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mitochondrial hepatitis

Noelia Morales-Prieto, Julia Ruiz-Laguna, David Sheehan, Nieves Abril
The use of DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) in some countries, although regulated, is contributing to an increased worldwide risk of exposure to this organochlorine pesticide or its derivative p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene]. Many studies have associated p,p'-DDE exposure to type 2 diabetes, obesity and alterations of the reproductive system, but their molecular mechanisms of toxicity remain poorly understood. We have addressed this issue by using commercial microarrays based on probes for the entire Mus musculus genome to determine the hepatic transcriptional signatures of p,p'-DDE in the phylogenetically close mouse species Mus spretus...
March 16, 2018: Environmental Pollution
Yun Hu, Qinwei Sun, Yan Hu, Zhen Hou, Yibo Zong, Nagmeldin A Omer, Halima Abobaker, Ruqian Zhao
Background: We have shown previously that in ovo betaine injection can prevent nonalcoholic fatty liver induced by glucocorticoid exposure in chickens; yet it remains unknown whether feeding betaine to laying hens may exert similar effects in their progeny. Objective: In this study, we fed laying hens a betaine-supplemented diet, and the progeny were later exposed chronically to corticosterone (CORT) to test hepatoprotective effects and further elucidate underlying mechanisms...
March 1, 2018: Journal of Nutrition
Luke MacMillan, Garrett Tingley, Sara K Young, Kathy A Clow, Edward W Randell, Margaret E Brosnan, John T Brosnan
Background: Formate is produced in mitochondria via the catabolism of serine, glycine, dimethylglycine, and sarcosine. Formate produced by mitochondria may be incorporated into the cytosolic folate pool where it can be used for important biosynthetic reactions. Previous studies from our lab have shown that cobalamin deficiency results in increased plasma formate concentrations. Objective: Our goal was to determine the basis for elevated formate in vitamin B-12 deficiency...
March 1, 2018: Journal of Nutrition
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
Anna Lynnyk, Mariia Lunova, Milan Jirsa, Daria Egorova, Andrei Kulikov, Šárka Kubinová, Oleg Lunov, Alexandr Dejneka
Low-power laser irradiation of red light has been recognized as a promising tool across a vast variety of biomedical applications. However, deep understanding of the molecular mechanisms behind laser-induced cellular effects remains a significant challenge. Here, we investigated mechanisms involved in the death process in human hepatic cell line Huh7 at a laser irradiation. We decoupled distinct cell death pathways targeted by laser irradiations of different powers. Our data demonstrate that high dose laser irradiation exhibited the highest levels of total reactive oxygen species production, leading to cyclophilin D-related necrosis via the mitochondrial permeability transition...
March 1, 2018: Biomedical Optics Express
Ursula J Lemberger, Claudia D Fuchs, Christian Schöfer, Andrea Bileck, Christopher Gerner, Tatjana Stojakovic, Makoto M Taketo, Michael Trauner, Gerda Egger, Christoph H Österreicher
Background: Wnt/β-catenin signaling plays a crucial role in embryogenesis, tissue homeostasis, metabolism and malignant transformation of different organs including the liver. Continuous β-catenin signaling due to somatic mutations in exon 3 of the Ctnnb1 gene is associated with different liver diseases including cancer and cholestasis. Results: Expression of a degradation resistant form of β-catenin in hepatocytes resulted in 100% mortality within 31 days after birth...
February 16, 2018: Oncotarget
A C Van Erp, R A Rebolledo, D Hoeksma, N R Jespersen, P J Ottens, R Nørregaard, M Pedersen, C Laustsen, J G M Burgerhof, J C Wolters, J Ciapaite, H E Bøtker, H G D Leuvenink, B Jespersen
Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted)...
March 13, 2018: Scientific Reports
Yi-Yuan Zheng, Miao Wang, Xiang-Bing Shu, Pei-Yong Zheng, Guang Ji
AIM: To elucidate the potential role of autophagy and the protective effects of Jiang Zhi Granule (JZG) in metabolic stress-induced hepatocyte injury. METHODS: An in vitro and in vivo approach was used in this study. HepG2 cells were incubated in culture medium containing palmitate (PA; 0, 0.1, 0.2, 0.3, 0.4 or 0.5 mmol/L) and treated with or without JZG (100 μg/mL) for 24 h or 48 h, and the progression of autophagy was visualized by stable fluorescence-expressing cell lines LC3 and p62...
March 7, 2018: World Journal of Gastroenterology: WJG
Furkhan Ahmed Mohammed, Ayman I Elkady, Fareeduddin Quadri Syed, Muqtadir Baig Mirza, Khalid Rehman Hakeem, Saleh Alkarim
ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal herb, Anethum graveolens L. (dill) is one of the potent culinary herbs used as an alternative form of medicine worldwide. The unguent topical Oil from the aerial parts of A. graveolens was found to be effective in the management of uterus cancer in ethnomedicine has been reported. BACKGROUND: The incidence and mortality rates of Hepatocellular carcinoma (HCC) are steadily rising worldwide, especially, in underdeveloped and developing countries...
March 9, 2018: Journal of Ethnopharmacology
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
Dandan Huang, Baoqing Liu, Kai Huang, Kun Huang
Metabolic disorders, including obesity, non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and diabetes, are complex and progressive diseases. Enoyl coenzyme A hydratase 1 (Ech1) is an enzyme that participates in mitochondrial fatty acid β-oxidation; however, little is known regarding the significance of Ech1 in the pathogenesis of metabolic disorders. Here, we report that high-fat-diet (HFD)-induced and genetic obesity could increase Ech1 expression in mouse liver. The overexpression of Ech1 using adeno-associated virus (AAV2/8) ameliorated HFD-induced liver lipid accumulation and accompanying liver injury...
March 8, 2018: Biochemical and Biophysical Research Communications
Jeong-Min Hong, Sun-Mee Lee
AIMS: Heme oxygenase-1 (HO-1), an endogenous cytoprotective enzyme, is reported that can be localized in mitochondria under stress, contributing to preserve mitochondrial function. Mitochondrial quality control (QC) is essential to cellular health and recovery linked with redox homeostasis. Recent studies reported that phosphoglycerate mutase family member (PGAM) 5, a mitochondria-resident phosphatase, plays critical role in mitochondrial homeostasis. Therefore, we aim to investigate cytoprotective mechanisms of HO-1 in I/R-induced hepatic injury focusing on mitochondrial QC associated with PGAM5 signaling...
March 7, 2018: Life Sciences
Manon Viaud, Stoyan Ivanov, Nemanja Vujic, Madalina Duta-Mare, Lazaro-Emilio Aira, Thibault Barouillet, Elsa Garcia, François Orange, Isabelle Dugail, Isabelle Hainault, Christian Stehlik, Sandrine Marchetti, Laurent Boyer, Rodolphe Guinamard, Fabienne Foufelle, Andrea E Bochem, Kees G Hovingh, Edward B Thorp, Emmanuel L Gautier, Dagmar Kratky, Paul A Da Silva-Jardine, Laurent Yvan-Charvet
<u>Rationale:</u> Macrophages face a substantial amount of cholesterol following the ingestion of apoptotic cells and the lysosomal acid lipase (LIPA) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment. <u>Objective:</u> Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo. <u>Methods and Results:</u> We show that LIPA inhibition causes a defective efferocytic response due to impaired generation of 25-OHC and 27-OHC...
March 9, 2018: Circulation Research
Eungu Kang, Yoon-Myung Kim, Minji Kang, Sun-Hee Heo, Gu-Hwan Kim, In-Hee Choi, Jin-Ho Choi, Han-Wook Yoo, Beom Hee Lee
BACKGROUND: Fatty acid oxidation disorders (FAODs) include more than 15 distinct disorders with variable clinical manifestations. After the introduction of newborn screening using tandem mass spectrometry, early identification of FAODs became feasible. This study describes the clinical, biochemical and molecular characteristics of FAODs patients detected by newborn screening (NBS) compared with those of 9 patients with symptomatic presentations. METHODS: Clinical and genetic features of FAODs patients diagnosed by NBS and by symptomatic presentations were reviewed...
March 8, 2018: BMC Pediatrics
Lingyan Wu, Lina Zhang, Bohan Li, Haowen Jiang, Yanan Duan, Zhifu Xie, Lin Shuai, Jia Li, Jingya Li
Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic "brown-like" cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood...
2018: Frontiers in Physiology
Russell P Goodman, Sarah Calvo, Vamsi K Mootha
Compartmentalization is a fundamental design principle of eukaryotic metabolism.  Here, we review the compartmentalization of NAD+/NADH and NADP+/NADPH with a focus on the liver, an organ that experiences the extremes of biochemical physiology each day.  Historical studies of the liver, using classical biochemical  measurements of redox-coupled metabolites, have given rise to the view that mitochondrial NAD(H) pools tend to be oxidized and important for energy homeostasis, whereas cytosolic NADP(H) pools tend to be highly reduced for reductive biosynthesis...
March 7, 2018: Journal of Biological Chemistry
Lotte Kors, Elena Rampanelli, Geurt Stokman, Loes Butter, Ntsiki M Held, Nike Claessen, Per W B Larsen, Joanne Verheij, Coert J Zuurbier, Gerhard Liebisch, Gerd Schmitz, Stephen E Girardin, Sandrine Florquin, Riekelt H Houtkooper, Jaklien C Leemans
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction...
March 4, 2018: Biochimica et Biophysica Acta
Xi Du, Makafui Nyagblordzro, Lijun An, Xue Gao, Lemei Du, Yangyang Wang, Gregory Ondieki, Siambi Kikete, Xin He
Tripterigium wilfordii glycosides (TWG) demonstrate paramount bioactive effectiveness in the management of many autoimmune diseases, such as rheumatoid arthritis, psoriasis, and nephrotic syndrome. However, its side effects on the hepatic, nephrotic, reproductive, and cardiovascular systems have limited its immense therapeutic potentials. Triptolide (TP) and Celastrol (CL), the leading bioactive as well as toxic constituents of TWG, have been widely studied. These studies have documented the key mechanisms that trigger the toxic reactions and the precautionary measures that could prevent and reduce such reactions...
March 2, 2018: Current Drug Metabolism
Anna L Lang, Liya Chen, Gavin D Poff, Wen-Xing Ding, Russel A Barnett, Gavin E Arteel, Juliane I Beier
Vinyl chloride (VC), a common industrial organochlorine and environmental pollutant, has been shown to directly cause hepatic angiosarcoma and toxicant-associated steatohepatitis at high exposure levels. However, the impact of lower concentrations of VC on the progression of underlying liver diseases (e.g., nonalcoholic fatty liver disease [NAFLD]) is unclear. Given the high prevalence of NAFLD in the United States (and worldwide) population, this is an important concern. Recent studies by our group with VC metabolites suggest a potential interaction between VC exposure and underlying liver disease to cause enhanced damage...
March 2018: Hepatology Communications
Preeti Viswanathan, Yogeshwar Sharma, Priya Gupta, Sanjeev Gupta
OBJECTIVES: Acetaminophen hepatotoxicity is a leading cause of hepatic failure with impairments in liver regeneration producing significant mortality. Multiple intracellular events, including oxidative stress, mitochondrial damage, inflammation, etc., signify acetaminophen toxicity, although how these may alter cell cycle controls has been unknown and was studied for its significance in liver regeneration. MATERIALS AND METHODS: Assays were performed in HuH-7 human hepatocellular carcinoma cells, primary human hepatocytes and tissue samples from people with acetaminophen-induced acute liver failure...
March 5, 2018: Cell Proliferation
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