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Drug induced liver dysfunction

Mianhuan Li, Yi Lv, Feng Chen, Xiaoyan Wang, Jiang Zhu, Hao Li, Jia Xiao
BACKGROUND: One of the major obstacles facing stem cell therapy is the limited number of functional stem cells available after transplantation due to the harsh microenvironment surrounding the damaged tissue. The aim of this study was to delineate the mechanistic involvement of lysophosphatidic acid receptors (LPARs) and sphingosine-1-phosphate receptors (S1PRs) in the regulation of anti-stress and transplantation efficacy of stem cells. METHODS: Human adipose-derived mesenchymal stem cells (hADMSCs) were treated with chemical toxin or ethanol to induce cell stress...
June 14, 2018: Stem Cell Research & Therapy
Ge Liu, Kai Wang, Shan Kuang, Ruobing Cao, Li Bao, Rui Liu, Hongwei Liu, Chaomin Sun
Cancer cells rewire their metabolism to satisfy the demands of uncontrolled proliferation and survival. The reprogramming of lipid metabolism supports tumor growth, metastasis, and therapy-resistance. Therefore, targeting lipid metabolic reprogramming is a potential cancer treatment strategy. We recently isolated the novel natural triterpene GL22 from Ganoderma leucocontextum, a traditional Chinese medicine. Here, we show that GL22 significantly inhibits the growth of the liver cancer cell line Huh7.5 in vitro and of Huh7...
June 7, 2018: Cell Death & Disease
Shulin Shan, Zhenyu Shen, Fuyong Song
Acetaminophen (APAP) is a widely used analgesic and antipyretic drug. APAP overdose can induce acute liver injury in humans, which is responsible for approximately 50% of total cases of acute liver failure in the United States and some European countries. Currently, the metabolism of APAP in the body has been extensively investigated; however, the exact mechanisms for APAP hepatotoxicity are not well understood. Recent studies have shown that mitochondrial dysfunction, oxidative stress and inflammatory responses play a critical role in the pathogenesis of APAP hepatotoxicity...
June 6, 2018: Archives of Toxicology
Yuanwei Liang, Wei Huang, Delong Zeng, Xiaoting Huang, Leung Chan, Chaoming Mei, Pengju Feng, Choon-Hong Tan, Tianfeng Chen
Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of novel anticancer drugs to enhance the cancer targeting effects and biocompatibility, and decrease toxic side effects. Camptothecin (CPT) demonstrated strong anticancer activity in clinical trials but also notorious adverse effects. In this study, we presented a smart targeted delivery system (Biotin-ss-CPT) that consists of cancer-targeted moiety (biotin), a cleavable disulfide linker (S-S bond) and the active drug CPT...
November 2018: Drug Delivery
Yong Ling, Qiu-Xing Yang, Yu-Ning Teng, Shi Chen, Wei-Jie Gao, Jing Guo, Pei-Ling Hsu, Yue Liu, Susan L Morris-Natschke, Chin-Chuan Hung, Kuo-Hsiung Lee
Fourteen novel amino-quinoline-5,8-dione derivatives (6a-h and 7a-h) were designed and synthesized by coupling different alkyl- or aryl-amino fragments at the C6- or C7-position of quinoline-5,8-dione. All target compounds showed antiproliferative potency in the low micromolar range in both drug sensitive HeLaS3 and multidrug resistant KB-vin cell lines. Compounds 6h, 6d, 7a, and 7d exhibited more potent antiproliferative effects than the other compounds. Especially, compounds 6d and 7d displayed NQO1-dependent cytotoxicity and competitive NQO1 inhibitory effects in both drug sensitive HeLaS3 and multidrug resistant KB-vin cell lines...
May 18, 2018: European Journal of Medicinal Chemistry
Marta Olivares, Audrey M Neyrinck, Sarah A Pötgens, Martin Beaumont, Nuria Salazar, Patrice D Cani, Laure B Bindels, Nathalie M Delzenne
AIMS/HYPOTHESIS: Dipeptidyl peptidase 4 (DPP-4) inhibitors are agents designed to increase the half-life of incretins. Although they are administered orally, little is known about their effects on the gut microbiota and functions, despite the fact that some bacteria present in the gut microbiota exhibit DPP-4-like activity. Our objective was to study the impact of the DPP-4 inhibitor vildagliptin on gut functions and the intestinal ecosystem in a murine model of obesity induced by a Western diet (WD)...
May 25, 2018: Diabetologia
Pei-Chun Chen, Chin-Chu Chen, Yaw-Bee Ker, Chi-Huang Chang, Charng-Cherng Chyau, Miao-Lin Hu
Antrodan, a unique protein-bound polysaccharide derived from the fungal mycelia of Antrodia cinnamomea , has been reported to exhibit antitumor and anti-metastatic effects on Lewis lung carcinoma (LLC) cells through direct action and immunomodulation in vitro. In this study, we investigated the combined treatment of antrodan with an anti-cancer drug-cisplatin-and its underlying molecular mechanisms of action in a mouse xenograft tumor model. C57BL/6 mice were implanted (s.c.) with LLCs for nine days, before administration with only antrodan (20 mg/kg and 40 mg/kg; p...
May 24, 2018: International Journal of Molecular Sciences
Dina S El-Agamy, Hamdi H Almaramhy, Nishat Ahmed, Bsmah Bojan, Waad D Alrohily, Mohamed A Elkablawy
BACKGROUND/AIMS: Phosphodiesterase-5 inhibitors have beneficial effects in multiple liver diseases possibly through the reduction of oxidative stress and inflammatory response. However, these effects have not yet been examined in cholestatic liver dysfunction. Hence, this study aimed to explore the ability of vardenafil, a known phosphodiesterase-5 inhibitor, to repress lithocholic acid (LCA)-induced cholestatic liver injury and investigate the possible molecular pathways. METHODS: Male Swiss albino mice were treated with LCA (0...
May 23, 2018: Cellular Physiology and Biochemistry
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
Chunxia Huang, Michael Garnet Irwin, Gordon Tin Chun Wong, Raymond Chuen Chung Chang
BACKGROUND: Systemic inflammation induces neuroinflammation and cellular changes such as tau phosphorylation to impair cognitive function, including learning and memory. This study uses a single model, laparotomy without any pathogen, to characterize these changes and their responses to anti-inflammatory treatment in the intermediate term. METHODS: In a two-part experiment, wild-type C57BL/6N mice (male, 3 month old, 25 ± 2 g) were subjected to sevoflurane anesthesia alone or to a laparotomy...
May 17, 2018: Journal of Neuroinflammation
Mingzhu Yan, Yazhen Huo, Shutao Yin, Hongbo Hu
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed...
April 22, 2018: Redox Biology
Sandip Patel, Bethan S Kilpatrick
Two-pore channels (TPCs) are Ca2+ -permeable endo-lysosomal ion channels subject to multi-modal regulation. They mediate their physiological effects through releasing Ca2+ from acidic organelles in response to cues such as the second messenger, NAADP. Here, we review emerging evidence linking TPCs to disease. We discuss how perturbing both local and global Ca2+ changes mediated by TPCs through chemical and/or molecular manipulations can induce or reverse disease phenotypes. We cover evidence from models of Parkinson's disease, non-alcoholic fatty liver disease, Ebola infection, cancer, cardiac dysfunction and diabetes...
May 7, 2018: Biochimica et Biophysica Acta
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
Antonio Riva, Shilpa Chokshi
Alcoholic liver disease (ALD) is an escalating global problem accounting for more than 3 million deaths annually. Bacterial infections are diagnosed in 25-47% of hospitalized patients with cirrhosis and represent the most important trigger for acute decompensation, multi-organ failure, septic shock and death. Current guidelines recommend intensive antibiotic therapy, but this has led to the emergence of multi-drug resistant bacteria, which are associated with increased morbidity and mortality rates. As such, there is a pressing need to explore new paradigms for anti-infective therapy and host-directed immunomodulatory therapies are a promising approach...
May 8, 2018: Hepatology International
Kotaro Matsumoto, Kentaro Kikuchi, Yusuke Kajiyama, Yuichi Takano, Masatoshi Mabuchi, Shinpei Doi, Koichiro Sato, Hiroshi Miyakawa, Ichiro Yasuda
An 81-year-old woman developed liver dysfunction after two months' treatment with direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection. She was positive for serum anti-nuclear antibody, with an elevated immunoglobulin G level. A liver biopsy revealed high-grade interface hepatitis and infiltrate of lymphocytes and plasma cells. DAA-associated drug-induced autoimmune hepatitis (DI-AIH) was considered. Her liver dysfunction improved after discontinuing DAA therapy and starting prednisolone treatment...
April 27, 2018: Internal Medicine
Sonia Rosa Veiga, Xuemei Ge, Carol A Mercer, María Isabel Hernández-Alvarez, Hala Elnakat Thomas, Javier Hernández-Losa, Santiago Ramón Y Cajal, Antonio Zorzano, George Thomas, Sara C Kozma
PURPOSE: Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
D Y Saad, M M Soliman, A A Mohamed, G B Youssef
The current study was aimed to evaluate the protective effect of Holothurian atra (HA) extract; naturally occurring marine resource, against methotrexate (MTX) induced testicular dysfunction. Mature rats received either MTX (20 mg/kg, intraperitoneally) or saline on the 7th day of experiment al design. Seven days prior and after MTX-injection, rats received HA at dose of 300 mg/kg intragastrically (HA + MTX group; HA group alone). Serum was extracted and testicular tissues were examined for the changes in serum biochemistry (liver & kidney biomarkers, testicular hormones and antioxidants), molecular and histopthological alterations using RT-PCR and immunohistochemistry...
April 23, 2018: Andrologia
Meegun Hong, Dae Hee Han, Jitaek Hong, Dong Joon Kim, Ki Tae Suk
Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite intensive research in the last two decades, there is currently no Food and Drug Administration-approved therapy for treating ALD. Several studies have demonstrated the importance of the gut-liver axis and gut microbiome on the pathogenesis of ALD. Alcohol may induce intestinal dysbiosis and increased intestinal permeability, which in turn result in increased levels of pathogen-associated molecular patterns such as lipopolysaccharide (LPS) and translocation of microbial products from the gut to the liver (bacterial translocation)...
April 23, 2018: Probiotics and Antimicrobial Proteins
Ruibing Feng, Yang Wang, Conghui Liu, Chunyan Yan, Hang Zhang, Huanxing Su, Jing X Kang, Chang-Zhen Shang, Jian-Bo Wan
Acetaminophen (APAP) overdose-induced hepatotoxicity is the most commonly cause of drug-induced liver failure characterized by oxidative stress, mitochondrial dysfunction, and cell damage. Therapeutic efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFA) in several models of liver disease is well documented. However, the impacts of n-3 PUFA on APAP hepatotoxicity are not adequately addressed. In this study, the fat-1 transgenic mice that synthesize endogenous n-3 PUFA and wild type (WT) littermates were injected intraperitoneally with APAP at the dose of 400 mg/kg to induce liver injury, and euthanized at 0 h, 2 h, 4 h and 6 h post APAP injection for sampling...
April 18, 2018: Biochemical Pharmacology
Karin Gmitterová, Michal Minár, Miroslav Žigrai, Zuzana Košutzká, Alice Kušnírová, Peter Valkovič
BACKGROUND: Hepatic encephalopathy may manifest by a wide spectrum of neuropsychiatric symptoms, including cognitive impairment, seizures or extrapyramidal symptoms. The liver transplant can lead to improvement of the signs of encephalopathy but subsequent immunosuppressive treatment might possess pronounced neurotoxicity. CASE PRESENTATION: We present a case report of a patient with chronic liver disease who developed signs of Parkinsonism after an orthotopic liver transplant, with consecutive immunosuppressant treatment with tacrolimus...
April 20, 2018: BMC Neurology
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