• Biomedical Science Letters
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• v.11 no.4
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• pp.509-515
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• 2005

This study was conducted to determine the kinetics of cyclohexane metabolites (the biomarker on cyclohexane exposure), the changes of hepatic cyclohexane metabolizing enzyme activities and the metabolites of cyclohexane in urine or serum. The rats were sacrificed at 2, 4, 8, 12 and 24 hr after administration of one dose of cyclohexane (1.56 g/kg body weight, i.p.). The metabolites of cyclohexane in urine were identified as cyclohexanol, cyclohexanone, trans-l,2-cyclohexanediol and 1,4-cyclohexanediol with cyclohexane metabolite being 124.00, 0.78, 23.28 and 2.75 (g/g of creatinine, $1\times10^{-3}$). Most of the cyclohexanol and trans-l,2-cyclohexanediol were determined to be in the form of $\beta-glucuronide$ conjugates, whereas cyclohexanone and 1 ,4-cyclohexanediol were found as free forms. In toxicokinetics of serum cyclohexane metabolites, cyclohexanol showed a rapid increase, reaching the plateau at 4 hr, after this time rapidly decreased throughout 24 hr. Changes of cyclohexanone also showed the similar pattern with cyclohexanol except somewhat lower concentration. Trans-l,2-cyclohexanediol, however, showed a gradual increase until 12 hr with the continued same levels throughout 24 hr. On the other hand, 1,4-cyclohexanediol was detected as trace levels at 4 and 12 hr, respectively. The administration of cyclohexane led to a significant increase of hepatic aniline hydroxylase activity from 2 to 8 hr. The activity of hepatic alcohol dehydrogenase showed a significant increase at 4 hr and then were recovered to the level of the control at 24 hr. On the other hand, there were no differences in liver weightlbody weight between the control and cyclohexane-treated animals. However, there were the changes of aniline hydroxylase and alcohol dehydrogenase activities on time-dependent pattern after cyclohexane treatment, which influence on the degree of cyclohexane metabolites both in blood and urine. These results suggest that differential determination of cyclohexane metabolites in urine and serum may be able to be as a biomarker of cyclohexane-exposure in the body. But in this fields further study is needed.

• Nutrition Research and Practice
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• v.13 no.4
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• pp.286-294
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• 2019

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

• Journal of Nutrition and Health
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• v.55 no.2
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• pp.227-239
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• 2022

Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.3
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• pp.248-255
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• 2017

Increased hepatic enzymes are associated with insulin resistance, metabolic complications, and type 2 diabetes mellitus. Metabolically healthy obese (MHO) phenotype is not accompanied by metabolic complications and maintains insulin sensitivity, despite excessive body fat. The purpose of this study was to evaluate the clinical implications of hepatic enzymes in MHO men. The diagnostic criteria for MHO were based on NCEP-ATP III and obesity in adults was defined using WHO Asian-Pacific criteria. We used the data from 9,683 obese men aged between 20 and 70 years. The subjects were divided into three groups according to the diagnostic criteria: The metabolically healthy non-obese (MHNO, N=2,878), metabolically healthy obese (MHO, N=5,427), and metabolically abnormal obese (MAO, N=1,378). Obesity criteria were classified according to the standards set forth by WHO Asia-Pacific Criteria. AST, ALT, and GGT were significantly lower in the MHO group than in the MAO group (p<0.001, respectively). However, the hepatic enzyme levels were higher in the MHO group than in the MHNO group (p<0.001). Liver enzymes were associated with metabolic syndrome risk factors. Waist circumference, fasting glucose, total cholesterol, triglyceride, and HDL-C were risk factors for metabolic syndrome affecting liver enzymes. In conclusion, hepatic enzymes were found to predict metabolic abnormalities in metabolically healthy obese men.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.5
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• pp.900-907
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• 2000

The antioxidant effects of dichloromethane, ethylacetate or water fraction of kimchi added to the 1% cholesterol diet were studied. Six New Zealand white rabbits in each group were fed either control diet (basal diet containing 1% cholesterol) or experimental diet containing dichloromethane (CH$_2$Cl$_2$), ethylacetate (EtOAc) or water ($H_2O$) fraction of kimchi in the control diet for 16 weeks. The amount of each solvent fraction of kimchi added to the experimental diet was equivalent to 5% of freeze-dried kimchi. Levels of hepatic lipid oxidation expressed as TBARS or peroxide value for the experimental groups were lower than that of control (p<0.05). Liver homogenated of the experimental group containing dichloromethane fraction of kimchi inhibited LDL oxidation in the presence of Cu++ by 46% (p<0.05). The activities of catalase, Glutathione peroxidase (GSH-Px), Cu, Zn-superoxide (Cu, Zn-SOD) and Mn-superoxide (Mn-SOD) of experimental groups were lower than those of control group. Low enzyme activities observed from the kimchi solvent fraction groups might be due to the level of lipid oxidation progressed less in these groups. The most significant antioxidant effects were observed from dichloromethane fraction of kimchi among the experimental groups. The major fatty acids of hepatic phospholipid of rabbit were C18:2 and C18:0. But the major fatty acid profile was changed into C16:0, C18:0, C18:1, and C18:2 when rabbit was fed 1% cholesterol diet for 16 weeks, and this profile was almost the same as in rabbit fed diet containing kimchi solvent fraction. The ratio for unsaturated fatty acid to saturated fatty acid decreased by cholesterol induced diet and it was not corrected by kimchi solvent fractions.

• Animal Bioscience
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• v.34 no.3_spc
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• pp.405-416
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• 2021

Objective: This study evaluated the effects of feeding diets naturally contaminated with deoxynivalenol (supplemental 2 mg/kg) on health, growth, and the effects of a mycotoxin-detoxifying additive in newly-weaned pigs. Methods: Thirty-six pigs (27 day-old) were housed individually and assigned to 3 treatments for 5 weeks: CON (diet containing minimal deoxynivalenol), MT (diet with supplemental 1.9 mg/kg of deoxynivalenol), and MT+D (MT + mycotoxin-detoxifying additive, 0.2%, MegaFix, ICC, São Paulo, Brazil). The mycotoxin-detoxifying additive included bentonite, algae, enzymes, and yeast. Blood was taken at week 2 and 5. Jejunal tissue were taken at week 5. Data were analyzed using the MIXED procedure of SAS. Results: Pigs fed MT+D tended to have decreased (p = 0.056) averaged daily feed intake during week 1 than MT. At week 2, serum aspartate aminotransferase/alanine aminotransferase in MT tended to be lower (p = 0.059) than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating hepatic damages in MT and recovery in MT+D. Pigs fed MT had lower (p<0.05) blood urea nitrogen/creatinine than CON, supporting hepatic damage. At week 5, pigs fed MT tended to have reduced (p = 0.079) glucose than CON, whereas it was increased (p<0.05) for MT+D than MT, indicating impaired intestinal glucose absorption in MT, which was improved in MT+D. Pigs fed CON tended to have increased (p = 0.057) total glutathione in jejunum than MT, indicating oxidative stress in MT. Pigs fed MT+D had a reduced (p<0.05) proportion of Ki-67-positive cells in jejunum than MT, indicating lower enterocyte proliferation in MT+D. Conclusion: Feeding supplemental 1.9 mg/kg of deoxynivalenol reduced growth and debilitated hepatic health of pigs, as seen in leakage of hepatic enzymes, impaired nitrogen metabolism, and increase in oxidative stress. The mycotoxin-detoxifying enhanced hepatic health and glucose levels, and attenuated gut damage in pigs fed deoxynivalenol contaminated diets.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.9
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• pp.1274-1281
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• 2011

Dietary protein restriction affects lipid metabolism in rats. This study was performed to determine the effect of a low protein diet on hepatic lipid metabolism and insulin sensitivity in growing male rats. Growing rats were fed either a control 20% protein diet or an 8% low protein diet. Feeding a low protein diet for four weeks from 8 weeks of age induced a fatty liver. Expression of acetyl-CoA carboxylase, a key lipogenic enzyme, was increased in rats fed a low protein diet. Feeding a low protein diet decreased very low density lipoprotein (VLDL) secretion without statistical significance. Feeding a low protein diet down-regulated protein expression of microsomal triglyceride transfer protein, an important enzyme of VLDL secretion. Feeding a low protein diet increased serum adiponectin levels. We performed glucose tolerance test (GTT) and insulin tolerance test (ITT). Both GTT and ITT were increased in protein-restricted growing rats. Our results demonstrate that dietary protein restriction increases insulin sensitivity and that this could be due to low-protein diet-mediated metabolic adaptation. In addition, increased adiponectin levels may influences insulin sensitivity. In conclusion, dietary protein restriction induces a fatty liver. Both increased lipogenesis and decreased VLDL secretion has contributed to this metabolic changes. In addition, insulin resistance was not associated with fatty liver induced by protein restriction.

• Culinary science and hospitality research
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• v.17 no.1
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• pp.238-247
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• 2011

The aim of this study was designed to evaluate the effects of natural functional mixture(FM) on plasma BUN and lipid levels, hepatic lipid levels, hepatic antioxidant enzyme activities and plama aminotransferase activity in streptozotocin (STZ) induced diabe1ic rats. Total cholesterol (TC) level in the diabe1ic rats supplemented with FM(70.69 mg/dL) was reduced comparing to groups without FM(87.12 mg/dL). This results caused the increase of the ratio of HDL-cholesterol to TC (42.60 to 51.49 %). However, superoxide dismutase (SOD), cytosol catalase (CAT), glutathione peroxidase (GSH-Px), GSH and lipoperoxide (LPO) activities were not significantly changed, which indicated the supplementation with FM could not reduce the oxidative stress in diabetic rats. In addition, asperate aminotransferase (AST) activity in FM-diabetic rat was lower than that in diabetic group. This results showed supplementation with FM in rats could improve the hepatic function damaged by STZ-induced diabetes.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.8
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• pp.1310-1317
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• 2003

Effects of dietary cholesterol and/or taurine supplementation on plasma and hepatic lipid peroxidation status and antioxidant enzyme activities were evaluated in rats fed one of the following semisynthetic diets for 5 weeks: control diet (CD, cholesterol-free and taurine-free diet); high cholesterol diet (HCD, CD+1.5% cholesterol): high taurine diet (HTD, CD+1.5% taurine): high cholesterol and high taurine diet (HCHTD, HCD + 1.5% taurine). Plasma malondialdehyde (MDA) level was not influenced by dietary cholesterol or taurine supplementation, while hepatic MDA level was 70% higher in rats fed HCD compared to the value for CD rats (p<0.05). Our observation that taurine supplementation significantly decreased the hepatic MDA level of rats fed HCD, but failed to decrease lipid peroxidation of rats fed CD indicates that the protective effect of taurine in the liver against lipid peroxidation is manifested only under the hypercholesterolemic environment. Plasma and hepatic glutathione peroxidase (GSH-Px) activities were not affected by dietary supplementation of cholesterol or taurine. However, hepatic superoxide dismutase (SOD) activity was significantly reduced by dietary taurine supplementation (p <0.05), and thus significantly lower in rats fed HTD compared to the value for CD (p<0.05). Plasma total cholesterol concentration was positively correlated with hepatic cholesterol concentration as expected (r=0.712, p<0.001). Plasma (r=0.399, p<0.05) and hepatic cholesterol levels (r=0.429, p<0.05) showed a significantly positive correlation with hepatic MDA concentration, respectively. Plasma taurine concentration was negatively correlated with hepatic SOD activity (r=-0.481, p<0.01), and tended to be negatively correlated with hepatic GSH-Px activity without showing statistical significance (r=-0.188, p<0.05). These results indicate an antioxidative effect of taurine in rats with elevated level of lipid Peroxidation due to high intake of dietary cholesterol. Future application of taurine as a safe candidate for a hypolipidemic agent without adversely affecting body's antioxidant defense system is speculated.

• Journal of the Korean Society of Food Science and Nutrition
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• v.20 no.6
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• pp.527-537
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• 1991

To evaluate an effect of liver xanthine oxidase on the induction of liver damage, carbon tetrachloride (CCl4) was intraperitoneally injected twice at 0.1ml/100g body weight to the rate fed a low (LP)or high protein diet(HP) while the control group fed LP or HP received only olive oil. The changing rate of liver xanthine oxidas activity was compared with that of a free radical generating enzyme, liver aniline hydroxylase and a scavenging enzyme, glutathions S-transferase activity between the rate fed a LP and those fed HP, and the two groups treated with CCl4. Concomitantly, the degree of liver damage which could be considered as the paramete for CCl4 metabolism in case of CCl4-intoxicated animal was observed in the present experimental conditions and the effect of allopurinol, xanthine oxidase inhibitor, on the CCl4-toxicity of rate liver was alos demostrated. On the other hand, the comparative effect of actinomycin D on the liver and serum xanthine oxidase of CCl4-treated rats fed HP with that of those fed LP and the kinetics of purifed liver enzyme from the liver of CCl4-treated rats fed HP was also compared with that of those fed LP to clarify the differences of xanthine oxidase activity between two groups. The increasing rate of liver weigth/body wt, serum levels of ALT and the decreasing rate of hepatic ALT activity and protein contents to each control group were higher in CCl4-treated rats fed HP than those fed LP. Under the animal models as indentified by the present data herein, the liver xanthine oxidase activity was higher in CCl4-treated rats fed HP than those fed LP, and the control group fed HP also showed the much higher activity xanthine oxidase than that fed LP, whereas there were no differences in the activity of hepatic aniline hydroxylase and glutathions S-transferase between the two group treated with CCl4. Although the hepatic aniline hydroxylase activity was somewhat higher in the rats fed HP than those fed LP, the increasing rate of liver xanthine oxidase to the rats fed LP was higher in those fed HP than that of liver aniline hydroxylase. The degree of liver damage identified such as liver weight and serum ALT activity was less in the CCl4-treated rats pretreated with allopurinol. These results suggest that even a system at which xanthine oxidase acts as well as the drug metabolizing enzyme may influence the acelatin of CCl4 metabolism. In addition, the purified liver xanthine oxidase from CCl4-treated rats fed HP showed decreased Km value when compared to its control group. The Km value of liver xanthine oxidase of CCl4-treated rats fed LP showed a similar Km value with its control group. Furthermore, the decreasing rate of liver and serum xanthine oxidase acitivity in CCl4-treated rats pretreated with actinomycin D to the CCl4-treated rats was higher in rats fed HP than in those fed LP. These results suggest that the inductino of xanthine oxidase in CCl4-treated rats fed HP may be greater than in those fed LP.