is a report that ECs from rats do not express peroxisomal fatty acid -oxidation activity [45]. Future work should address this pathway in more detail in human ECs.…”

Occupational exposure to vinyl chloride and risk of hepatocellular carcinoma

“…Metabolic activities of enzymes involved in the detoxification pathways of VC-reactive metabolites, such as epoxide hydrolase and glutathione S-transferases, are localized mainly in parenchymal rather than non-parenchymal liver cells [19,20]. Indeed, notwithstanding the presumably much higher amounts of CEO in hepatocytes, where it is formed, than in non-parenchymal cells, similar N 2 ,3-ethenoguanine concentrations have been observed in these different liver cell types [9], consistent with preferential metabolic inactivation of CEO in hepatocytes.…”

The distribution, induction and isoenzyme profile of glutathione S-transferase and glutathione peroxidase in isolated rat liver parenchymal, Kupffer and endothelial cells

“…They constitute about 30 % of all liver cells, but they occupy only about 6 of total liver volume (Fabrikant, 1968;Greengard et al, 1972 Blouin et al, 1977;Blomhoff et al, 1984). In previous studies (Steinberg et al, 1987(Steinberg et al, , 1988 it was shown that oxidative and post-oxidative drug-metabolizing enzymes are not restricted to parenchymal cells in rat liver: in Kupffer and endothelial cells the activities of oxidative enzymes (e.g. aminopyrine N-demethylase, ethoxyresorufin O-de-ethylase) are very low, whereas the postoxidative enzyme activities (glutathione S-transferase, epoxide hydrolase) are relatively high.…”