• 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.

• Preventive Nutrition and Food Science
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• v.12 no.4
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• pp.202-208
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• 2007

Persimmon is well-known as a Korean traditional medicine for alleviating coughs and enhancing blood circulation; it is also used for treatment of hypertension, cancer, diabetes and atherosclerosis. To evaluate the protective properties of persimmon leaf methanol extract (PLME) and persimmon fruit methanol extract (PFME) administration on acute ethanol-induced hepatotoxicity, C57BL/6 male mice were gavaged with or without persimmon extracts for 1 week. Hepatotoxicity was then induced by gavage of 5 g/kg BW ethanol. After 12 hr of ethanol administration, blood and liver were collected and analyzed for biochemical markers of hepatotoxicity. The results showed PLME and PFME treatments decreased the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with ethanol control. Both PLME and PFME reduced serum lactate dehydrogenase (LDH) activity, but elevated alcohol dehydrogenase (ADH) activity. Serum triglyceride (TG) and hepatic cholesterol levels were significantly decreased when treated with PLME and PFME. Liver malondialdehyde (MDA) levels were significantly decreased in PLME and PFME groups compared with ethanol control. Furthermore, the administration of PLME and PFME significantly increased the activities of catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-red). In summary, PLME and PFME appeared to prevent hepatic injury by accelerating alcohol metabolism by increasing alcohol-metabolizing enzyme activities, by activating the antioxidative enzyme system against oxidative stress, and by decreasing fat accumulation, which is evidenced by decreased hepatotoxic indices in serum.

• Journal of Haehwa Medicine
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• v.8 no.1
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• pp.711-726
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• 1999

Aging in the life form occurs due to a gradual progression of the body growth and degeneration. Morphological and functional changes in the body decreases the adaptation and prevention capacity leading into the decline of a life force. Various studies have been released to examine the anti-aging effects of herbal prescriptions. This experiment has chosen Boganhwan which is used for the deficiency of the liver function and studied the anti-aging factors by examining the biotransformation enzymes. The following results were obtained in this study: 1. Hepatic lipid peroxide activity was significantly suppressed in the experimental group treated with Boganhwan for 2 weeks at the dosage of 350mg/kg, while other dosage groups did not present much changes. 2. Insignificant changes were shown for the cytochrome P-450 level, aminopyrine demethylase, and aniline hydroxylase (AH) activities. Cytochrome P-450 do not appears to be a part of the detoxification scheme. 3. Boganhwan decoction treated group showed most significant increase of superoxide dismutase (SOD), catalase, superoxide, and glutathione activities at the concentration of 350mg/kg and 500mg/kg. 4. Glutathione S-transferase and glutathione made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. 5. Hepatic glutathione concentration, protein bound-SH, and nonprotein bound-SH made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. From the above results, Boganhwan decoction played an important role in eliminating foreign substances in the body excluding cytochrome P-450 enzyme system. Thus, Boganhwan decoction can provide substantial aid in preventing and treating senile related illnesses.

• The Korean Journal of Zoology
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• v.38 no.4
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• pp.498-504
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• 1995

The effeds of riboflavin defidency on the biosynthesis of flavin pepddes and levels of flavoenzymes and catecholamines have been investigated. The percentage of 14C. riboflavin radioactivity formed in mitochondria appeared to increase up to 2 weeks but started to decline at 3 weeks. A significant increase of radioactivity incorporation into mitochondria and into trypsin-digestable plus trypsin-non-digestibie flavin peptides was detected in riboflavin-deficient animals. More than 35% of incorporation was observed at the end of the first week and 160% higher incorporation was observed in fiavin peptide after the second week. Activities of MAO and succinate dehydrogenase were affected markedly by riboflavin status whereas those of acetyichoilnesterase were not affected. Riboflavin defidency also brought about marked reductions in levels of epineplrrine and norepinephrine. it is concluded that the levels of flavin peptides, MAO and succinate dehydrogenase, and catecholamines were affected significanily by the availability of riboflavin and in particular the duration of its depiction.

• Nutrition Research and Practice
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• v.2 no.2
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• pp.80-84
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• 2008

Beneficial effects of dehydroepiandrosterone (DHEA) supplement on age-associated chronic diseases such as cancer, cardiovascular disease, insulin resistance and diabetes, have been reported. However, its mechanism of action in hepatocellular carcinoma in vivo has not been investigated in detail. We have previously shown that during hepatocellular carcinogenesis, DHEA treatment decreases formation of preneoplastic glutathione S-transferase placental form-positive foci in the liver and has antioxidant effects. Here we aimed to determine the mechanism of actions of DHEA, in comparison to vitamin E, in a chemically-induced hepatocellular carcinoma model in rats. Sprague-Dawley rats were administered with control diet without a carcinogen, diets with 1.5% vitamin E, 0.5% DHEA and both of the compounds with a carcinogen for 6 weeks. The doses were previously reported to have anti-cancer effects in animals without known toxicities. With DHEA treatment, cytosolic malate dehydrogenase activities were significantly increased by ${\sim}5$ fold and glucose 6-phosphate dehydrogenase activities were decreased by ${\sim}25%$ compared to carcinogen treated group. Activities of Se-glutathione peroxidase in the cytotol was decreased siguificantly with DHEA treatment, confirming its antioxidative effect. However, liver microsomal cytochrome P-450 content and NADPH-dependent cytochrome P-450 reductase activities were not altered with DHEA treatment. Vitamin E treatment decreased cytosolic Se-glutathione peroxidase activities in accordance with our previous reports. However, vitamin E did not alter glucose 6-phosphate dehydrogenase or malate dehydrogenase activities. Our results suggest that DHEA may have decreased tumor nodule formation and reduced lipid peroxidation as previously reported, possibly by increasing the production of NADPH, a reducing equivalent for NADPH-dependent antioxidant enzymes. DHEA treatment tended to reduce glucose 6-phosphate dehydrogenase activities, which may have resulted in limited supply for de novo synthesis of DNA via inhibiting the hexose monophophaste pathway. Although both DHEA and vitamin E effectively reduced preneoplastic foci in this model, they seemed to fimction in different mechanisms. In conclusion, DHEA may be used to reduce hepatocellular carcinoma growth by targeting NADPH synthesis, cell proliferation and anti-oxidant enzyme activities during tumor growth.

• Journal of Veterinary Clinics
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• v.38 no.4
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• pp.204-209
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• 2021

A seven-month-old castrated male Chihuahua weighing 1.6 kg presented with generalized tonic-clonic seizure following ingestion of isoniazid. Emergency treatment with three doses of diazepam (total 1.5 mg/kg, intravenous [IV]) and phenobarbital (15 mg/kg IV) was administered. The seizure stopped after administration of propofol (constant rate infusion [CRI]; 0.2 mg/kg/min). Blood analyses showed mildly increased serum blood glucose concentration, hyperkalemia, and hyperphosphatemia. On suspicion of isoniazid toxicity, activated charcoal (1 g/kg, orally), lipid emulsion (CRI; 9 mL/hr), and pyridoxine hydrochloride (70 mg/kg IV) were added to the treatment regimen. Twelve hours after presentation, the dog showed increased serum liver enzyme activities, serum blood urea nitrogen, and creatinine concentrations indicating hepatic and renal failure. Twenty-two hours after presentation, blood analysis still revealed increased liver enzyme activities, blood urea nitrogen, and creatinine concentrations with low blood glucose concentration. Twenty-six hours after presentation, the dog's vital signs deteriorated and the owner elected for the dog to be euthanized. This is the first report of the clinical course of isoniazid toxicosis in a dog in South Korea. Furthermore, to our best knowledge, this is the first report where secondary multiple organ failure was observed due to isoniazid toxicosis. Clinicians should be aware of the possibility of isoniazid toxicosis in dogs. Rapid initiation of treatment after clinical recognition is warranted in such cases.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.1
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• pp.11-20
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• 2022

Objectives: The purpose of this study was to investigate the effects of Gabyeobda tea (GT) on anti-inflammation in ice induced high fat diet (HFD). Methods: The C57BL/6 mice fed HFD were administrated with GT once daily for 8 weeks. The changes of body weight, calorie intake levels were measured in mice. The level of serum total cholesterol, triglyceride, high density lipoprotein cholesterol, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were measured in mice by enzyme-based assay. It was also observed the histological changes of liver, and fat tissues with hematoxylin and eosin staining. Further real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay were employed to detect inflammatory cytokine levels such as tumor necrosis factor (TNF)-𝛼, interleukin (IL)-6, and IL-1𝛽. Results: HFD+GT group, which was administered with GT with HFD, showed no body weight gain compared with HFD group. However, levels of GOT, GPT, and inflammatory cytokines such as TNF-𝛼, IL-6, and IL-1𝛽 in the blood of HFD+GT group were significantly reduced compared with HFD group. In addition, the messenger RNA (mRNA) expression level of the IL-12 gene was significantly reduced and the mRNA expression level of the IL-10 was increased in the liver. Conclusions: It suggests that Gabyeobda tea can alleviate inflammatory responses induced by high fat diet by inhibiting inflammatory cytokines production.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.846-855
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• 2008

Objects : The aim of this study was to investigate the influence of five herbal medicines on cytochrome P450 3A4 drug-metabolizing enzymes in human liver microsomes. Methods : To use human liver microsomes, an extract of five herbal medicines, which are Artemisia princeps Pampan, Sophora jeponica Linne, Panax notoginseng F. H. Chen, Lithospermum Erythrorhizon Sieb., and Cirsium maackii Maxim, which together are called Jihyulyak(止血藥, drugs for arresting bleeding, hemostatics), was co-incubated and measured for relative enzyme activity in incubation condition compared to ketoconazole, a representative inhibitor of CYP 3A4. Results : We showed that all five of the traditional herbal medicines had no inhibition effect of CYP 3A4 at 10, 20, 30, 40, and $50{\mu}g/ml$ doses in human liver microsomes, although Sophora japonica Linne(SJL) showed a little inhibition at about 81% inhibition rate of control. However, this result is not enough to prove that SJL has a CYP 3A4 inhibition effect. Moreover, we can't make sure that those rates had significant induction effect on CYP 3A4. Conclusions : The result of this study could support that those herbal medicines are safer than chemical drugs, even if this is the basic step to prove that result.

• Parasites, Hosts and Diseases
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• v.33 no.4
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• pp.395-398
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• 1995

A 56 year-old Korean housewife/farmerlgoat keeper suffered from right upper quadrant pain and fever with chills. In the abdominal sonogram and computerized tomography, multiple, 2-3 cm, irregular shaped cavities were observed in the right lobe of liver. A liver biopsy revealed extensive central necrosis with Characot-Leyden crystals surrounded by palisading histiocytes, eosinophil-rich inflammatory infiltration. Worm was not observed. However, the serologic test for Fusciola-specific IgG antibody by micro-ELISA was positive. Prior antibody levels did not differ and eosionophilia persisted 6 and 16 months after praziquantel treatment although the cavitaxy lesions in the liver disappeared 6 months after the treatment. Reported herein is a human case of invasive fascioliasis diagnosed clinically by a combination of radiological, histopathological and serological studies.

• Applied Microscopy
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• v.39 no.4
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• pp.283-289
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• 2009

In order to examine the effect of Injinhotang extract on the liver cancer induced by N-nitrosodiethylamine (NDEA) and carbon tetrachloride ($CCl_4$) in Rats. The animals were divided into three groups. The normal (Nor) group were fed basal diet. Control (Con) group were administered with NDEA (200 mg/kgb.w., i.p.) and $CCl_4$. Injinhotang extract (IJH) group treated with Injinhotang extract (260 mg/kg/day) for 8 weeks after NDEA+$CCl_4$. Enzymic antioxidants, such as superoxide dismutase (SOD) and catalase levels were determined in all the groups of animals. The activities of SOD were significantly increased in the Con, but the activities of catalase were decreased in the Con, but the anti-oxidative enzyme activities of superoxide dismutase and catalase were increased in the IJH. In the immunohistochemistry observation, treatment of Injinhotang extract reduced the rates of p53 immunoreactivity. According to the electron microscopical observation, in the liver cancer cells were increased the smooth endoplasmic reticulum and dilated the rough endoplasmic reticulum in the Con compared with IJH. These results suggest that administration of Injinhotang extract suppress or retard NDEA and $CCl_4$-induced liver cancer.