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Christina Jiun-Yu Tan, Grant E Sklar
INTRODUCTION: Paracetamol is the most common pharmaceutical agent implicated in toxic exposure in Singapore. This study aimed to describe the characteristics of paracetamol overdose in the adult population managed at a tertiary healthcare facility in Singapore. METHODS: Medical records of adult patients hospitalised with a diagnosis of paracetamol overdose at National University Hospital, Singapore, over a three-year period from January 2011 to December 2013 were retrospectively reviewed...
October 18, 2016: Singapore Medical Journal
Hatice Baş, Dilek Pandır, Suna Kalender
Furan forms as a result of thermal treatment of food and induces harmful effects on organisms. In our work, lycopene, furan, and a combination of the two were given to diabetic male rats for 28 days. Hematological changes, total protein and cholesterol, triglyceride, and albumin levels, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase activities of the serum, malondialdehyde levels, glutathione peroxidase, catalase, glutathione-S-transferase, superoxide dismutase activities, DNA damage in liver tissues and hepatic histopathological alterations were compared to a control group...
September 1, 2016: Arhiv za Higijenu Rada i Toksikologiju
Jeong-Wook Choi, In-Hye Kim, Young-Min Kim, Min-Kyeong Lee, Youn-Hee Choi, Taek-Jeong Nam
The present study investigated the protective effect of Pyropia yezoensis glycoprotein (PYGP) against chronic ethanol consumption‑mediated hepatotoxicity in rats. Male Sprague-Dawley rats (n=20; 6 weeks old) were randomly divided into four groups. The rats in each group were treated for 30 days with the following: i) CON group, distilled water only; ii) EtOH group, 20% ethanol 3.7 g/kg/BW; iii) EtOH+150 group, 20% ethanol 3.7 g/kg/BW+PYGP 150 mg/kg/BW; iv) EtOH+300 group, 20% ethanol 3.7 g/kg/BW+PYGP 300 mg/kg/BW...
October 11, 2016: Molecular Medicine Reports
Frank F Vincenzi, Philippe Lunetta
While SCUBA diving, a 44-year-old Caucasian patient had an abnormal cardiac rhythm, presumably Torsade de Pointes (TdP), during the initial descent to depth. Upon surfacing, she developed ventricular fibrillation and died. The patient had been treated for mild depression for nearly a year with citalopram 60 mg per day, a drug known to cause prolonged QT interval. She had also been treated with two potentially hepatotoxic drugs. Liver impairment causes selective loss of cytochrome P450 (CYP) 2C19 activity, the major pathway for metabolism of citalopram...
December 2015: Drug Saf Case Rep
Harriet Gaskell, Parveen Sharma, Helen E Colley, Craig Murdoch, Dominic P Williams, Steven D Webb
More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells...
June 1, 2016: Toxicology Research
Haifeng Teng, Meng Chen, Ansheng Zou, Haili Jiang, Jichun Han, Long Sun, Chao Feng, Ju Liu
OBJECTIVES: The objective of this study was to investigate the hepatoprotective effect of licochalcone B (LCB) in a mice model of carbon tetrachloride (CCl4)-induced liver toxicity. MATERIALS AND METHODS: Hepatotoxicity was induced in mice by a single subcutaneous injection (SC) of CCl4. The LCB was administered orally once a day for seven days (PO) as pretreatment at three doses of 1, 5, and 25 mg/kg/day. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA...
August 2016: Iranian Journal of Basic Medical Sciences
Mohamed Balaha, Samah Kandeel, Waleed Barakat
Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin...
October 13, 2016: Toxicology and Applied Pharmacology
Daniel Hanna, Ariane Emami Riedmaier, Kim S Sugamori, Denis M Grant
The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development...
October 13, 2016: Toxicology
Kuo Du, Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) hepatotoxicity is characterized by an extensive oxidative stress. However, its source, pathophysiological role and possible therapeutic potential if targeted, have been controversially described. Earlier studies argued for cytochrome P450-generated reactive oxygen species (ROS) during APAP metabolism, which resulted in massive lipid peroxidation and subsequent liver injury. However, subsequent studies convincingly challenged this assumption and the current paradigm suggests that mitochondria are the main source of ROS, which impair mitochondrial function and are responsible for cell signaling resulting in cell death...
October 4, 2016: Redox Biology
Chang-Bum Ahn, Jae-Young Je, Young-Sang Kim, Sun-Joo Park, Boo Il Kim
Chemical modification of chitosan is a promising method for the improvement of biological activity. In this study, chitosan-caffeic acid (CCA) was prepared and its in vitro hepatoprotective ability against hydrogen peroxide-induced hepatic damage in liver cells was evaluated. Treatment with CCA (50-400 µg/mL) did not show cytotoxicity and also significantly (p < 0.05) recovered cell viability against 650 µM hydrogen peroxide-induced hepatotoxicity. CCA treatment attenuated reactive oxygen species generation and lipid peroxidation in addition to increasing cellular glutathione level in cultured hepatocytes...
October 15, 2016: Molecular and Cellular Biochemistry
Francia C Díaz, Esteban Sáez-González, Salvador Benlloch, Diego Álvarez-Sotomayor, Isabel Conde, Begoña Polo, María García, María Rodríguez, Martín Prieto
:  Background and aims. Steroid-related hepatotoxicity has become one of the most relevant causes of drug induced liver cholestasis. Some patients do not improve after standard medical treatment (SMT) and may therefore require other approaches, like extracorporeal liver support. MATERIAL AND METHODS: We report four cases of patients with pruritus, abnormal liver function tests and biopsy-proven anabolic steroid-induced cholestasis who were unresponsive to SMT. They underwent treatment with albumin dialysis (Molecular Adsorbent Recirculating System -MARS®-)...
November 2016: Annals of Hepatology
Mohamed Benchekroun, Alejandro Romero, Javier Egea, Rafael León, Patrycja Michalska, Izaskun Buendia, Maria Luisa Jimeno, Daniel Jun, Jana Janockova, Vendula Sepsova, Ondrej Soukup, Oscar M Bautista-Aguilera, Bernard Refouvelet, Olivier Ouari, José Marco-Contelles, Lhassane Ismaili
Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), melatonin, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway...
October 13, 2016: Journal of Medicinal Chemistry
Reham H Mekky, Mostafa R Fayed, Mohamed R El-Gindi, Azza R Abdel-Monem, María Del Mar Contreras, Antonio Segura-Carretero, Essam Abdel-Sattar
Chickpea (Cicer arietinum) is a legume of the family Fabaceae, subfamily Faboideae. In Egypt, chickpea seeds are usually consumed at raw green and tender stage, or in the form of mature dry seeds. In our previous study, 'Giza 1' seeds exhibited stronger antioxidant activity and higher total phenol content than those from other Egyptian cultivars. In order to assess the biological potential of 'Giza 1' seeds in vivo, the extraction procedure was reproduced here. The extract was standardized using liquid chromatography coupled to diode array detector and tandem mass spectrometry (MS/MS) to evaluate their hepatoprotective effect on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and acute toxicity...
2016: Frontiers in Pharmacology
J Floehr, E Dietzel, C Schmitz, A Chappell, W Jahnen-Dechent
STUDY QUESTION: Does antisense oligonucleotide (ASO)-mediated down-regulation of serum fetuin-B cause an infertility-like fetuin-B gene deficiency in female mice? SUMMARY ANSWER: Pharmacological fetuin-B down-regulation by ASO therapy results in reversible infertility in female mice. WHAT IS KNOWN ALREADY: Female fetuin-B deficient (Fetub(-/-)) mice are infertile owing to premature zona pellucida (ZP) hardening. Enzyme activity studies demonstrated that fetuin-B is a potent and highly specific inhibitor of the zona proteinase ovastacin, which cleaves ZP protein 2 (ZP2) and thus mediates definitive ZP hardening...
October 12, 2016: Molecular Human Reproduction
Kana Yanagihara, Yujung Liu, Kei Kanie, Kazuo Takayama, Minako Okamura, Mitsuhi Hirata, Takayuki Fukuda, Mika Suga, Hiroki Nikawa, Hiroyuki Mizuguchi, Ryuji Kato, Miho K Furue
Functional hepatocytes derived from human pluripotent stem cells (hPSCs) have potential as tools for predicting drug-induced hepatotoxicity in the early phases of drug development. However, the propensity of hPSC lines to differentiate into specific lineages is reported to differ. The ability to predict low propensity of hPSCs to differentiate into hepatocytes would facilitate the selection of useful hPSC clones and substantially accelerate development of hPSC-derived hepatocytes for pharmaceutical research...
October 12, 2016: Stem Cells and Development
Pravin Rathi, Pravir Gambhire
Abdomen is involved in 11% of patients with extra-pulmonary tuberculosis; The most common site of involvement is the ileocaecal region, other locations of involvement, in order of descending frequency, are the ascending colon, jejunum, appendix, duodenum, stomach, oesophagus, sigmoid colon, and rectum. Apart from the basic work up, Investigations like CT scan, EUS, Capsule endoscopy, Balloon enteroscopy, Ascitic fluid ADA, TB-PCR, GeneXpert, Laproscopy are being increasingly used to diagnose tuberculosis.Therapy with standard antituberculous drugs is usually highly effective for intestinal TB...
February 2016: Journal of the Association of Physicians of India
Ilhem Rjeibi, Anouar Ben Saad, Najla Hfaiedh
OBJECTIVE: The liver plays a major role in detoxification and metabolism of toxic compound and xenobiotics like pesticides. Thereby, any type of modification in its function causes hepatotoxicity. So, the aim of this study was designed to assess the antioxidant and hepatoprotective effects of methanol extract Amaranthus spinosus seed (ASS) on liver injury induced by deltamethrin (DLM), a synthetic pyrethroid pesticide. MATERIALS AND METHODS: ASS was subjected to different phytochemical analyses including total phenolic and flavonoid content...
October 8, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ryo Mitsugi, Kyohei Sumida, Yoshiko Fujie, Robert H Tukey, Tomoo Itoh, Ryoichi Fujiwara
Trovafloxacin is an antibiotic that was withdrawn from the market relatively soon after its release due to the risk of hepatotoxicity. Trovafloxacin is mainly metabolized to its acyl-glucuronide by uridine 5'-diphosphate (UDP)-glucuronosyltransferase (UGT) 1A1. In this study, we examined whether the acyl-glucuronide is involved in the development of hepatotoxicity. A UGT1A1-induced cell model was developed and the toxicity of trovafloxacin acyl-glucuronide was evaluated. The UGT1A1-induced cell model was developed by treating HepG2 cells with chrysin for 48 h...
2016: Biological & Pharmaceutical Bulletin
S Wattanapokayakit, T Mushiroda, H Yanai, N Wichukchinda, C Chuchottawon, S Nedsuwan, A Rojanawiwat, S Denjanta, T Kantima, J Wongyai, W Suwankesawong, W Rungapiromnan, R Kidkeukarun, W Bamrungram, A Chaiwong, S Suvichapanich, S Mahasirimongkol, K Tokunaga
BACKGROUND: Anti-tuberculosis drug-induced liver injury (AT-DILI) is one of the most common forms of drug-induced liver injury (DILI) in high tuberculosis (TB) burden countries. Among anti-tuberculosis drugs, isoniazid is the main cause of hepatotoxicity in patients with AT-DILI. OBJECTIVE: To investigate the association of AT-DILI with N-acetyltransferase 2 (NAT2) genotype status in Thai TB patients. METHODS: We enrolled 53 patients diagnosed with AT-DILI and 85 patients who tolerated anti-tuberculosis treatment as controls...
October 2016: International Journal of Tuberculosis and Lung Disease
Lixia Chen, Huanbiao Mo, Ling Zhao, Weimin Gao, Shu Wang, Meghan M Cromie, Chuanwen Lu, Jia-Sheng Wang, Chwan-Li Shen
Pesticides, smoke, mycotoxins, polychlorinated biphenyls (PCBs), and arsenic are the most common environmental toxins and toxicants to humans. These toxins and toxicants may impact on human health at the molecular (DNA, RNA, or protein), organelle (mitochondria, lysosome, or membranes), cellular (growth inhibition or cell death), tissue, organ, and systemic levels. Formation of reactive radicals, lipid peroxidation, inflammation, genotoxicity, hepatotoxicity, embryotoxicity, neurological alterations, apoptosis, and carcinogenic events are some of the mechanisms mediating the toxic effects of the environmental toxins and toxicants...
May 27, 2016: Journal of Nutritional Biochemistry
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