Exogenous Products Research Articles

Captopril Restores Endothelium-Dependent Relaxation Induced by Advanced Oxidation Protein Products in Rat Aorta

To explore whether advanced oxidation protein products (AOPP) can cause endothelial dysfunction in vitro, and whether captopril exerts beneficial effect on impaired endothelium-dependent relaxation induced by exogenous advanced oxidation protein products and to investigate the potential mechanisms. Both the Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside-induced endothelium-independent relaxation of aortic rings were measured by recording isometric tension after the rings were exposed to AOPP-BSA in the absence or presence of captopril to assess the injury effect of AOPP-BSA and the protective effect of captopril on the aortic endothelium, respectively. Co-incubation of aortic rings with AOPP-BSA (3 mmol/L) for 90 minutes resulted in a significant inhibition of EDR to ACh, but had no effects on endothelium-independent relaxation to SNP. After incubation of the rings in the co-presence of captopril (3 to 30 micromol/L) or enalaprilat (30 micromol/L) with AOPP-BSA (3 mmol/L) for 90 minutes, captopril significantly and enalaprilat only partly attenuated the inhibition of EDR induced by AOPP-BSA. This protective effect of captopril (30 micromol/L) was abolished by N-nitro-L-arginine methyl ester (10 micromol/L), an inhibitor of nitric oxide synthase. Furthermore, the superoxide anion scavenger superoxide dismutase (SOD, 200 U/mL), and the nitric oxide precursor L-arginine (3 mmol/L) also ameliorated the impaired EDR caused by AOPP-BSA. But D-arginine had no effect on the impaired EDR caused by AOPP-BSA. AOPP-BSA can trigger endothelial dysfunction and captopril can protect the endothelium against functional damage induced by AOPP-BSA in rat aorta, increase nitric oxide bioavailability. The mechanisms of endothelial dysfunction induced by AOPP-BSA may include the decrease of NO and the generation of oxygen-free radicals.

Toll-Like Receptors-Intrarenal Mechanisms beyond Immune Function: Renal-Associated TLR2 Mediates Ischemia/Reperfusion Injury in the Kidney.

Toll-Like Receptors-Intrarenal Mechanisms beyond Immune Function: Renal-Associated TLR2 Mediates Ischemia/Reperfusion Injury in the Kidney.

#22 Plasma cytokine levels in highly stressed children

A novel family of chemotactic cytokines or chemokines, essential for the directed migration of leukocytes to sites of inflammation, has been identified during the past decade. To obtain microgram amounts of natural chemokines, normal (e.g., freshly isolated leukocytes, connective tissue cell cultures) or malignant cell lines have to be selectively induced with endogenous (cytokines) or exogenous (bacterial, viral, or plant) products. We have developed a four-step procedure that allows for the complete purification of active C-C (MCP-1, MCP-2, MCP-3, RANTES, MIP-1α and MIP-1β) and C-X-C (IL-8, GRO-α, GRO-β, GRO-γ, GCP-2, ENA-78, IP-10, PF-4, and CTAPIII/βTG/NAP-2) chemokines from bulk volumes of culture supernatant. This method is applicable for the isolation of recombinant chemokines. Conditioned medium was first concentrated and partially purified on silicic acid or controlled pore glass beads. Further purification to homogeneity was achieved using heparin–Sepharose or antibody affinity chromatography, cation exchange FPLC, and reverse-phase HPLC. Purification of chemokines was monitored by testing column fractions for biological (chemotaxis) or immuno (RIA, ELISA) activity and protein content (SDS–PAGE). Homogeneous proteins were identified by amino-terminal or internal protein sequence analysis.

Excision of foreign gene product with cathepsin D in chicken hepatoma cell line

To easily and rapidly recover exogenous gene products from chicken egg yolk, we constructed pVTG-catD (VTG, vitellogenin; catD, cathepsin D), a vector cassette carrying two catD-recognition signal peptides (catD-RSPs) in addition to the cloning site. An enhanced green fluorescence protein (EGFP)-encoding DNA fragment was ligated into the pVTG-catD. When the resultant construct pVTG-EGFP-catD containing histidine- and myc-tags was transfected into the chicken hepatoma cell line LMH, EGFP-expression at 24 h post-cultivation was confirmed by fluorescence microscopy. Because a signal peptide (NTVLAEF) encoded in pVTG-EGFP-catD is recognized by catD, the VTG-EGFP fusion protein digested with catD was detectable by Western blotting. Digested exogenous gene product was recovered with nickel resin. These results indicate that catD-recognition sites bearing pVTG-catD and His-tags are functional in chicken LMH cells. Therefore, the system described here may be of use in making excision exogenous gene products in the chicken and in creating homozygous knock-in chickens.

Periorbital treatment, 2 major contributions: Botulinum toxin and volumetric fillers

Botulinum toxin, by creating a „biological section“, produces a very efficient, safe and durable treatment of the dynamic periorbital wrinkles. Indeed, those lines are usually treated with much more risks and less durability by procedures as face lifts and other surface medical treatments. In other hands, in this peiorbital area: If a loose of volume is existing, volumetric fillers, as fat grafting and other effective exogenous products, are the best approach.

ToF-SIMS analysis of elemental distributions in human hair

Elemental distributions on whole and longitudinal sections of hairs plucked from the scalp were studied with the surface sensitive technique time-of-flight secondary ion mass spectrometry (ToF-SIMS). Endogenous and environmental influences on the distributions of elemental species were identified. The cuticle scales appear to play the major role in the accumulation of exogenous products. The functionality of the outer surfaces and scale edges each preferentially bind different elemental species. The majority of elements considered accumulated longitudinally on the outer surface of the hair above the scalp level. Internally, most elemental signals (especially Al) decreased longitudinally once exposed to the environment with the exception of Si, which showed an increase. Images of elemental distributions within the medulla suggest that regions of different reactivity exist and show a variable ability to accumulate elemental species. The greatest signal intensities were observed in the cuticle and medulla regions rather than the cortex. The cuticle is continually exposed to environmental contamination and the medulla may, or may not, exist in a hair. Therefore, the components of a hair that potentially contribute the most to the elemental concentrations (i.e. the cuticle and medulla) are also the most variable, and as such greatly complicate the interpretation of elemental concentrations in hair. Results also suggest that bleaching hair can enhance the accumulation of contaminants.

Effects of in vitro hyperthermia on proliferative responses and lymphocyte activity.

Fever is induced by both exogenous products like endotoxin, and endogenous cytokines, most notably IL-1 and IL-6, and tumour necrosis factor (TNF). These mediators are believed to interact with the hypothalamus, to induce enhanced body temperature. However, little is known about the biological effects of fever on the function of the immune system. We here report that a 90-min pulse of mild hyperthermia (40 degrees C) induces enhanced proliferation of peripheral blood mononuclear cells (PBMC). This proliferative response was completely inhibited by antibodies to MHC class II, which had no effect on mitogen-induced proliferation of PBMC. The enzyme-linked immunospot (ELISPOT) assay is a sensitive method for detection of single cells secreting antibodies or cytokines. A 90-min pulse of mild hyperthermia (40 degrees C) induced a significantly enhanced immunoglobulin production in PBMC, as determined by ELISPOT, indicating B cell activation. The T cell cytokine pattern both with and without stimulation with hyperthermia differed between individuals. Enhanced interferon-gamma (IFN-gamma) secretion was noted at 39-41 degrees C. This IFN-gamma response was inhibited by antibodies to MHC class II and thus was MHC class II-restricted and dependent on antigen-presenting cells. None of the individuals tested showed IL-4 response after stimulation with hyperthermia. These findings favour the notion that fever may play an important role in immune responses, and it is possible that fever may act as a physiological adjuvant, with effects on the immune system both in infection and inflammation of other origins.

Roles of antimicrobial peptides such as defensins in innate and adaptive immunity

A number of antimicrobial peptides such as defensins have multiple functions in host defence. Defensins are produced not only by phagocytic cells and lymphocytes, but also by the epithelial cell...

Exogenous advanced glycosylation end products induce diabetes-like vascular dysfunction in normal rats: a factor in diabetic retinopathy.

Diabetic retinopathy has been shown to be directly associated with the degree and duration of hyperglycemia, and advanced glycosylation end products (AGEs) have been implicated in this pathological process. The purpose of the experiments reported here was to study the effect of AGE deposition on retinal vascular damage which leads to diabetic retinopathy. Intravenous injection of exogenous AGEs was used to treat wild-type non-diabetic Sprague-Dawley rats. One of the two retinal slides from each animal was treated using immunohistochemical staining to label retinal vascular AGE deposition, the other H&E staining for counting of capillary pericytes. The results were compared with the findings in untreated wild-type and diabetic controls and in rats treated with unmodified rat serum albumin (RSA). After 2 weeks of continuous treatment, AGEs were identified in the retinal vascular tissue of the AGE-RSA-injected group. The average number of retinal capillary pericytes per 10x100 microscope power field was 4.313+/-0.34 (mean +/- SD) in the AGE-RSA-injected group, compared with 5.798+/-0.481 in the control group ( P<0.01). These experiments demonstrate that AGEs, independent of other metabolic factors, can induce vascular change resembling that of diabetic retinopathy.

Damage to subcellular structures evoked by lipid peroxidation.

Subcellular Structures, Lipid Peroxidation, Free Radical Scavengers The influence of lipid peroxidation (LP) on the rate of disruption of rat liver and kidney subcellular structures was studied under two experimental conditions. Damage to cell organelles was found only when peroxidation process carried out into large granule fraction suspensions. Exogenous thiobarbituric acid positive products were noneffective as membrane labilizers. Age, organ and cell organelle-linked differences in the response towards LP produced damage were observed. Rat liver peroxisomes showed higher stability than those of kidney with respect to injury induced by peroxidation process. In addition, in rat kidney and neonatal rat liver samples the lysosomes were found to be more sensitive than mitochondria to the damaging effect of this process. Thiourea, an inhibitor of diene conjugate formation as well as manitol and ethanol known as hydroxyl radical scavengers were tested as terminators of LP and as membrane protectors. Effectiveness was demonstrated only for thiourea.

Arachidonic acid directly activates members of the mitogen-activated protein kinase superfamily in rabbit proximal tubule cells

To explore the roles of eicosanoids in arachidonic acid-induced mitogen-activated protein kinase (MAPK) signal transduction, we have shown that exposure of proximal tubular cells to arachidonic acid induces phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), two members of the MAPK superfamily. We observed that ketoconazole, an inhibitor of the cytochrome P450 pathway, blocked ERK but not JNK activation. Direct regulation of arachidonic acid on mitogen-activated protein kinase (MAPK) signaling pathways was evaluated more directly by utilizing specific enzyme inhibitors of the cytochrome P450 metabolic pathway and by comparing the relative efficacy of arachidonic acid versus its cytochrome P450 metabolites (exogenous and endogenous), eicosatetraynoic acid (ETYA), and other fatty acids on the phosphorylation of members of the MAPK superfamily (ERKs, JNK, and p38(MAPK)), by utilizing early passage rabbit proximal tubular epithelial cells. Arachidonic acid activated p38(MAPK), a third member of the MAPK superfamily, in a time- and concentration-dependent manner. Studies designed to evaluate the ability of arachidonic acid and its cytochrome P450 metabolites (endogenously and exogenously) to stimulate ERKs, JNK, and p38(MAPK) found four conclusions. First, the metabolites of arachidonic acid generated endogenously by cytochrome P450 2C1 significantly augmented basal ERK activity, whereas the metabolites generated by the 2C2 isozyme significantly augmented basal p38(MAPK) activity. However, their effects were less profound than arachidonic acid itself. In contrast, there were no significant effects with transfection of either isozyme on basal JNK activity. Second, a variety of exogenous cytochrome P450 products were less potent than arachidonic acid on a molar basis in stimulating the activity of all three MAPKs. Third, ketoconazole and 17-octadecynoic acid, inhibitors of the cytochrome P450 pathway, as well as PPOH and DDMS, inhibitors of the epoxygenase and omega-hydroxylase pathways, respectively, failed to significantly reduce the effects of arachidonic acid to activate ERK and p38(MAPK) (JNK was not evaluated). Finally, arachidonic acid, its inactive analog ETYA, and other fatty acids with differing chain lengths and degrees of saturation stimulated the activity of all three MAPKs. These observations substantiate a role for arachidonic acid and other fatty acids in signaling linked to the MAPK superfamily in rabbit proximal tubular epithelium without the necessity of conversion to cytochrome P450 metabolites.

In vivo maturation and migration of dendritic cells.

The hallmark of immunity is antigen (Ag) recognition. From early life until death we face countless Ags; many are deleterious and come from the outside world. However, lymphocytes, the mediators of specific acquired immunity, are usually not exposed where foreign antigens are encountered. Thus a system must ferry these Ags from the periphery into inner tissues where lymphocytes comfortably reside or traffic. Clearly, translocating Ags from the periphery to the lymphoid niches is a pivotal function whereby the dendritic cell (DC) system initiates immune responses. DCs, however, are not passive Ag couriers; a dynamic process not fully understood is triggered by Ag deposition. Strategically poised at the boundaries between the inner and the outside world, in a way bridging innate and acquired immunity, DCs sample, trap, engulf, and digest Ags of very diverse origin, in what is called Ag processing. Antigenic fragments are then regurgitated, exposed at the cell surface through one of three molecular pathways [Major histocompatibility complex (MHC) CI and CII, and CD1)] responsible for an efficacious Ag presentation. Concomitantly, DC bear an arsenal of powerful costimulatory molecules [CD40; CD80; CD86; DC-specific/intercellular adhesion molecule type 3-grabbing, non-integrin (DC-SIGN)] and the potential to produce critical cytokines [chemokines, interleukin-12 (IL-12), etc.], thus ensuring the initiation and the fate of acquired immunity. The DC system is particularly efficient, not just translocating, but also transforming antigens sampled at the earlier local milieu into an immunologically accesible language, becoming an excellent reporter of the previous antigenic past, translating the conundrum posed by viruses, bacteria, proteins, etc., into T-cell receptor (TCR) ligands; a short-peptide vocabulary that T cells especially now understand. A highly dynamic process is thus triggered by encountering Ags; while these are carried and processed to be appropriately presented, DCs in turn experience a variety of changes: migratory, phenotypical, functional; all encompassed in the term maturation. Essentially, DC maturation means to change from an antigen-capturing to an antigen-presenting, T-cell-priming mode, a process whereby DCs convert antigens into efficacious immunogens, express the necessary cytokines and costimulatory molecules, thus appropriately initiating the specific, acquired clonal immunity.

Direct gene transfer into rabbit peripheral nerve in vivo.

Exogenous gene suture was used to achieve peripheral nerve anastomoses to probe into the feasibility that the sites of anastomoses of nerves directly transfer gene and thus enable gene to be expressed at the sites of anastomoses under the condition that perfect nerve anastomoses are ensured. PCMV beta plasmid containing cytomegalovirus promoter (CMV promoter) and Escherichia coli (E. coli) beta-Galactosidase (beta-Gal) structural gene (lacZ gene) was conducted. A soaked medical 8-0nylon suture was used to perform epineurial repair of rabbit sciatic nerve. In the control group a suture soaked in sucrose PBS was used, while in the experimental group a suture soaked in PCMV beta plasmid solution was applied. The sites of anastomoses of nerves by stages were taken out, and beta-Gal histochemical staining was performed and beta-Gal enzyme activity was assayed with 5-bromo-4-chloro-3-indolyl-beta-D-galactoside. Results showed that the sites of anastomoses of nerves were taken out 2 days, 7 days, 14 days and 30 days respectively after the operation. The beta-Gal histochemical stains at the sites of anastomoses showed no indigo positive cells at different stages in the control group, whereas displayed indigo positive cells in the experimental group. In the control group, no beta-Gal enzyme activity was detected at different stages after operation, but in the experimental group, beta-Gal enzyme activity could be detected from the 3rd day to the 30th day after operation. It was concluded that by using exogenous gene suture, exogenous gene could be transferred to the sites of peripheral nerve and expressed the exogenous gene expression products with bioactivity, which provided the feasibility of using gene therapy to accelerate the recovery of nerve function.

Effect of food enzymes on AME and composition of digesta from broiler chickens fed on diets containing non-starch polysaccharides isolated from lupin kernel

1. The effects of lupin non-starch polysaccharides (NSPs) on apparent metabolisable energy (AME) and composition of digesta from broiler chickens were examined in a dose-response experiment in conjunction with a single combination of 2 commercial enzyme products known from previous studies to partially depolymerise NSPs in diets containing sorghum, casein and lupin kernel. The 7-d experiment was conducted on broiler chickens (24 to 31 d of age) in metabolism cages. 2. The basal diet used in this study contained (in g/kg) sorghum (low tannin) 800, casein 134, celite 20 and vitamins and minerals 46. The inclusion rate for each enzyme product was 0.2 g/kg. Lupin kernel isolate (containing 560 g/kg total NSPs) replaced some of the sorghum and casein. The dose rates of lupin kernel isolate (50, 100 and 150 g/kg) were equivalent to dietary inclusion rates of 80, 160 and 240 g/kg, approximately, of untreated lupin kernel from Lupinus angustifolius cultivar Gungurru. 3. Inclusion of lupin kernel isolate in the diet depressed AME and bird performance, and raised ileal viscosity and excreta moisture, in a dose-dependent manner. 4. A combination of 2 proprietary enzyme products improved dietary AME by 0.3 MJ/kg dry matter. Enzymes reduced excreta moisture when inclusion of lupin kernel isolate was 50 g/kg (equivalent to lupin kernel at 80 g/kg, approximately) but not at higher inclusions. 5. Food enzymes partially depolymerised some insoluble NSPs in lupin kernel isolate, which increased ileal viscosity and soluble NSP content of digesta. 6. It was concluded that development of appropriate exogenous enzyme products could lead to lupin NSPs being used as an energy source for poultry.

Molecular approach in cancer epidemiology: early detection of carcinogen-induced mutations in a whole genome (Review).

Chronic exposure of organisms to endo- or exogenous genotoxic products results in the accumulation of mutations in the genome and eventually to the development of cancers. Early detection of these mutations would allow the identification of at risk individuals who present a high load of mutations either because of an occupational or environmental exposure, or because of less efficient DNA repair processes. However, highly specific and sensitive assays are required to allow the detection of point mutations in a whole genome. We review a long-term study on the mutagenesis induced in E.coli by an aromatic amide, the N-2-acetylaminofluorene. A major contribution of this work was to reveal the presence of specific mutation hot spot sequences. Taking advantage of this observation, we designed a specific, sensitive and semi-quantitative in vitro assay allowing the detection of carcinogen induced mutations. This assay has been validated in vivo and demonstrate the sensitivity of the technique in early detection of mutations and its usefullness in molecular epidemiology, early diagnostic and prognosis.

Regulation of c-Myc through Phosphorylation at Ser-62 and Ser-71 by c-Jun N-Terminal Kinase

The expression of c-myc promotes cell proliferation and also sensitizes cells to various extracellular apoptotic stimuli. However, signal pathways regulating the function of Myc proteins during apoptosis are unknown. c-Jun N-terminal kinase (JNK) is activated by various apoptotic stimuli, but neither the target molecule(s) or the action of JNK has been identified in Myc-mediated apoptosis. Here, we found that JNK selectively interacted with, and phosphorylated, c-Myc at Ser-62 and Ser-71 as confirmed with phospho-c-Myc-specific antibodies. Interestingly, dominant negative mutant JNK(APF) impaired the c-Myc-dependent apoptosis, but not mutated c-Myc (S62A/S71A)-dependent apoptosis triggered by UV irradiation. Furthermore, c-Myc (S62A/S71A)-expressing NIH3T3 cells were not sensitized like wild type c-Myc-expressing NIH3T3 cells to JNK-activating apoptotic stimuli, such as UV and Taxol. These results indicate that the JNK pathway is selectively involved in the c-Myc-mediated apoptosis and that the apoptotic function of c-Myc is directly regulated by JNK pathway through phosphorylation at Ser-62 and Ser-71.

Cell surface aggregation of elastin receptor molecules caused by suramin amplified signals leading to proliferation of human glioma cells.

We have recently shown that glioma cell lines, as well as cells of human malignant gliomas in situ, synthesize tropoelastin. In addition, glioma cells degrade tropoelastin using metalloproteinase(s), and the resulting peptides, incapable of assembling in the extracellular fibers, interact with the 67-kDa cell surface elastin binding protein (EBP), to transduce signals leading to up-regulation of cell proliferation. In this report, we show that exposure to the polysulfonated bis-naphthylurea suramin causes accumulation of physiologically active EBP molecules on the cell surface of a panel of glioma cell lines (U87, MG, U251 MG, U343 MG-A, U373 MG, SF 126, SF188, SF539), which results in an increase of cellular attachment to elastin-coated dishes and in an efficient binding of radiolabeled tropoelastin. Moreover, 100-200 microM suramin stimulates [3H]-thymidine incorporation by those tropoelastin-producing glioma cell lines, but not by A 2058 melanoma cells, which do not produce elastin. Treatment of all glioma cell lines with 100 microM suramin consistently increased expression of cyclin A and its cyclin-dependent kinase, cdk 2, to levels reached following the exposure to exogenous elastin-degradation products (kappa-elastin). Our data suggest that a suramin-stimulated accumulation of EBP molecules on the cell surface of glioma cells amplifies the elastin-derived signals, leading to their progression through the cell cycle.

Antioxidant Response to Harmone‐Containing Product in Kentucky Bluegrass Subjected to Drought

The purpose of this study was to determine if exogenous hormonecontaining products (HCP) (seaweed extract and humic acid) enhance endogenous antioxidant concentration in Kentucky bluegrass (Poa pratensis L.) subjected to drought. Two‐week‐old seedlings of Kentucky bluegrass (cv. Plush) were treated with seaweed extract at 326 g ha−1, humic acid (25% active) at 5 L ha−1, alone or in combination, and grown under two soil moisture levels (−0.03 MPa and −0.5 MPa) for 5 wk, and subsequently analyzed for antioxidant concentration and growth. The HCP treatments improved leaf water status and enhanced shoot and root growth regardless of soil moisture levels. Water stress induced a significant increase of α‐tocopherol, ascorbic acid, and β‐carotene content but did not influence superoxide dismutase (SOD) activity. Foliar application of HCP significantly increased α‐tocopherol, ascorbic acid, β‐carotene content, and SOD activity, especially under low soil moisture (LSM). Positive correlations between antioxidants and antioxidants with growth parameters were observed in Kentucky bluegrass grown under either LSM or high soil moisture (HSM). These data indicate that HCP enhancement of the grass's endogenous antioxidant status may contribute to turfgrass drought tolerance.

Aggrecan and link protein affect cell adhesion to culture plates and to type II collagen.

Cartilage is a hypocellular tissue in which a balance of matrix molecules, especially aggrecan and link protein, play a critical role in maintaining structural integrity. To study the role of aggrecan and link protein in mediating cell activities, we have stably expressed them in NIH/3T3 fibroblasts and observed the effect on cell-substratum interactions. Overexpression of either protein destabilized the cell-substratum interaction. However, when both were co-expressed, the interaction between cell and substratum was less impaired. Similar results were obtained on type II collagen-coated plates. The addition of exogenous gene products into fibroblast cell lines and chondrocyte culture had the same effect as expression of the genes. The addition of exogenous hyaluronan to the growth medium or treatment of cells with hyaluronidase also decreased cell adhesion, indicating that hyaluronan also plays a role in the cell-substratum adhesion. The presence of aggrecan seems to increase the amount of link protein on the cell surface. Chondrocytes expressing high concentrations of aggrecan and link protein were maintained within a matrix network and were able to survive in suspended culture. Imbalances in aggrecan or link protein concentrations, or degradation of hyaluronan, disrupted the network and caused the chondrocytes to aggregate or adhere to the plates.

The effect of dietary vitamin E supply and a moderately oxidized oil on activities of hepatic lipogenic enzymes in rats.

Diets rich in polyunsaturated fatty acids (PUFA) are well known to suppress hepatic lipogenic enzymes compared to fat-free diets or diets rich in saturated fatty acids. However, the mechanism underlying suppression of lipogenic enzymes is not quite clear. The present study was undertaken to investigate whether lipid peroxidation products are involved in suppression of lipogenic enzymes. Therefore, an experiment with growing male rats assigned to six groups over a period of 40 d was carried out. Rats received semisynthetic diets containing 9.5% coconut oil and 0.5% fresh soybean oil (coconut oil diet, peroxide value 5.1 meq O2/kg oil), 10% fresh soybean oil (fresh soybean oil diet, peroxide value 9.5 meq O2/kg oil), or 10% thermally treated soybean oil (oxidized soybean oil diet, peroxide value 74 meq O2/kg oil). To modify the antioxidant state of the rats, we varied the vitamin E supply (11 and 511 mg alpha-tocopherol equivalents per kg of diet) according to a bi-factorial design. Food intake and body weight gain were not influenced by dietary fat and vitamin E supply. Activities of hepatic lipogenic enzymes were markedly influenced by the dietary fat. Feeding either fresh or oxidized soybean oil diets markedly reduced activities of fatty acid synthase, (FAS), acetyl CoA-carboxylase, (AcCX), glucose-6-phosphate dehydrogenase, (G6PDH), 6-phosphogluconate dehydrogenase, and ATP citrate lyase (ACL) relative to feeding the coconut oil diet. Moreover, feeding oxidized soybean oil slightly, but significantly, lowered activities of FAS, AcCX, and ACL compared to feeding fresh soybean oil. Activities of hepatic lipogenic enzymes were reflected by concentrations of triglycerides in liver and plasma. Rats fed the coconut oil diet had markedly higher triglyceride concentrations in liver and plasma than rats consuming fresh or oxidized soybean oil diets, and rats fed oxidized soybean oil had lower concentrations than rats fed fresh soybean oil. The vitamin E supply of the rats markedly influenced concentrations of thiobarbituric acid-reactive substances in liver, but it did not influence activities of hepatic lipogenic enzymes. Because the vitamin E supply had no effect, and ingestion of an oxidized oil had only a minor effect, on activities of hepatic lipogenic enzymes, it is strongly suggested that neither exogenous nor endogenous lipid peroxidation products play a significant role in the suppression of hepatic lipogenic enzymes by diets rich in PUFA. Therefore, we assumed that dietary PUFA themselves are involved in regulation of hepatic lipogenic enzymes. Nevertheless, the study shows that ingestion of oxidized oils, regardless of the vitamin E supply, also affects hepatic lipogenesis, and hence influences triglyceride levels in liver and plasma.