• Preventive Nutrition and Food Science
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• v.16 no.1
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• pp.1-7
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• 2011

The purpose of this study was to investigate the effect of enzyme-treated radish (Raphanus sativus L.) leaves on lipid metabolism in rats fed a high fat diet. Rats were divided into four experimental groups which were composed of a high fat diet group (HF group), a high fat diet with 10% radish leaf powder-supplemented group (MA group), a high fat diet with 5% enzyme-treated radish leaf powder-supplemented group (MB group) and a high fat diet with 10% enzyme-treated radish leaf powder-supplemented group (MC group). Total dietary fiber content of enzyme-treated radish leaves were greater than untreated radish leaves. Body weight gain and food efficiency ratio (FER) of the HF group increased compared to the MA, MB and MC groups. The serum total cholesterol, LDL-cholesterol and atherogenic index contents in the radish leaf powder-supplemented groups were lower than that of the HF group, while those values for the MB and MC groups were significantly lower than that of the HF group. The serum HDL-cholesterol contents of the MB and MC groups increased compared to the HF group. The hepatic triglyceride contents of the MA, MB and MC groups decreased compared to the HF group. In fact, the hepatic triglyceride contents of the MB and MC groups were significantly lower than the MA group. The hepatic total cholesterol contents of the MB and MC groups significantly decreased compared to those of the HF group. The fecal total cholesterol contents of the MA, MB and MC groups significantly increased compared to those of the HF group. These results indicate that supplementation with enzyme-treated radish leaves increase the useful fiber contents. Furthermore, it may have a pronounced impact on lipid metabolism of serum and liver in rats fed a high fat diet.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.361-369
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• 2020

Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.71-71
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• 1993

Carboxylesterase is widely distributed in the tissues of vertebrates, insects, plants and mycobacteria. Among various tissues of animals and humans, the highest esterase activity with various substrates is found in the liver. Kidney has moderate carboxylesterase activity in the proximal tubules. Considerable esterase activity is also found in the small intestine epithet elial cells and serum of mammals. Besides these tissues, carboxylesterase has been found in the lung, testis, adipose tissue, nasal mucosa and even in the central nervous system. Hepatic microsomal carboxylesterase catalyzes the hydrolysis of a wide variety of endogenous and exogenous compounds such as carboxylester, thioester and aromatic amide. Since carboxylesterases are important for metabolic activation of prodrugs and detoxification of xenobiotics, differences in substrate specificity and immunological properties of this enzyme are important in connection with choosing a suitable laboratory animal for the evaluation of biotransformation and toxicity of drugs. On the other hand, liver, kidney, intestine and serum were found to contain multiple forms of carboxylesterases in animal species and humans. In fact, we have purified more than fifteen isoforms of carboxylesterases from microsomes of liver, kidney and intestinal mucosa of nine animal species and humans. and characteristics of these isoforms were compared each other in terms of their physical and immunochemical properties. On the other hand, we have reported that hepatic microsomal carboxylesterases are induced by many exogenous compounds such as phenobarbital, polycyclic aromatic hydrocarbons, Aroclor 1254, aminopyrine and clofibrate. Later, we showed that some isoforms of hepatic carboxylesterase were induced by glucocorticoids such as dexamethasone and 16 ${\alpha}$-carbonitrile, but other isoforms were rather inhibited by these compounds. These findings indicate that involvement of carboxylesterases in the metabolism and toxicity of drugs should be explained by the isoforms involved. Since 1991, we have carried out detailed research investigating the types of carboxylesterases involved in the metabolic activation of CPT-11, a derivative of camptothecin, to the active metabolite, SN-38. The results obtained strongly suggest that some isoforms of carboxylesterase of liver microsomes and intestinal mucosal membrane are exclusively involved in CPT-11 metabolism. In this symposium, the properties of carboxylesterase isoforms purified from liver, kidney and intestine of animal species and humans are outlined. In addition, metabolism of CPT-11, a novel antitumor agent, by carboxylesterases in relation to the effectiveness will also be discussed.

• Korean Journal of Acupuncture
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• v.24 no.1
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• pp.113-129
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• 2007

Objectives : This research was performed to investigate the effect of acupuncture using invasive low level laser therapy (LLLT) at Yolgyol (LU7) + Yogu (LR5) on weight gain, food intake, food efficiency, lipid metabolism, atherogenic index, HTR (HDL-cholesterol to total cholesterol ratio) and morphological change of hepatic tissue in hyperlipdemia rats. Methods : Experimental groups were divided into high fat diet group (Control group), high fat diet and acupuncture therapy group at LU7 + LR5 (AT group), high fat diet and acupuncture group using 10 mW LLLT at LU7 +LR5 (LA10 group), high fat diet and acupuncture group using 20 mW LLLT at LU7+LR5(LA20 group), high fat diet and acupuncture group using 60 mW LLLT at LU7 + LR5 (LA60 group), once per 3 days during 9 weeks. Results : Body weight was decreased significantly in AT and LA20 groups compared with Control group. Food intake was increased significantly in LA60 group compared with Control group. Food efficiency was decreased significantly in LA10, LA20 and LA60 groups compared with control group. In the lipid metabolism, total cholesterol was decreased significantly in AT, LA10, LA20 and LA60 groups, triglyceride was decreased significantly in LA10, LA20 and LA60 groups, TG/HDL-cholesterol ratio was decreased significantly in LA 60 group compared with control group. In the morphological change, hepatic tissue were not showed balloning degeneration and irregular arrangement of hepatic cell in LA10 and LA20 groups with control group. Conclusions : Acupuncture using LLLT at LU7+LR5 can manage hyperlipemia by controlling body weight, food intake, food efficiency ratio and lipid metabolism.

• Nutrition Research and Practice
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• v.7 no.4
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• pp.287-293
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• 2013

This study determined the effects of fucoxanthin on gene expressions related to lipid metabolism in rats with a high-fat diet. Rats were fed with normal fat diet (NF, 7% fat) group, high fat diet group (HF, 20% fat), and high fat with 0.2% fucoxanthin diet group (HF+Fxn) for 4 weeks. Body weight changes and lipid profiles in plasma, liver, and feces were determined. The mRNA expressions of transcriptional factors such as sterol regulatory element binding protein (SREBP)-1c, Carnitine palmitoyltransferase-1 (CPT1), Cholesterol $7{\alpha}$-hydroxylase1 (CYP7A1) as well as mRNA expression of several lipogenic enzymes were determined. Fucoxanthin supplements significantly increased plasma high density lipoprotein (HDL) concentration (P < 0.05). The hepatic total lipids, total cholesterols, and triglycerides were significantly decreased while the fecal excretions of total lipids, cholesterol, and triglycerides were significantly increased in HF+Fxn group (P < 0.05). The mRNA expression of hepatic Acetyl-CoA carboxylase (ACC), Fatty acid synthase (FAS), and Glucose-6-phosphate dehydrogenase (G6PDH) as well as SREBP-1C were significantly lower in HF+Fxn group compared to the HF group (P < 0.05). The hepatic mRNA expression of Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and Acyl-CoA cholesterol acyltransferase (ACAT) were significantly low while lecithin-cholesterol acyltransferase (LCAT) was significantly high in the HF+Fxn group (P < 0.05). There was significant increase in mRNA expression of CPT1 and CYP7A1 in the HF+Fxn group, compared to the HF group (P < 0.05). In conclusion, consumption of fucoxanthin is thought to be effective in improving lipid and cholesterol metabolism in rats with a high fat diet.

• Biomedical Science Letters
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• v.24 no.4
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• pp.411-417
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• 2018

The aim of this study was to investigate the impact of participation in the 622 km hyper-ultra-marathon on hepatic metabolism and renal function in middle-aged men. Healthy middle-aged male amateur ultra-marathoners between the ages of 40 and 60. Blood was collected at the pre-race, immediately after 300 km, 622 km hyper-ultra marathon race, 72 hours (3 day) and 144 hours (6 day) after the race, AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), ${\gamma}$-GTP (gamma glutamyl transferase), T-Bil (total bilirubin), D-Bil (direct bilirubin), T-protein (total protein), albumin, uric acid, BUN (blood urea nitrogen), creatinne were analyzed. ALP was significantly increased at 300 km, 622 km, day 3 and day 6 than the pre-race. ${\gamma}$-GTP, T-protein, albumin, uric acid, BUN and creatinine were not significantly different between the distances and the recovery period respectively. AST and ALT were significantly increased at 300 km, 622 km, day 3 and day 6 than the pre-race, respectively (P<0.05) at day 3 and day 6 they showed significant decrease from 300 km and 622 km, respectively (P<0.05). T-Bil and D-Bil increased significantly at 300 km and 622 km, respectively (P<.05) and significantly decreased at day 3 (P<0.05) compared to the pre-race, at day 3 and day 6 they were decreased significantly than 300 km and 622 km, respectively (P<0.05). In conclusion, no disturbance of renal function was observed according to the distances and between the recovery period of 622 km hyper-ultra marathon race, but reversible hepatocyte function could be degraded and some hemolysis of blood vessels was induced.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1196-1202
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• 2005

Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces, the clearance of coad-ministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance ($CL_{t}$) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

• Korean Journal of Food Science and Technology
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• v.54 no.4
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• pp.398-402
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• 2022

Black chokeberry (Aronia melanocarpa), a rich source of polyphenols, exerts hypocholesterolemic effects. However, little is known about its effects on the regulation of the hepatic cholesterol metabolism and the underlying mechanisms. In the present study, the effects of polyphenol-rich black chokeberry extract (CBE) on hepatic cholesterol metabolism were investigated by measuring the expression of genes involved in the absorption, de novo synthesis, and efflux of cholesterol in HepG2 cells. There was a significant reduction in the expression levels of genes involved in cholesterol metabolism, the low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and sterol regulatory element-binding protein 2, in CBE-treated HepG2 cells. Meanwhile, CBE increased the expression levels of genes involved in cholesterol and bile acid efflux. The expression levels of mitochondrial fatty acid oxidation genes increased, whereas those of lipogenic genes decreased following CBE treatment. These data suggest that the consumption of black chokeberry may be beneficial for the prevention of hypercholesterolemia.

• Animal Bioscience
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• v.36 no.11
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• pp.1632-1646
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• 2023

Objective: The objective of the present study was to investigate the effect of dietary betaine (BT) supplementation on the hepatic transcriptome profiles in broiler chickens raised under heat stress (HS) conditions. Methods: A total of 180 (21-d-old) Ross 308 male broiler chicks were allotted to 1 of 3 treatment groups with 6 replicated cages in a completely randomized design. One group was kept under thermoneutral conditions at all times and was fed a basal diet (PC). Other 2 groups were exposed to a cyclic heat stress condition. One of the 2 groups under heat stress conditions was fed the basal diet as a negative control (NC), whereas the other group was fed the basal diet supplemented with 0.2% BT. All chickens were provided with diets and water ad libitum for 21 d. Following the experiment, the liver samples were collected for RNA sequencing analysis. Results: Broiler chickens in NC and BT group had decreased (p<0.05) growth performance. In the transcriptome analysis, the number of differentially expressed genes were identified in the liver by HS conditions and dietary BT supplementation. In the comparison between NC and PC treatments, genes related to energy and nucleic acid metabolism, amino acid metabolism, and immune system were altered by HS, which support the reason why heat-stressed poultry had decreased growth performance. In the comparison between NC and BT treatments, genes related to lipid metabolism, carbohydrate metabolism, and immune system were differently expressed under HS conditions. Conclusion: HS negatively impacts various physiological processes, including DNA replication, metabolism of amino acids, lipids, and carbohydrates, and cell cycle progression in broiler chickens. Dietary BT supplementation, however, offers potential counteractive effects by modulating liver function, facilitating gluconeogenesis, and enhancing immune systems. These findings provide a basis for understanding molecular responses by HS and the possible benefits of dietary BT supplementation in broiler chickens exposed to HS.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.59-66
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• 1997

This study was done to determine that vitamins I and C are synergistic in protecting liver cells during hepatic ischemia and repefusion. Rats treated with vitamins I and C were subjected to 60 min of hepatic ischemia and to 1 and 5 hr of reperfusion thereafter. Serum aminotransferase level and microsomal lipid peroxidation were markedly increased by ischemia/reperfusion. These increases were significantly attenuated by vitamins E, C or its combination. Hepatic wet weight-to-dry weight ratio was increased in ischemic group, but this increase was prevented by combination of vitamin I and C. Bile flow and cholate output were markedly decreased by ischemia/reperfusion and vitamin C alone and combination of vitamin I and C restored their secretion. Cytochrome P-450 content and aminopyrine N-demethylase activity were decreased by ischemia/ reperfusion and restored by vitamin C and combination of vitamin I and C to the level of sham-operated rat. Aniline p-hydroxylase activity was increased by ischemia/reperfusion and this increase was prevented by vitamin E. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory and microsomal functions by increasing lipid peroxidation and vitamins I and C synergistically ameliorates these changes.