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Drug induced hepatitis

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https://www.readbyqxmd.com/read/29786562/application-of-hepatocyte-like-cells-to-enhance-hepatic-safety-risk-assessment-in-drug-discovery
#1
REVIEW
Dominic P Williams
Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29784840/oxidative-stress-and-first-line-antituberculosis-drug-induced-hepatotoxicity
#2
Wing Wai Yew, Kwok Chiu Chang, Denise P Chan
Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even rarely mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Confining to first-line antituberculosis drugs, this review addresses whether and how oxidative stress, and more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction, may contribute to the hepatotoxicity induced by them. Risk factors for such toxicity that have been identified, in addition to genetic factors, principally include old age, malnutrition, alcoholism, chronic hepatitis C and chronic hepatitis B infection, HIV infection and pre-existing liver disease...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29780579/managing-portal-hypertension-in-patients-with-liver-cirrhosis
#3
REVIEW
Tilman Sauerbruch, Robert Schierwagen, Jonel Trebicka
Portal hypertension is one cause and a part of a dynamic process triggered by chronic liver disease, mostly induced by alcohol or incorrect nutrition and less often by viral infections and autoimmune or genetic disease. Adequate staging - continuously modified by current knowledge - should guide the prevention and treatment of portal hypertension with defined endpoints. The main goals are interruption of etiology and prevention of complications followed, if necessary, by treatment of these. For the past few decades, shunts, mostly as intrahepatic stent bypass between portal and hepatic vein branches, have played an important role in the prevention of recurrent bleeding and ascites formation, although their impact on survival remains ambiguous...
2018: F1000Research
https://www.readbyqxmd.com/read/29778543/expression-of-a-functional-intrabody-against-hepatitis-c-virus-core-protein-in-escherichia-coli-and-silkworm-pupae
#4
Tatsuya Kato, Moeko Hasegawa, Takeshi Yamamoto, Takatsugu Miyazaki, Ryosuke Suzuki, Takaji Wakita, Tetsuro Suzuki, Enoch Y Park
It has been shown that the single-domain intrabody 2H9-L against the hepatitis C virus (HCV) capsid (core) protein inhibits the viral propagation and NF-κB promoter activity induced by the HCV core. In this study, 2H9-L fused with the FLAG tag sequence was expressed in both Escherichia coli and silkworm pupae and then purified. In addition, the full-length and its C terminal deletions of the HCV core protein, i.e., 1-123 amino acid residues (C123), 1-152 amino acid residues (C152), 1-177 amino acid residues (C177) and 1-191 amino acid residues (C191), were expressed as fusion proteins with a 6 × His tag at their N-terminus in E...
May 17, 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29778019/phoenix-dactylifera-protects-against-oxidative-stress-and-hepatic-injury-induced-by-paracetamol-intoxication-in-rats
#5
Gamal A Salem, Ahmed Shaban, Hussain A Diab, Wesam A Elsaghayer, Manal D Mjedib, Aomassad M Hnesh, Ravi P Sahu
The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group...
May 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29774767/the-role-of-hepatic-antioxidant-capacity-and-hepatobiliary-transporter-in-liver-injury-induced-by-isopsoralen-in-zebrafish-larvae
#6
Y Zhang, Y Zhang, J Li, Y Chen, L Han, Q He, J Chu, K Liu
Isopsoralen is the main component of the Chinese medicine psoralen, which has antitumour activity and can be used for the treatment of osteoporosis. However, the mechanism behind its hepatotoxicity has not yet been elucidated. In this study, the hepatotoxicity of isopsoralen was investigated using zebrafish. Isopsoralen treatment groups of 25, 50 and 100 μM were established. The mortality, liver morphology changes, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology and mRNA levels of liver injury-related genes in zebrafish larvae were measured...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29774570/high-mobility-group-box-1-drives-fibrosis-progression-signaling-via-the-receptor-for-advanced-glycation-end-products-in-mice
#7
Xiaodong Ge, Elena Arriazu, Fernando Magdaleno, Daniel J Antoine, Rouchelle Dela Cruz, Neil Theise, Natalia Nieto
BACKGROUND & RATIONALE: High-mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) increased in response to liver injury. Since HMGB1 is a ligand for the receptor for advanced glycation end-products (RAGE), we hypothesized that induction of HMGB1 could participate in the pathogenesis of liver fibrosis via RAGE cell-specific signaling mechanisms. RESULTS: liver HMGB1 protein expression correlated with fibrosis stage in patients with chronic Hepatitis C virus (HCV) infection, primary biliary cirrhosis (PBC) and alcoholic steatohepatitis (ASH)...
May 18, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29773081/long-term-familial-mediterranean-fever-remission-on-successful-hepatitis-c-virus-treatment-in-a-patient-not-responding-to-colchicine-a-case-report
#8
Manik Gemilyan, Gagik Hakobyan, Susanna Ananyan
BACKGROUND: Familial Mediterranean fever is an autosomal recessive disorder characterized by periodic febrile attacks of aseptic serositis and/or arthritis. The main treatment is colchicine which prevents attacks in the majority of patients except for a group of colchicine-resistant cases. Chronic hepatitis C is a viral infection causing chronic inflammation of liver tissue (hepatitis) which ultimately progresses to fibrosis and liver cirrhosis with a high chance of hepatocellular carcinoma...
May 18, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29771124/genistein-ameliorates-non-alcoholic-fatty-liver-disease-by-targeting-thromboxane-a2-pathway
#9
Wenzhe Wang, Junliang Chen, Jinyan Mao, Hongling Li, Mingfu Wang, Hao Zhang, Haitao Li, Wei Chen
Non-alcoholic fatty liver disease (NAFLD) is now a public health issue worldwide, but no drug has received approval yet. Genistein, an isoflavonoid derived from soybean, ameliorates high fat diet-induced NAFLD in mice, but the molecular underpinnings remain largely elusive. Arachidonic acid is a major ingredient of animal fats, and arachidonic acid cascade has been implicated in chronic inflammation. In this study, we investigated whether genistein against NAFLD by targeting arachidonic acid cascade. By using a mouse model, we showed that genistein supplementation improved high-fat diet induced NAFLD by normalizing hepatomegaly, liver steatosis, aminotransferase abnormalities and glucose tolerance...
May 17, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29765319/progression-and-regression-of-hepatic-lesions-in-a-mouse-model-of-nash-induced-by-dietary-intervention-and-its-implications-in-pharmacotherapy
#10
Zhi-Ming Ding, Yue Xiao, Xikun Wu, Haixia Zou, Shurong Yang, Yiyun Shen, Juehua Xu, Heather C Workman, Amy L Usborne, Haiqing Hua
Understanding of the temporal changes of hepatic lesions in the progression and regression of non-alcoholic steatohepatitis (NASH) is vital to elucidation of the pathogenesis of NASH, and critical to the development of a strategy for NASH pharmacotherapy. There are challenges in studying hepatic lesion progression and regression in NASH patients due to the slow development of NASH in humans, one being the requirement for multiple biopsies during the longitudinal follow-up. Here we studied lesion progression and regression in the diet-induced animal model of NASH by application or removal of the pathogenic diet for multiple time periods...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29765217/allergy-to-chlorpromazine-and-valproic-acid-following-carbamazepine-hypersensitivity-in-a-patient-with-an-hla-b-4601-allele
#11
Kumi Sakurada, Takeshi Kozaru, Kazuo Yamada, Masashi Nibuya, Kiyoshi Nagata, Eiji Suzuki
A 73-year-old man, exhibiting psychomotor excitement after traumatic brain injury, developed allergic cutaneous eruptions and hepatic inflammation that did not resolve after the cessation of carbamazepine (CBZ). Fusing maculopapular erythema was observed in the face, neck, presternal region, and bilaterally in the forearms and feet. A drug-induced lymphocyte stimulation test revealed hypersensitivity to chlorpromazine (CPZ) and valproic acid (VPA), as well as to CBZ. The allergic reaction with eosinophilia to CPZ and VPA was suspected to have emerged following CBZ hypersensitivity, since previous treatment with CPZ and VPA prior to the introduction of CBZ had not been associated with adverse reactions earlier in the course of treatment...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29760366/-contribution-of-chimeric-mice-with-a-humanized-liver-to-the-evaluation-of-pharmacology-toxicity-and-pharmacokinetics-in-drug-discovery-and-development
#12
Seigo Sanoh, Shigeru Ohta
To develop new drugs with high efficacy and safety, it is important to predict the pharmacological, toxicological, and pharmacokinetic profiles of drug candidates in humans. Chimeric mice with a humanized liver are mice in which human hepatocytes have been transplanted, such that mouse liver cells are replaced with human hepatocytes; these mice have been used as prediction models. Studies performed thus far indicate that chimeric mice with a humanized liver can be used for the prediction of human-specific metabolite formation and plasma concentration-time curves for several drugs...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29755923/epigenetic-alterations-impact-on-antipsychotic-treatment-in-elderly-patients
#13
Bryan M McClarty, Daniel W Fisher, Hongxin Dong
Purpose of the review: Antipsychotics are commonly prescribed for the treatment of psychosis as well as behavioral and psychological symptoms of dementia (BPSD) in elderly patients. However, elderly patients often experience decreased antipsychotic efficacy and increased side effects, though the mechanisms underlying these changes with age are not clear. Recent findings: Although aging can affect drug metabolism and clearance through changes in renal and hepatic function, additional pharmacokinetic and pharmacodynamic changes due to aging-induced epigenetic alterations also impact processes important for antipsychotic function...
March 2018: Current Treatment Options in Psychiatry
https://www.readbyqxmd.com/read/29753871/combinatorial-usage-of-fungal-polysaccharides-from-cordyceps-sinensis-and-ganoderma-atrum-ameliorate-drug-induced-liver-injury-in-mice
#14
Songtao Fan, Xiaojun Huang, Sunan Wang, Chang Li, Zhihong Zhang, Mingyong Xie, Shaoping Nie
This study investigated the possible protective effect of combined fungal polysaccharides (CFP), consisting of Cordyceps sinensis polysaccharides (CSP) and Ganoderma atrum polysaccharides (PSG) with well-defined structural characteristics, against cyclophosphamide (CTX)-induced hepatotoxicity in mice. Our results indicated CFP effectively prevented the liver injury by decreasing toxicity markers (aspartate transaminase, alanine aminotransferase and alkaline phosphatase). Further biochemical and molecular analysis indicated CSP particularly inhibited the activation of Toll-like receptor 9 (TLR9) and its related inflammatory signals, including pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 to modulate hepatic inflammation response...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29751151/different-administration-patterns-of-docosahexaenoic-acid-in-combating-cytotoxic-manifestations-due-to-arsenic-trioxide-acute-promyelocytic-leukemia-drug-induced-redox-imbalance-in-hepatocytes
#15
S Abhilash, R Siviyasankar, P Binu, P Arathi, R Harikumaran Nair
Docosahexaenoic acid (DHA) obtained from fish and plant sources is an essential dietary fatty acid and an important cell membrane structural component. The acute promyelocytic leukemia (APL) drug arsenic trioxide (As2 O3 ), causes hepatotoxicity. We evaluated the protective potential of DHA as pre/ combination/ post-administration patterns against As2 O3 induced toxicity. The therapeutic concentration of As2 O3 (10 µM) resulted in cytotoxicity with a significant (p < 0.05) variation from the control group...
May 8, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29749446/anesthetic-effects-of-isoflurane-and-the-molecular-mechanism-underlying-isoflurane%C3%A2-inhibited-aggressiveness-of-hepatic-carcinoma
#16
Jing Hu, Jingli Hu, Hongmei Jiao, Qingguo Li
Anesthesia is produced by drugs or other methods, and refers to the attenuation of pain via reversible suppression of neuronal transmission in the central and peripheral nervous systems, during surgery. Clinical investigations have indicated that the anesthetic action of isoflurane is efficient to alleviate pain during tumor resection clinical trials. In addition, it has been reported that isoflurane can induce caspase‑3 activation and is associated with apoptosis of tumor cells. The present study investigated the anesthetic effects and molecular mechanisms underlying isoflurane‑induced apoptosis in patients with hepatic carcinoma...
May 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29744372/recent-advances-in-drug-induced-hypersensitivity-syndrome-drug-reaction-with-eosinophilia-and-systemic-symptoms
#17
REVIEW
Hideaki Watanabe
Drug-induced hypersensitivity syndrome (DIHS), also termed as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multiorgan systemic reaction characterized by a close relationship with the reactivation of herpes virus. Published data has demonstrated that among patients with DIHS/DRESS, 75-95% have leukocytosis, 18.2-90% show atypical lymphocytes, 52-95% have eosinophilia, and 75-100% have hepatic abnormalities. Histologically, eosinophils were observed less frequently than we expected (20%)...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29744119/levetiracetam-induced-transaminitis-in-a-young-male-with-traumatic-brain-injury
#18
Vivekananda Rachamallu, Michael M Song, Jace M Reed, Manish Aligeti
Levetiracetam is a commonly prescribed antiepileptic drug for seizure prophylaxis in patients with traumatic brain injury (TBI). Levetiracetam metabolism has been reported to be non-dependent on hepatic cytochrome P450 (CYP450) isoenzyme system. Furthermore, levetiracetam and its metabolites are reported to be eliminated from systemic circulation via renal excretion. Therefore, due to its well-known renal clearance mechanism with no dosage adjustments recommended for hepatic impairment, levetiracetam is often chosen as the drug of choice in patients with suspected or ongoing hepatic dysfunction...
November 2017: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/29739616/schistosoma-egg-induced-liver-pathology-resolution-by-sm-p80-based-schistosomiasis-vaccine-in-baboons
#19
Loc Le, Adebayo J Molehin, Stewart Nash, Souad R Sennoune, Gul Ahmad, Workineh Torben, Weidong Zhang, Afzal A Siddiqui
Schistosomiasis remains a serious chronic debilitating hepato-intestinal disease. Current control measures based on mass drug administration are inadequate due to sustained re-infection rates, low treatment coverage and emergence of drug resistance. Hence, there is an urgent need for a schistosomiasis vaccine for disease control. In this study, we assessed the anti-pathology efficacy of Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine against schistosomiasis caused by infections with Schistosoma mansoni in baboons...
May 5, 2018: Pathology
https://www.readbyqxmd.com/read/29738702/mesalazine-an-osteopontin-inhibitor-the-potential-prophylactic-and-remedial-roles-in-induced-liver-fibrosis-in-rats
#20
A Ramadan, Nehal Afifi, Nemat Z Yassin, Rehab F Abdel-Rahman, Sahar S Abd El-Rahman, Hany M Fayed
Liver fibrosis is a major health issue leading to high morbidity and mortality. The potential anti-fibrotic activity and the effect of mesalazine on osteopontin (OPN), an extra cellular matrix (ECM) component were evaluated in TAA-induced liver fibrosis in rats. For this purpose, forty-two adult male Wistar rats were divided into six groups. All animals, except the normal control, were intraperitoneally injected with TAA (200 mg/kg) twice per week for 6 weeks. In the hepato-protective study, animals were administered mesalazine (50 and 100 mg/kg, orally) for 4 weeks before induction of liver fibrosis then concomitantly with TAA injection...
May 5, 2018: Chemico-biological Interactions
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