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Salvatore Grisanti, Deborah Cosentini, Valeria Tovazzi, Susanna Bianchi, Barbara Lazzari, Francesca Consoli, Elisa Roca, Alfredo Berruti, Vittorio D Ferrari
PURPOSE: Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity. METHODS: Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment...
March 15, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Marco Fiore, Sebastiano Leone, Alberto Enrico Maraolo, Emilio Berti, Giovanni Damiani
Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Systemic treatments, including methotrexate and cyclosporin, are associated with potential hepatotoxicity, due to either direct liver damage or immunosuppression or both immunomediated and a direct liver injury; therefore, treatment of patients with psoriasis poses a therapeutic challenge. The aim of this minireview is to help clinicians in the management of psoriatic patients who develop signs of liver dysfunction...
2018: BioMed Research International
Nora Freyer, Selina Greuel, Fanny Knöspel, Florian Gerstmann, Lisa Storch, Georg Damm, Daniel Seehofer, Jennifer Foster Harris, Rashi Iyer, Frank Schubert, Katrin Zeilinger
The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP ( p < 0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP ( p < 0...
March 15, 2018: Bioengineering
Wei Zhang, Zheng Dong, Xiujuan Chang, Cuihong Zhang, Guanghua Rong, Xudong Gao, Zhen Zeng, Chunping Wang, Yan Chen, Yihui Rong, Jianhui Qu, Ze Liu, Yinying Lu
Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl4 )-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl4 (v/v) for 6 h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS)...
March 14, 2018: Journal of Physiology and Biochemistry
Xue-Yang Jiang, Ting-Kai Chen, Jun-Ting Zhou, Si-Yu He, Hong-Yu Yang, Yao Chen, Wei Qu, Feng Feng, Hao-Peng Sun
Designing multitarget-directed ligands (MTDLs) is considered to be a promising approach to address complex and multifactorial maladies such as Alzheimer's disease (AD). The concurrent inhibition of the two crucial AD targets, glycogen synthase kinase-3β (GSK-3β) and human acetylcholinesterase ( h AChE), might represent a breakthrough in the quest for clinical efficacy. Thus, a novel family of GSK-3β/AChE dual-target inhibitors was designed and synthesized. Among these hybrids, 2f showed the most promising profile as a nanomolar inhibitor on both h AChE (IC50 = 6...
March 8, 2018: ACS Medicinal Chemistry Letters
Bassant M Barakat, Hebatalla I Ahmed, Hoda I Bahr, Alaaeldeen M Elbahaie
The current study aimed to investigate the potential protective role of boswellic acids (BAs) against doxorubicin- (DOX-) induced hepatotoxicity. Also, the possible mechanisms underlying this protection; antioxidant, as well as the modulatory effect on the Nrf2 transcription factor/hem oxygenase-1 (Nrf2/HO-1) pathway in liver tissues, was investigated. Animals were allocated to five groups: group 1: the saline control, group 2: the DOX group, animals received DOX (6 mg/kg, i.p.) weekly for a period of three weeks, and groups 3-5: animals received DOX (6 mg/kg, i...
2018: Oxidative Medicine and Cellular Longevity
Kevin Zarrabi, Shenhong Wu
BACKGROUND: Nivolumab is approved for the treatment of many cancers. This meta-analysis was conducted to determine the risk of hepatotoxicity with nivolumab therapy. METHODS: An analysis from all phase I-III clinical trials up to December 2016 examining nivolumab was conducted. Data on elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each trial. Incidence and relative risk (RR) were calculated using random- or fixed-effects models with 95% confidence intervals (CIs)...
March 14, 2018: Oncology
Katherine Plewes, Hugh W F Kingston, Aniruddha Ghose, Thanaporn Wattanakul, Md Mahtab Uddin Hassan, Md Shafiul Haider, Prodip K Dutta, Md Akhterul Islam, Shamsul Alam, Selim Md Jahangir, A S M Zahed, Md Abdus Sattar, M A Hassan Chowdhury, M Trent Herdman, Stije J Leopold, Haruhiko Ishioka, Kim A Piera, Prakaykaew Charunwatthana, Kamolrat Silamut, Tsin W Yeo, Sue J Lee, Mavuto Mukaka, Richard J Maude, Gareth D H Turner, Md Abul Faiz, Joel Tarning, John A Oates, Nicholas M Anstey, Nicholas J White, Nicholas P J Day, Md Amir Hossain, L Jackson Roberts, Arjen M Dondorp
Background: Acute kidney injury independently predicts mortality in falciparum malaria. It is not known whether acetaminophen's capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria. Methods: A phase 2, open-label, randomized controlled trial at two hospitals in Bangladesh was conducted to assess effects on renal function, safety, pharmacokinetic properties and pharmacodynamic effects of acetaminophen. Febrile patients ( >12 years) with severe and moderately severe falciparum malaria were randomly assigned to receive acetaminophen (1g 6-hourly for 72 hours) or no acetaminophen, as an adjunct to intravenous artesunate...
March 12, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
V Hepnarova, J Korabecny, L Matouskova, P Jost, L Muckova, M Hrabinova, N Vykoukalova, M Kerhartova, T Kucera, R Dolezal, E Nepovimova, K Spilovska, E Mezeiova, N L Pham, D Jun, F Staud, D Kaping, K Kuca, O Soukup
Novel tacrine-benzyl quinolone carboxylic acid (tacrine-BQCA) hybrids were designed based on multi-target directed ligands (MTLDs) paradigm, synthesized and evaluated in vitro as inhibitors of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE). Tacrine moiety is represented herein as 7-methoxytacrine, 6-chlorotacrine or unsubstituted tacrine forming three different families of seven members, i.e. 21 compounds in overall. Introducing BQCA, a positive modulator of M1 muscarinic acetylcholine receptors (mAChRs), the action of novel compounds on M1 mAChRs was evaluated via Fluo-4 NW assay on the Chinese hamster ovarian (CHO-M1WT2) cell line...
March 2, 2018: European Journal of Medicinal Chemistry
Faaiza Shahid, Zeba Farooqui, Farah Khan
Cisplatin (cis-diamminedichloroplatinum [II], CP) is most widely prescribed in chemotherapy and efficaciously treats diverse human cancers, with remission rates >90% in testicular cancers. However, clinical use of CP is associated with numerous untoward side effects, in particular, at the gastrointestinal level that reduces the therapeutic efficacy of CP and often results in withdrawal of its clinical usage in long term cancer chemotherapy. Substantial strides have been made to identify effective protective strategies against CP-induced nephrotoxicity, hepatotoxicity and ototoxicity...
March 9, 2018: European Journal of Pharmacology
Wolfgang Miehsler, Clemens Dejaco, Hans-Peter Gröchenig, Harry Fuchssteiner, Christoph Högenauer, Lili Kazemi-Shirazi, Harald Maier, Andreas Mayer, Alexander Moschen, Walter Reinisch, Wolfgang Petritsch, Reingard Platzer, Pius Steiner, Herbert Tilg, Harald Vogelsang, Heimo Wenzl, Gottfried Novacek
Anti-TNFα-antibodies have revolutionized the therapy of inflammatory bowel diseases and other immune-mediated inflammatory diseases. Due to the increasing application of these substances, the Working Group of Inflammatory Bowel Diseases of the Austrian Association of Gastroenterology and Hepatology intended to update their consensus report on the safe use of Infliximab (published in 2010) and to enlarge its scope to cover all anti-TNFα-antibodies. The present consensus report summarizes the current evidence on the safe use of anti-TNFα-antibodies and covers the following topics: general risk of infection, bacterial infections (i...
March 2018: Zeitschrift Für Gastroenterologie
Soraya Aroonvilairat, Chanthana Tangjarukij, Thiwaree Sornprachum, Papada Chaisuriya, Taweeratana Siwadune, Kavi Ratanabanangkoon
Most Thai orchid farmers heavily used pesticide mixtures, and were shown to have various hematologic/immunologic alterations. The present study investigated the effect of exposure of male Wistar rats to a mixture of three pesticides (chlorpyrifos, cypermethrin and captan) that are most often used by the farmers. Three groups of 10 rats were dermally exposed to three different doses (high, middle and low) for 28 consecutive days. The rats showed significant changes in body, liver, kidneys and adrenals weights...
March 2, 2018: Environmental Toxicology and Pharmacology
Kunal Gupta, Hongyue Wang, Sanjiv B Amin
The aim of this study was to evaluate the effect of intermittent parenteral copper supplementation (IPC) on serum copper status and biochemical and hematological measures of copper toxicity and deficiency in premature infants with parenteral nutrition (PN)-associated cholestasis (PNAC). We performed a prospective nested observational study in premature infants with PNAC who received IPC after the development of PNAC. Infants with chromosomal disorders, TORCH (toxoplasmosis, parvovirus, syphilis, rubella, cytomegalovirus, herpes, human immunodeficiency virus) infection, metabolic disorder, and/or surgical abnormality of the hepatobiliary system were excluded...
March 12, 2018: Nutrition in Clinical Practice
Peng Sun, Jing-Jie Zhu, Ting Wang, Qi Huang, Yu-Ren Zhou, Bang-Wei Yu, Hua-Liang Jiang, He-Yao Wang
As a widely used anti-gout drug, benzbromarone has been found to induce hepatic toxicity in patients during clinical treatment. Previous studies have reported that benzbromarone is metabolized via cytochrome P450, thus causing mitochondrial toxicity in hepatocytes. In this study, we found that benzbromarone significantly aggravated hepatic steatosis in both obese db/db mice and high fat diet (HFD)-induced obese (DIO) mouse models. However, benzbromarone had less effect on the liver of lean mice. It was found that the expression of mRNAs encoding lipid metabolism and some liver-specific genes were obviously disturbed in benzbromarone-treated DIO mice compared to the control group...
March 8, 2018: Biochimica et Biophysica Acta
Shi-Jun Liu, Zhi-Shu Tang, Zhi-Xin Liao, Chun-Li Cui, Hong-Bo Liu, Yan-Ni Liang, Yu Zhang, Hong-Bo Xu, Dong-Bo Zhang, Ya-Ting Zheng, Huan-Xian Shi, Shi-Ying Li
ETHNOPHARMACOLOGICAL RELEVANCE: Ligularia przewalskii (Maxim.) Diels (LP) (called zhangyetuowu in Chinese), is generally found in moist forest areas in the western regions of China. The root, leaves and flower of LP are utilized as a common traditional medicine in China. It has been utilized conventionally in herbal remedies for the remedy of haemoptysis, asthma, pulmonary phthisis, jaundice hepatitis, food poisoning, bronchitis, cough, fever, wound healing, measles, carbuncle, swelling and phlegm diseases...
March 8, 2018: Journal of Ethnopharmacology
Mehdi Ait Laaradia, Moulay Abdelmonaim El Hidan, Fatimazahra Marhoume, Btissam Bouimeja, Sara Oufquir, Zahra Sokar, Ali Boumezzough, Abderrahman Chait
The present study investigated the toxic effects of B. lienhardi venom, at the histological, hematological, biochemical and motor skill levels following a subcutaneous injection of different doses of venom. The LD50 of B. lienhardi scorpion venom was found to be 0.27 mg/Kg by subcutaneous injection route. The results clearly indicate that B. lienhardi venom induces massive tissue damages in the organs, such as lungs, heart, kidneys and liver together with hematological impairments manifested by decreased levels of both red and white series...
March 8, 2018: Toxicon: Official Journal of the International Society on Toxinology
Abhinav Vasudevan, Lauren Beswick, Antony B Friedman, Alicia Moltzen, James Haridy, Ajay Raghunath, Miles Sparrow, Daniel van Langenberg
AIMS: To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. METHODS: A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. RESULTS: Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance...
February 10, 2018: Digestive and Liver Disease
Shenhai Gong, Tian Lan, Liyan Zeng, Haihua Luo, Xiaoyu Yang, Na Li, Xiaojiao Chen, Zhanguo Liu, Rui Li, Sanda Win, Shuwen Liu, Hongwei Zhou, Bernd Schnabl, Yong Jiang, Neil Kaplowitz, Peng Chen
BACKGROUND & AIMS: Acetaminophen (APAP) induced hepatotoxicity is a leading cause of acute liver failure worldwide. It is well established that the liver damage induced by acetaminophen exhibits diurnal variation. However, the detailed mechanism for the hepatotoxic variation is not clear. Here we aimed to determine the relative contributions of gut microbiota in modulating the diurnal variation of hepatotoxicity induced by APAP. METHODS: Male Balb/C mice were treated with or without antibiotics and orally administrated a single dose of APAP (300 mg/kg) at ZT0 (when the light is on-start of resting period) and ZT12 (when the light is off-start of active period)...
March 7, 2018: Journal of Hepatology
Xiaoxuan Zhai, Zhenxiao Zhang, Wenwen Liu, Baoshan Liu, Rui Zhang, Wenjun Wang, Wen Zheng, Feng Xu, Jiali Wang, Yuguo Chen
Cyclophosphamide (CY) is a widely used chemotherapeutic agent that is associated with severe side effects, such as hepatotoxicity and nephrotoxicity. However, the extent, mechanisms and potential prevention and treatment strategies of CY-induced acute hepatotoxicity and nephrotoxicity are largely unknown. In this study, we determined the existence and extent of CY-induced acute hepatotoxicity and nephrotoxicity, and demonstrated the effect of ALDH2 on CY-induced acute tissue toxicity and related mechanisms...
March 7, 2018: Biochemical and Biophysical Research Communications
Michael Schloss, Daniel Becak, Sebastian T Tosto, Arash Velayati
BACKGROUND Levofloxacin covers a broad spectrum of pathogens and is readily prescribed by clinicians. Hepatotoxicity is a known but unusual complication of levofloxacin use. Here, we present a case of severe transaminitis caused by levofloxacin. CASE REPORT A young man in his thirties with a history of asthma, chronic alcoholism, methamphetamine intravenous drug abuse (IVDA), and non-compliant insulin-dependent diabetes mellitus (IDDM) presented to an emergency department with suicidal ideation. Vital signs were stable and the patient was noted to have cellulitis of the right forearm, for which cultures were drawn, and he received IV clindamycin...
March 10, 2018: American Journal of Case Reports
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