• Title/Summary/Keyword: DILI

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Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver

  • Heidari, Reza;Esmailie, Neda;Azarpira, Negar;Najibi, Asma;Niknahad, Hossein
    • Toxicological Research
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    • v.32 no.2
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    • pp.133-140
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    • 2016
  • Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

Case Report of a Lumbar Disc Herniation (LDH) Patient with Chronic Active Hepatitis B (만성 활동성 B형 간염 질환 환자의 요추간판 탈출증 치험례)

  • Jung, You-jin;Kang, Kyung-rae;Lee, Min-su;Choi, A-ryun;Kang, A-hyun;Han, Dong-kun;Song, Woo-sub;Lee, Hyung-chung
    • The Journal of Internal Korean Medicine
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    • v.37 no.2
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    • pp.374-380
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    • 2016
  • Objective: Although the incidence of chronic hepatitis B has decreased around the world due to widespread national preventative control measures, mortality from the same condition can increase if the condition leads to liver cancer or liver cirrhosis. In most cases, herbal medicine does not show any statistically significant effects related to liver damage, but preconceptions do exist that herbal medicine can be toxic and cause such liver damage. To investigate this situation, this study therefore investigated a patient with hepatitis B who had combined traditional Korean medicine therapy and the use of analgesic drugs during a hospitalization period.Method: A patient with hepatitis B was given combined traditional Korean medicine therapy and the use of analgesic drugs during a hospitalization period.Results: Within 26 days, the patient was free from liver damage during the hospitalization period. She was followed up with a liver function test and was discharged after her condition improved; she also reported decreased back pain.

Safety of Herbal Medicines on Liver Function in Functional Dyspepsia Patients: A Single-Center Retrospective Study (기능성 소화불량 환자의 간 기능에 대한 한약 투여의 안전성: 단일 센터 후향적 연구)

  • Aram Han;Chang-Yul Keum;Chae-Rim Yoon;Su-Hyun Choi;Dahee Jeong;Nahyun Jeong;Hae-in Jeong;Na-Yeon Ha;Jinsung Kim
    • The Journal of Internal Korean Medicine
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    • v.44 no.4
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    • pp.635-644
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    • 2023
  • Objectives: This study analyzed laboratory serum data results before and after patients took herbal medicine to confirm the clinical safety of herbal medicine. In addition, in the event of liver damage, the case was analyzed to confirm the characteristics of liver damage and the possibility of liver damage caused by herbal medicine. Methods: A retrospective chart review of the effects of herbal medicine on liver function in patients diagnosed with functional dyspepsia was conducted. The electronic medical records of 128 patients in a single hospital were reviewed. Results: The statistical analysis revealed a statistically significant decrease in liver function-related laboratory serum data after taking herbal medicine (p<0.05). In addition, among 128 patients, there were two cases of drug-induced liver injury (DILI) (1.56%). Conclusion: Taking herbal medicine prescribed by experts does not significantly affect liver function in patients with functional dyspepsia. Rather, the liver levels of the subjects showed a significant decrease after taking herbal medicine. To support these results, further large-scale multicenter prospective studies are necessary.

Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling

  • Canmin Zhu;Dili Wang;Chang Chang;Aofei Liu;Ji Zhou;Ting Yang;Yuanfeng Jiang;Xia Li;Weijian Jiang
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.3
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    • pp.239-252
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    • 2024
  • Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Safety of Prescribed Korean Herbal Medicine on Liver Function : Prospective Multi-center Pilot Study (한약 복용이 간기능에 미치는 영향 : 전향적 다기관 예비연구)

  • Yun, Young-Ju;Park, Jae-Heon;Paeck, Eun-Kyung;Park, Jae-Hyung;Jeong, Seul-Ki;Park, Hae-Mo;Lee, Sun-Dong;Shin, Byung-Cheul
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.3
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    • pp.715-722
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    • 2009
  • The aim of this study was to investigate the safety of short-term use of Korean herbal medicine (KHM; prescribed herbal medicine by doctors of traditional Korean medicine) on liver function. Three hundred eighty four outpatients who took KHM for various conditions were enrolled for multi-center, prospective observational study. Of them 237 patients completed questionnaire and were checked liver function (aspartic aminotransferase;AST, alanine aminotransferase;ALT, alkaline phosphatase;ALP, total bilirubin;t-Bil, direct bilirubin;d-Bil, gamma glutamyltranspeptidase;GGT, protein and albumin) before and after taking KHM (duration; 21.4${\pm}$10.0 days), and data were analysed statistically. Of the 213 patients showing normal liver function test (LFT) at baseline, 209 (98.1%) remained within the normal range at the second test while 3 (1.4%) revealed slight increase of LFT. Only one subject had raised LFT regarding level of liver injury without perceived symptoms. Twenty-four of 237 patients were abnormal at baseline, and 16 at the second testing. Of the patients taking KHM, only 4 changed from normal to abnormal while 12 from abnormal to normal in their LFT. There were no significant increase in LFT level between the first and second test, except in the t-Bil level, however, the change of t-Bil was small and within normal range. The current study showed that the use of KHM did not increase the frequency of abnormal LFTs, at least in the short term.