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Hepatotoxicity

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https://www.readbyqxmd.com/read/28108678/anti-tb-drug-concentrations-and-drug-associated-toxicities-among-tb-hiv-coinfected-patients
#1
C Sekaggya-Wiltshire, A von Braun, A U Scherrer, Y C Manabe, A Buzibye, D Muller, B Ledergerber, U Gutteck, N Corti, A Kambugu, P Byakika-Kibwika, M Lamorde, B Castelnuovo, J Fehr, M R Kamya
BACKGROUND: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. OBJECTIVES: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. METHODS: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment...
January 19, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28107620/chemical-interaction-of-protein-cysteine-residues-with-reactive-metabolites-of-methyleugenol
#2
Yukun Feng, Hui Wang, Qian Wang, Wenlin Huang, Ying Peng, Jiang Zheng
Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced toxicities. The objective of this study was to identify chemical identity of interactions of protein with reactive metabolites of ME. Modification of cysteine residues of protein was observed in microsomal incubations and mice after exposure to ME...
January 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28104448/metformin-and-low-dose-radiation-modulates-cisplatin-induced-oxidative-injury-in-rat-via-ppar-%C3%AE-and-mapk-pathways
#3
Heba H Mansour, Shereen M El Kiki, Shereen M Galal
: Cisplatin (CIS) is a chemotherapeutic agent used for therapy of many tumors and has been limited by its toxicity. The aim of this study was to investigate the role of Peroxisome proliferator-activated receptor-gamma (PPAR-γ), mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B(NFkB) in the pathogenesis of hepatic damage induced by CIS, and investigated the modulatory effect of metformin (MET) and/or low dose gamma radiation (LDR) on CIS-induced hepatotoxicity in rats...
January 16, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28104292/hepatic-prominin-1-expression-is-associated-with-biliary-fibrosis
#4
Marie V Nguyen, Jessica A Zagory, William H Dietz, Alex Park, Michael Fenlon, Menghan Zhao, Jiabo Xu, Ingrid Lua, Nirmala Mavila, Kenji Asahina, Kasper S Wang
BACKGROUND: Intrahepatic biliary fibrosis, as seen with cholestatic liver injuries such as biliary atresia, is mechanistically distinct from fibrosis caused by hepatocyte toxicity. We previously demonstrated the expansion of cells expressing the stem/progenitor cell marker Prominin-1, within regions of developing fibrosis in biliary atresia. Thus, we hypothesized that Prominin-1 expression is biliary fibrosis-specific. METHODS: Gene expression of Prominin-1 was analyzed in adult mice undergoing either cholestatic bile duct ligation or hepatotoxic carbon tetrachloride administration by quantitative polymerase chair reaction...
January 16, 2017: Surgery
https://www.readbyqxmd.com/read/28103938/the-gastro-protective-effects-of-cibotium-barometz-hair-on-ethanol-induced-gastric-ulcer-in-sprague-dawley-rats
#5
Nahla Saeed Al-Wajeeh, Maryam Hajerezaie, Suzita Mohd Noor, Mohammed Farouq Halabi, Nawal Al-Henhena, Ainnul Hamidah Syahadah Azizan, Sareh Kamran, Pouya Hassandarvish, Abdrabuh N Shwter, Hamed Karimian, Hapipah Mohd Ali, Mahmood Ameen Abdulla
BACKGROUND: Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups...
January 19, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28101470/protective-roles-of-n-acetyl-cysteine-and-or-taurine-against-sumatriptan-induced-hepatotoxicity
#6
Javad Khalili Fard, Hossein Hamzeiy, Mohammadreza Sattari, Mohammad Ali Eghbal
Purpose: Triptans are the drug category mostly prescribed for abortive treatment of migraine. Most recent cases of liver toxicity induced by triptans have been described, but the mechanisms of liver toxicity of these medications have not been clear. Methods: In the present study, we obtained LC50 using dose-response curve and investigated cell viability, free radical generation, lipid peroxide production, mitochondrial injury, lysosomal membrane damage and the cellular glutathione level as toxicity markers as well as the beneficial effects of taurine and/or N-acetyl cysteine in the sumatriptan-treated rat parenchymal hepatocytes using accelerated method of cytotoxicity mechanism screening...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28101469/concurrent-inflammation-augments-antimalarial-drugs-induced-liver-injury-in-rats
#7
Hossein Niknahad, Reza Heidari, Roya Firuzi, Farzaneh Abazari, Maral Ramezani, Negar Azarpira, Massood Hosseinzadeh, Asma Najibi, Arastoo Saeedi
Purpose: Accumulating evidence suggests that drug exposure during a modest inflammation induced by bacterial lipopolysaccharide (LPS) might increase the risk of drug-induced liver injury. The current investigation was designed to test if antimalarial drugs hepatotoxicity is augmented in LPS‑treated animals. Methods: Rats were pre-treated with LPS (100 µg/kg, i.p). Afterward, non-hepatotoxic doses of amodiaquine (25, 50 and 100 mg/kg, oral) and chloroquine (25, 50 and 100 mg/kg, oral) were administered. Results: Interestingly, liver injury was evident only in animals treated with both drug and LPS as estimated by pathological changes in serum biochemistry (ALT, AST, LDH, and TNF-α), and liver tissue (severe hepatitis, endotheliitis, and sinusoidal congestion)...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28099758/melatonin-alleviates-cadmium-induced-liver-injury-by-inhibiting-the-txnip-nlrp3-inflammasome
#8
Zhengwang Cao, Yiliang Fang, Yonghui Lu, Dunxian Tan, Changhong Du, Yuming Li, Qinlong Ma, Junmei Yu, Mengyan Chen, Chao Zhou, Liping Pei, Lei Zhang, Haiying Ran, Mindi He, Zhengping Yu, Zhou Zhou
Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In the present study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death...
January 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28095910/profile-of-bioactive-compounds-in-nymphaea-alba-l-leaves-growing-in-egypt-hepatoprotective-antioxidant-and-anti-inflammatory-activity
#9
Riham Omar Bakr, Mona Mohamed El-Naa, Soumaya Saad Zaghloul, Mahmoud Mohamed Omar
BACKGROUND: Nymphaea alba L. represents an interesting field of study. Flowers have antioxidant and hepatoprotective effects, rhizomes constituents showed cytotoxic activity against liver cell carcinoma, while several Nymphaea species have been reported for their hepatoprotective effects. Leaves of N. alba have not been studied before. Therefore, in this study, in-depth characterization of the leaf phytoconstituents as well as its antioxidant and hepatoprotective activities have been performed where N...
January 17, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28095673/a-comparative-study-of-hepatotoxicity-of-pyrrolizidine-alkaloids-retrorsine-and-monocrotaline
#10
Xiaojing Yang, Weiwei Li, Ying Sun, Xiucai Guo, Wenlin Huang, Ying Peng, Jiang Zheng
Many pyrrolizidine alkaloids (PAs) can cause liver injury in animals and humans. Different hepatotoxic PAs can produce similar hepatotoxic effects, but the degree of their toxicities may vary widely. Retrorsine (RTS) and monocrotaline (MCT) share the same core structure (retronecine) and similar metabolic activation pathway. RTS and MCT both produced liver injury but the former was more hepatotoxic than the latter. Enzyme kinetic study demonstrated that the value of Vmax/Km for RTS was 5.5-fold larger than that of MCT...
January 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28092099/calmodulin-binding-to-death-receptor-5-mediated-death-inducing-signaling-complex-in-breast-cancer-cells
#11
Romone M Fancy, Harrison Kim, Tong Zhou, Kurt R Zinn, Donald J Buchsbaum, Yuhua Song
Activation of death receptor-5 (DR5) leads to the formation of death inducing signaling complex (DISC) for apoptotic signaling. TRA-8, a DR5 specific agonistic antibody, has demonstrated significant cytotoxic activity in vitro and in vivo without inducing hepatotoxicity. Calmodulin (CaM) that is overexpressed in breast cancer plays a critical role in regulating DR5-mediated apoptosis. However, the mechanism of CaM in regulating DR5-mediated apoptotic signaling remains unknown. In this study, we characterized CaM binding to DR5-mediated DISC for apoptosis in TRA-8 sensitive breast cancer cell lines using co-immunoprecipitation, fluorescence microscopic imaging, caspase signaling analysis and cell viability assay...
January 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28090653/genome-wide-study-links-pnpla3-variant-with-elevated-hepatic-transaminase-after-acute-lymphoblastic-leukemia-therapy
#12
Yiwei Liu, Christian A Fernandez, Colton Smith, Wenjian Yang, Cheng Cheng, John C Panetta, Nancy Kornegay, Chengcheng Liu, Laura B Ramsey, Seth E Karol, Laura J Janke, Eric C Larsen, Naomi Winick, William L Carroll, Mignon L Loh, Elizabeth A Raetz, Stephen P Hunger, Meenakshi Devidas, Jun J Yang, Charles G Mullighan, Jinghui Zhang, William E Evans, Sima Jeha, Ching-Hon Pui, Mary V Relling
Remission induction therapy for acute lymphoblastic leukemia (ALL) includes medications that may cause hepatotoxicity, including asparaginase. We used a genome-wide association study (GWAS) to identify loci associated with elevated alanine transaminase (ALT) levels after induction therapy in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols. Germline DNA was genotyped using arrays and exome sequencing. Adjusting for age, body mass index, ancestry, asparaginase preparation and dosage, the PNPLA3 rs738409 (C>G) I148M variant, previously associated with fatty liver disease risk, had the strongest genetic association with ALT (P = 2...
January 16, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28089783/characterization-of-rat-or-human-hepatocytes-cultured-in-microphysiological-systems-mps-to-identify-hepatotoxicity
#13
Shih-Yu Chang, Jenna L Voellinger, Kirk P Van Ness, Brian Chapron, Rachel M Shaffer, Thomas Neumann, Collin C White, Terrance J Kavanagh, Edward J Kelly, David L Eaton
The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc...
January 12, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28088791/sinomenine-hydrochloride-inhibits-breast-cancer-metastasis-by-attenuating-inflammation-related-epithelial-mesenchymal-transition-and-cancer-stemness
#14
Xiao Li, Pingping Li, Chao Liu, Yu Ren, Xiaojiang Tang, Ke Wang, Jianjun He
Sinomenine hydrochloride (SH) has been investigated for its anti-tumor growth effect. We have previously reported that SH inhibited breast cancer cell proliferation via MAPKs signaling. However, whether SH could inhibit tumor metastasis has not been fully explored. In this study, we found that SH suppressed the metastasis potential of breast cancer cells. The wound healing and transwell assays showed that SH inhibited the migration and invasion ability of both 4T1 and MDA-MB-231 breast cancer cells. The orthotopic mouse model of 4T1 and the experimental mouse model of MDA-MB-231-luc (MDA-MB-231 cell line expressing firefly luciferase) demonstrated that SH treatment inhibited breast cancer metastasis by inhibiting epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties without obvious hepatotoxicity and renal toxicity...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088388/activation-of-gr-but-not-pxr-by-dexamethasone-attenuated-acetaminophen-hepatotoxicities-via-fgf21-induction
#15
Saurabh G Vispute, Pengli Bu, Yuan Le, Xingguo Cheng
Glucocorticoid receptor (GR) signaling is indispensable for cell growth and development, and plays important roles in drug metabolism. Fibroblast growth factor (Fgf) 21, an important regulator of glucose, lipid, and energy metabolism, plays a cytoprotective role by attenuating toxicities induced by chemicals such as dioxins, acetaminophen (APAP), and alcohols. The present study investigates the impact of dexamethasone (DEX)-activated GR on Fgf21 expression and how it affects the progression of APAP-induced hepatotoxicity...
January 11, 2017: Toxicology
https://www.readbyqxmd.com/read/28088257/clinical-and-experimental-research-in-antituberculosis-drug-induced-hepatotoxicity-a-review
#16
REVIEW
Udhaya Lavinya Baskaran, Evan Prince Sabina
Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity, its underlying mechanisms and alternative therapies for the same...
January 2017: Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28086886/biochemical-mechanism-underlying-hypertriglyceridemia-and-hepatic-steatosis-hepatomegaly-induced-by-acute-schisandrin-b-treatment-in-mice
#17
Yi Zhang, Jing Zhao, Shu-Feng Zhou, Zhi-Ling Yu, Xiao-Yan Wang, Pei-Li Zhu, Zhu-Sheng Chu, Si-Yuan Pan, Ming Xie, Kam-Ming Ko
BACKGROUND: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. METHODS: Male ICR mice were given a single oral dose of Sch B (0...
January 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28086854/in-vitro-assessment-of-hepatoprotective-agents-against-damage-induced-by-acetaminophen-and-ccl4
#18
Liliana Torres González, Noemí Waksman Minsky, Linda Elsa Muñoz Espinosa, Ricardo Salazar Aranda, Jonathan Pérez Meseguer, Paula Cordero Pérez
BACKGROUND: In vitro bioassays are important in the evaluation of plants with possible hepatoprotective effects. The aims of this study were to evaluate the pretreatment of HepG2 cells with hepatoprotective agents against the damage induced by carbon tetrachloride (CCl4) and paracetamol (APAP). METHODS: Antioxidative activity was measured using an assay to measure 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The in vitro hepatotoxicity of CCl4 and APAP, and the cytotoxic and hepatoprotective properties of silymarin (SLM), silybinin (SLB), and silyphos (SLP) were evaluated by measuring cell viability; activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH); total antioxidant capacity (TAOxC); and reduced glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde (MDA) levels)...
January 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28086769/effect-of-ginseng-extract-on-the-tgf-%C3%AE-1-signaling-pathway-in-ccl4-induced-liver-fibrosis-in-rats
#19
Mohamed M Hafez, Sherifa S Hamed, Manal F El-Khadragy, Zeinab K Hassan, Salim S Al Rejaie, Mohamed M Sayed-Ahmed, Naif O Al-Harbi, Khalid A Al-Hosaini, Mohamed M Al-Harbi, Ali R Alhoshani, Othman A Al-Shabanah, Shakir Dekhal Alsharari
BACKGROUND: Liver diseases are major global health problems. Ginseng extract has antioxidant, immune-modulatory and anti-inflammatory activities. This study investigated the effect of ginseng extract on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Male Wistar rats were divided into four groups: control group, ginseng group, CCl4 group and CCl4 + ginseng group. Liver injury was induced by the intraperitoneal (I.P) injection of 3 ml/kg CCl4 (30% in olive oil) weekly for 8 weeks...
January 13, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28081586/a-case-of-levocetirizine-induced-liver-injury
#20
Moon Chan Jung, Ja Kyung Kim, Jae Yeon Cho, Jae Won Song, Bohyun Lee, Ji Won Park, Jinwon Seo, Sung Eun Kim
Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis...
December 2016: Clinical and Molecular Hepatology
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