• Molecules and Cells
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• 제41권5호
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• pp.401-412
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• 2018

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

• The Korean Journal of Physiology and Pharmacology
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• 제17권5호
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• pp.455-461
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• 2013

Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

• Korean Journal of Clinical Laboratory Science
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• 제38권3호
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• pp.196-202
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• 2006

Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However the most troublesome problem of lamivudine treatment is the emergence of lamivudine-resistant strains with amino acid substitution in the YMDD motif of DNA polymerase gene during the treatment. The aim of this study was to determine the mutation of YMDD motif (codon 552) and codon 528 in chronic HBV patients with lamivudine therapy using PCR-direct sequencing and to investigate the relationship between lamivudine mediated HBV mutation and HBeAg. HBV DNA was extracted from serum samples of HBV patients and amplified by nested PCR with two sets of primer pairs selected in HBV DNA polymerase gene. Amplified PCR product was analyzed by 2% agarose gel electrophoresis and direct sequencing. HBV mutation was detected in 124 out of 207 samples (60%). Single mutation was 50.8% for M552I, 43.5% for M552V, 5.7% for M552I/V and the L528M mutation was 67.0%. Double mutation was 43.6% for M552V/L528M, 33.1% for M552I/L528(wild type), 17.7% for M552I/L528M and 5.6% for M552I/V/L528M. Serine mutation at YMDD motif (M552S) was not found and the L528M mutation frequently accompanied M552V type. In this study, the typical difference of frequencies for HBV mutation depending on HBeAg was not found. Moreover, the PCR-direct sequencing method used in this study might be a powerful tool for the mutation study in clinical reference laboratories with high volume.

• Journal of Preventive Medicine and Public Health
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• 제24권2호
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• pp.195-210
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• 1991

Fatty liver is caused by derangement of fat metabolism and can be reversed by removal of contributing factors. The contributing factors of fatty liver is known to be overweight, chronic alcoholism, diabetes mellitus, malnutrition, and drug abuse such as tetracycline. This study was carried out on 1335 persons who visited 'Soon Chun Hyang Human Dock Center' from March to June 1990. In analysis of the data, prevalence of fatty liver diagnosed by ultrasonogram by age and sex, laboratory finding between fatty liver group and normal group, and odds ratio of known contributing factors, were compared. The results obtained are as following ; 1) The prevalence rate of fatty liver diagnosed by ultrasonogram is 29.6% in male and 11.5% in female. 2) Age groups with high prevalences are $40{\sim}50's$ in male (32.0%) and 50's in female (24.5%). 3) The fatty liver shows significant association with style (p<0.05), whereas not with hepatitis B-virus surface antigen (p>0.05). 4) All laboratory values except alkaline phosphatase and bilirubin are elevated significantly in accordance with the degree of fatty liver (p<0.01). 5) Fatty liver diagnosed by ultrasonogram showed so strong associations with body index, triglycerides and gamma-glutamyl transferase for males, and body index and fasting blood sugar for females that these factors may be used as supplementary data in establishing diagnosis of fatty liver. 6) Odds ratio of contributing factors are as follows ; If the odds ratio of below 29 year of age is 1.0 then that of $30{\sim}39$ is 1.74 (p=0.33), $40{\sim}49$ is 2.47 (p=0.10), $50{\sim}59$ is 2.86 (p=0.0570), over 60 is 1.81 (p=0.34). If the odds ratio of female is 1.0 then that of male is 5.67 (p<0.01). If the odds ratio of body index below zero is 1.0 then that of $0{\sim}9$ is 5.08 (p<0.01), $10{\sim}19$ is 12.37 (p<0.01), $20{\sim}29$ is 29.19 (p<0.01), 30 above is 154.02 (p<0.01). If the odds ratio of below 99 mg/dl FBS is 1.0 then that of $100{\sim}120$ is 106 (p=0.76), over 120 is 1.91 (p=0.02). If the odds ratio of below $29{\mu}/1{\gamma}-GT$ is 1.0 then that of $30{\sim}s59$ is 2.11 (p<0.01), $60{\sim}90$ is 1.87 (p<0.05), 90 above is 1.69 (p=0.15). If the odds ratio of below 149 mg/dl TG is 1.0 then $150{\sim}199$ is 1.49 (p=0.05), $200{\sim}250$ is 1.09 (P=0.77), 250 above is 2.53 (p<0.01). In summary, early diagnosis of fatty liver could be made by ultrasonogram supplemented with body index and nm triglyceride. The fatty liver could be preventive by avoiding contributing factors such as obesity, alcohol intake, high blood sugar appropriately.