• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.4
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• pp.347-350
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• 2018

Drug-induced autoimmune hepatitis (DIAIH) is an increasingly recognized form of drug-induced liver injury that leads to a condition similar to idiopathic autoimmune hepatitis. A number of drugs have been associated with DIAIH, minocycline is one of the most well characterized. Minocycline is a semisynthetic tetracycline antibiotic used in the treatment of acne vulgaris. Minocycline-induced autoimmune hepatitis presents with serologic and histologic features similar to idiopathic autoimmune hepatitis. However, the natural history and outcomes of these two conditions differ significantly. The majority of patients with minocycline-induced autoimmune hepatitis experience complete resolution of symptoms after withdrawal of the medication. Some patients may require a short course of steroids and rarely use of an immunomodulator to achieve resolution of disease. Recurrence of symptoms is rare and typically only occurs with reintroduction of minocycline. It is important for primary care providers to consider minocycline-induced autoimmune hepatitis when liver injury develops during minocycline therapy.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.3
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• pp.131-140
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• 2022

Objectives This study aimed to investigate whether the concurrent use of conventional and herbal medications affects liver and kidney function, by examining blood test data. Methods We retrospectively reviewed the electronic medical records of 590 inpatients with musculoskeletal diseases between 2013 and 2017. We investigated cases of drug-induced liver injury (DILI) according to the Roussel Uclaf Causality Assessment Method criteria and cases of drug-induced kidney injury (DIKI) based on the Kidney Disease Improving Global Outcomes definition. Results One case (0.17%) of DILI and one case (0.17%) of DIKI were identified. Significant improvements in serum laboratory data were observed after the concurrent use of both types of medications (p<0.05). The kappa coefficients ranged from 0.26 to 0.72, indicating that the values after the concurrent use of conventional and herbal medications showed a fair similarity to the baseline values of the patients. The linear regression test showed that female sex and high body mass index (BMI) were risk factors for an increase in the serum blood levels of liver function parameters. Conclusions The concurrent use of conventional and herbal medications for musculoskeletal disorders is relatively safe; however, clinicians should exercise caution when prescribing these medications to female patients and patients with a high BMI because of their potential effect on hepatic function.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10413-10420
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• 2015

Side effects are an unavoidable consequence of chemotherapy drugs, during which liver injury often takes place. The current study was designed to investigate the protective effect of Astragalus polysaccharides (APS) against the hepatotoxicity induced by frequently-used chemical therapy agents, cyclophosphamide (CTX), docetaxel (DTX) and epirubicin (EPI)) in mice. Mice were divided into five groups, controls, low or high dose groups ($DTX_L$, $CTX_L$, $EPI_L$ or $DTX_H$, $CTX_H$, $EPI_H$), and low or high dose chemotherapeutics+APS groups ($DTX_L$+APS, $CTX_L$+APS, $EPI_L$+APS or $DTX_H$+APS, $CTX_H$+APS, $EPI_H$+APS). Controls were treated with equivalent normal saline for 28 days every other day; low or high dose group were intraperitoneal (i.p) injected with low or high doses of CTX, DTX and EPI for 28 days every other day; low or high dose chemotherapeutics+APS group were separately intraperitoneal (i.p) injected with chemotherapeutics for 28 days every other day and i.p with APS (100 mg/kg) for 7 days continually from the 22th to the 28th days. The body weight, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histopathological features, and ultrastructure morphological change of liver tissues, protein expression level of caspase-3 were estimated at different time points. With high dose treatment of DTX, CTX and EPI, weight gain was inhibited and serum levels of ALT and AST were significantly increased. Sections of liver tissue showed massive hepatotoxicity in $CTX_H$ group compared to the control group, including hepatic lobule disorder, granular and vacuolar degeneration and necrosis in hepatic cells. These changes were confirmed at ultrastructural level, including obvious pyknosis, heterochromatin aggregation, nuclear membrane resolution, and chondrosome crystal decrease. Western blotting revealed that the protein levels of caspase-3 increased in $CTX_H$ group. The low dose groups exhibited trivial hepatotoxicity. More interestingly, after 100 mg/kg APS, liver injury was redecued not only regarding serum transaminase activities (low or high dose chemotherapeutics+APS group), but also from pathological and ultrastructural changes and the protein levels of caspase-3 ($CTX_H$+APS group). In conclusion, DTX, CTX and EPI induce liver damage in a dose dependent manner, whereas APS exerted protective effects.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.4
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• pp.387-391
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• 2019

Tea is the most widely consumed beverage after water in the world. The consumption of iced tea has increased in Western countries and spiked among teenagers for enjoyment, freshening up and alertness. A teenager presented with symptoms of hepatitis. Liver ultrasound revealed sludge in the gallbladder. Laboratory investigations excluded all known causes of hepatotoxicity. Detail nutritional history revealed that the patient had been drinking 1.5-2 liters of black iced tea per day for the last three months. He was immediately advised to stop drinking any tea. Gradually all symptoms disappeared and two months after discontinuation of the tea, all liver enzymes returned to normal and the sludge in the gallbladder disappeared. This case report underlines the importance of a meticulous assessment of a child's dietary behavior when investigating a case of hepatotoxicity and raises awareness about the potential side effects of tea overconsumption.

• The Journal of Korean Obstetrics and Gynecology
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• v.36 no.4
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• pp.40-48
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• 2023

Objectives: The purpose of this study is to investigate safety of postpartum herbal medicine by assessing the effect of taking herbal medicine of postpartum period on liver function. Methods: A retrospective chart review was conducted on 167 mothers who underwent liver function tests (LFT) within 3 months before and after childbirth among mothers who gave birth at ○○ Hospital between January 1, 2016 and May 31, 2018. Mothers with abnormally elevated LFT during pregnancy were excluded. Among 167 women, 6 women are herbal-medicine-group took herbal medicine for 5-6 weeks during postpartum period, and 161 patients are general -group who did not take herbal medicine. LFT Variation of Subjects before and after childbirth were compared between the two groups. And subjects who had elevated liver levels above the normal range after delivery were classified separately, the characteristics and causes of changes in liver levels were analyzed, and the presence or absence of drug-induced liver damage was confirmed. Results: Among a total of 167 subjects, there were 5 women in the herbal-medicine-group and 150 women in the general-group who had changes in liver values within the normal range after childbirth. Aspartate transaminase (AST) change before and after childbirth in the herbal-medicine-group was 3.40±1.82, and AST change in the general-group was 2.92±8.59, showing no significant difference between the two groups (p=0.901). Increase of Alanine transaminase (ALT) before and after childbirth in the herbal-medicine-group was 5.60±3.65, and ALT change in the general-group was 8.01±11.81, showing no significant difference between the two groups (p=0.651). There were 12 subjects who had elevated AST, ALT above the normal range after delivery, including 1 in the herbal-medicine-group and 11 in the normal mothers group. Valuation of 1 Subject of the herbal-medicine-group before and after delivery was 17 IU/L of AST and 52 IU/L of ALT. Because results of AST, ALT is under the standard to diagnose to liver damage, she was observed without any treatment. However the cause of AST, ALT elevation was not found in the chart, she was receiving treatment for diabetes and hyperlipidemia. The general-group had an average increase of AST 35.64±22.67 IU/L and ALT 53.00±26.80 IU/L. As a result of analyzing the cause, there were direct causes such as autoimmune hepatitis, chronic hepatitis B, and acute pyelonephritis. Abnormal elevations in liver levels were also found in mothers with hypothyroidism, diabetes, and fever of unknown cause, although they were not direct causes. Conclusions: To investigate the safety of taking herbal medicines, we assess the variation in AST and ALT within 3 months before and after delivery in the herbal-medicine-group and general-group. There was no significant difference between two groups.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.344-353
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• 2020

This study aims to develop new potential therapeutic moracin M prodrugs acting on lung inflammatory disorders. Potential moracin M prodrugs (KW01-KW07) were chemically synthesized to obtain potent orally active derivatives, and their pharmacological activities against lung inflammation were, for the first time, examined in vivo using lipopolysaccharide (LPS)-induced acute lung injury model. In addition, the metabolism of KW02 was also investigated using microsomal stability test and pharmacokinetic study in rats. When orally administered, some of these compounds (30 mg/kg) showed higher inhibitory action against LPS-induced lung inflammation in mice compared to moracin M. Of them, 2-(3,5-bis((dimethylcarbamoyl)oxy)phenyl)benzofuran-6-yl acetate (KW02) showed potent and dose-dependent inhibitory effect on the same animal model of lung inflammation at 1, 3, and 10 mg/kg. This compound at 10 mg/kg also significantly reduced IL-1β concentration in the bronchoalveolar lavage fluid of the inflamed-lungs. KW02 was rapidly metabolized to 5-(6-hydroxybenzofuran-2-yl)-1,3-phenylene bis(dimethylcarbamate) (KW06) and moracin M when it was incubated with rat serum and liver microsome as expected. When KW02 was administered to rats via intravenous or oral route, KW06 was detected in the serum as a metabolite. Thus, it is concluded that KW02 has potent inhibitory action against LPS-induced lung inflammation. It could behave as a potential prodrug of moracin M to effectively treat lung inflammatory disorders.

• Herbal Formula Science
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• v.16 no.1
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• pp.117-130
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• 2008

Korean traditional medicine has been used for the treatment of the various diseases based on both oriental medicinal theory and clinical trials. Thus, the prescriptions of Korean traditional medicine would be useful for the development of new therapeutics. This research focuses on the fundamental study in Korean traditional prescriptions for the development of new hepatoprotective agents. We found two prescriptions. Injinho-Tang and Osumogwa-Tang, showed the significant DPPH free radical scavenging and hepatoprotective effect, respectively. It is well-known that free radical scavenging effect is related to the prevention of various pathological events including liver injury. This paper deals with hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, free radicals scavenging on both DPPH and superoxide of above two prescriptions. Hot water extract of Injinho-Tang did not show the significant hepatoprotective effect on tacrine-induced cytotoxicity in Hep G2 cells, however, it shows the significant scavenging effects for both DPPH and superoxide radicals. On the other hand, all of the hot water extracts of constituent herbal drugs in Injinho-Tang exhibited the promising protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Of these, water extract of Rhei Rhizoma showed the most prominent effect on tacrine-induced cytotoxicity in Hep G2 cells. Bioassay-guided fractionation of Rhei Rhizoma extract has furnished four compounds, and their chemical structures have been identified by comparison of their spectral data with those of literature as chrysophanol (1), emodin (2), 3,5-dihydroxy-4'- methoxystilbene (3), and rhapontigenin (4), respectively. Among the isolated compounds, compounds 2-4 revealed the significant hepatoprotective effect in vitro when their $EC_{50}$ values compare with that of silybin, as a positive control. It also exhibited that emodin possessed the most hepatoprotective effect among these active compounds. In case of Osumogwa-Tang, its hot water extract showed the moderate protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Hot water extract of Chaenomelis Fructus, one of the constituent herbal drug of this prescription, exhibited the significant hepatoprotective effect with $EC_{50}$ value of $7.8{\pm}0.1\;{\mu}g/ml$, however, it showed strong cytotoxicity in Hep G2 cells above the concentration of $25\;{\mu}g/ml$. It was revealed that both hot water extract of Evodiae Fructus and its butanol soluble fraction showed the moderate hepatoprotective effect but concentration-dependent activity in Hep G2 assay system. Two quinolone alkaloids, evocarpine and dihydroevocarpine, also tested for their hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, however, these two compounds derived from the Evodiae Fructus as the major constituents did not show in vitro hepatoprotective effect. From these results, it would be necessary to further isolation of its hepatoprotective compounds from the butanol soluble fraction of the hot water extract of Evodiae Fructus.