• The Journal of Internal Korean Medicine
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• v.44 no.4
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• pp.751-756
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• 2023

Objective: This study attempts to increase awareness of hepatotoxicity caused by antipsychotic drugs and to provide updated information on drug-induced liver injury (DILI) to physicians in Korean medicine (KM) clinics. Methods: This study presents a detailed case of a female patient diagnosed with DILI attributed to antipsychotic drugs, highlighting the improvement observed through laboratory findings. Results: A 56-year-old female patient with underlying disorders, including mixed connective tissue disease and depression, was under medical care. One day, she reported experiencing intense fatigue and distressing sensations, prompting the author to order blood tests. The levels of AST and ALT were significantly elevated by more than 2.5-fold, indicating hepatocellular DILI. The RUCAM score for antipsychotic drugs was 9, as no other medications, including herbal medicine, were being taken. Upon discontinuation of the antipsychotic drugs, the patient's laboratory findings returned to normal levels within 2 weeks, accompanied by a recovery of subjective symptoms. Conclusion: This study presents a noteworthy case of hepatotoxicity caused by antipsychotic drugs, serving as an illustrative example that highlights the crucial need for awareness among doctors of KM in clinical settings.

• The Journal of Korean Medicine
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• v.33 no.3
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• pp.95-104
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• 2012

Objectives: There are some controversies over the safety of herbal medication in relation to liver function. This report, therefore, aimed to analyze the safety issue of herbal medications by scrutinizing the liver function tests (LFT) results of 82 psoriasis patients on herbal medications for 3 months at an oriental medical clinic. Methods: We tested psoriasis patients' liver function periodically with Reflotron Plus of Roche during the herbal medication. Then we statistically analyzed the LFT results to see if there was any negative change. Results: Statistical analysis on the LFT results of 82 psoriasis patients showed no meaningful change caused by herbal medication over 3 months. Conclusions: From this result we conclude that herbal medication for 3 months does no harm to patients' liver function.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.05a
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• pp.1-4
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• 1998

Impaired insulin action in Type 2 diabetes is thought to lead to hyperglycemia, with both environmental and complex genetic factors playing key roles. Although the primary lesion in Type 2 diabetes is unknown, a number of studies suggest that metabolic defects in the liver, skeletal muscle and fat, and pancreatic ${\beta}$-cells contribute to the disease. These metabolic abnormalities are characterized by the overproduction of hepatic glucose, impaired insulin secretion, and peripheral insulin resistance. In current pharmacological treatment of Type 2 diabetes, sulfonylurea (SU) drugs have mainly been used as oral hypoglycemic drugs to stimulate endogenous insulin secretion from ${\beta}$ cells. SU drugs, however, sometimes aggravate the disease by causing fatigue of the pancreatic ${\beta}$ cells, which leads to reduced drug efficacy after long-term treatment. This class of drugs also leads to enhanced obesity arising from the stimulation of endogenous insulin secretion in obese Type 2 diabetic patients, plus an increased incidence of SU-induced hypoglycemia. Since 1980, a major challenge has been made by us to develop a potential pharmacological therapy for the treatment of insulin resistance in peripheral tissues and/or suppression of abnormal hepatic glucose production in Type 2 diabetic patients. Such a drug would be expected to have fewer side effects and retain long-term efficacy.

• The Korea Journal of Herbology
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• v.28 no.6
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• pp.39-45
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• 2013

Objectives : This study was conduct to compare of histological changes on four target organs which related with diabetes in streptozotocin-induced diabetic rats. Methods : Diabetes was induced in male Sprague-Dawley rats by consecutive injection of streptozotocin (STZ) at different doses of 30, 40 and 50 mg/kg for 5 days. After 4 weeks, all rats were sacrificed, five different organs such as pancreas, liver, kidney, and lung were isolated and observed their histological changes by hematoxylin and eosin (H&E), Periodic acid-Schiff (PAS) and Masson's trichrome staining. The changes of body weight, blood glucose, and food and water intake were also measured. Results : The multiple administration of STZ was induced diabetes in rats with hyperglycemia, decrease of body weight, increase water and food intake, and histopathological changes of target organs, compared with those of normal rats in both dose-dependent and time-dependent manner. In histological analysis, pancreas was showed decrease of the islet numbers with beta-cell loss. Kidney showed morphological damage with glomerulus hypertrophy, and also lung was showed bronchial epithelial damage with inflammatory cells infiltration. In liver, the portal vein and hepatic artery could not observed, and showed inflammatory cell infiltration with liver fibrosis. Conclusions : These results suggest that the increase of the capacity of STZ, each of the more chronic disease, it can be seen that the damage was deep. Thus, evaluate the resulting drug appropriate depending on the purpose of the model is expected to be selected.

• The Journal of Internal Korean Medicine
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• v.22 no.2
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• pp.251-256
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• 2001

In western medicine, there are some reports about herbal medicine induced hepatitis, but in oriental medicine, there are few reports about that. We experienced one case of drug acute cholestatic-hepatitis in the treatment of oriental medicine for HNP. We treated the patient with acupuncture, physical therapy and herb medicine. The patient's symptoms improved after two weeks of treatment. In the course of treatment, the patient intermittently complained of general weakness, nausea, yellowish urin, dyspepsia, and abdominal discomfort. We recognized that total bilirubin(7.2mg/dl), direct bilirubin(5.5mg/dl), serum transaminase(AST 360U/L, ALT 354U/L), alkaline phosphatase(16.6 K/A), urobilinogen(++) and bilirubin(++) were elevated. We diagnosed drug induced hepatitis. We stopped giving herb medicine and began giving Saeng gan gunbi-tang and Injin-oryung-san. Saeng gan gunbi-tang and Injin-oryung-san have been used to treat hepatic disease and have been known to have beneficial effects. After 3weeks on medication, the clinical symptoms and liver function improved. So, we report this case to bring more attention to the safety and toxicity of herbal medicine.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.510-519
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• 2022

Tofacitinib, a Janus kinase 1 and 3 inhibitor, is mainly metabolized by CYP3A1/2 and CYP2C11 in the liver. The drug has been approved for the chronic treatment of severe ulcerative colitis, a chronic inflammatory bowel disease. This study investigated the pharmacokinetics of tofacitinib in rats with dextran sulfate sodium (DSS)-induced ulcerative colitis. After 1-min of intravenous infusion of tofacitinib (10 mg/kg), the area under the plasma concentration-time curves from time zero to time infinity (AUC) of tofacitinib significantly increased by 92.3%. The time-averaged total body clearance decreased significantly by 47.7% in DSS rats compared with control rats. After the oral administration of tofacitinib (20 mg/kg), the AUC increased by 85.5% in DSS rats. These results could be due to decreased intrinsic clearance of the drug caused by the reduction of CYP3A1/2 and CYP2C11 in the liver and intestine of DSS rats. In conclusion, ulcerative colitis inhibited CYP3A1/2 and CYP2C11 in the liver and intestines of DSS rats and slowed the metabolism of tofacitinib, resulting in increased plasma concentrations of tofacitinib in DSS rats.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.375-383
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• 2013

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.37-46
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• 2018

Objectives : Liver disease is an inflammatory reaction caused by oxidative stress, viral, alcohol, and drug properties. Inflammatory reaction causes hepatitis and chronic hepatitis is persistent, it progresses to liver fibrogenesis and liver cancer. The aim of this study was to confirm the hepatoprotective effect of Tongyuhwalhyeol-tang(Tongqiaohuoxue Decoction) (TH) and Gamtongyuhawlhyeol-tang(GTH) in TAA-induced liver injury animal model. Methods : The antioxidant activities were evaluated through in vitro experiments, such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and 2, 2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, total polyphenol and total flavonoid content measurement. To confirm the liver protective effect, induced by Thioacetamide (TAA) for 3 days injection at 200 mg/kg rats. TH and GTH were treated 3 days at 200 mg/kg/day. The changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$), alanine aminotransferanse (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, expression of anti-inflammation, anti-oxidant related proteins were investigated by western blot analysis. Results : TH was inhibited the antioxidant activities. In the TAA-induced rat, TH decreased ROS, $ONOO^-$, ALT, AST level in serum. Inflammation related protein expressions increased in TAA-induced rat compared to normal rat. However, TH group inhibited the down expression of these proteins. Also, anti-oxidant related protein expressions increased in TH group compared TAA-induced rat. Conclusion : Therefor, these results suggested that TH provided hepatoprotective effects on the hepatic injury leading to the reduction of inflammatory response. In addition, the effect of TH was superior to that of GTH.

• Molecules and Cells
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• v.42 no.3
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• pp.200-209
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• 2019

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been used as promising tools for regenerative medicine, disease modeling, and drug screening. Traditional and common strategies for pluripotent stem cell (PSC) differentiation toward disease-relevant cell types depend on sequential treatment of signaling molecules identified based on knowledge of developmental biology. However, these strategies suffer from low purity, inefficiency, and time-consuming culture conditions. A growing body of recent research has shown efficient cell fate reprogramming by forced expression of single or multiple transcription factors. Here, we review transcription factor-directed differentiation methods of PSCs toward neural, muscle, liver, and pancreatic endocrine cells. Potential applications and limitations are also discussed in order to establish future directions of this technique for therapeutic purposes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.6
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• pp.418-421
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• 2018

The purpose of this study was to evaluate the changes of liver function test before and after treatment in patients admitted to Korean medicine hospital. We checked liver function test level (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin) of 147 patient who admitted in Korean medicine hospital from July 1, 2015 to June 30, 2018. The subjects were selected those who took herbal medicine continuously during the admission period and who performed liver function test on admission and before discharge. And the subjects were excluded those who had a history of liver and biliary disease at the time of admission or who took hepatoprotectants. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase significantly decreased compared with the values of admission(p<0.05), but total bilirubin and direct bilirubin were not significantly changed(p>0.05). On admission 31 patients(21.1%) had abnormal liver function and 6 patients(4.1%) had liver injury while 19 patients(12.9%) had abnormal liver function and 6 patients(4.1%) showed liver injury before discharge. This study suggests that herbal medicine may not injure liver function.