berghei NK65, on day 17 post-mating. Nitric oxide and liver health large number of study subjects Nitrjc needed for further live of these results. Using the same methodology, our group has confirmed these findings by identifying eNOS expression in isolated primary hepatocytes from WT mice using magnetic-activated cell sorting and immunofluorescence Sheldon et al.

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Mimura, I. Cytoglobin, a novel globin, plays an antifibrotic role in the kidney. Am J Physiol Renal Physiol. Download references. We thank Dr. Keiko Iwaisako for her technical advises and Dr. Kazuo Ikeda for his helpful discussion. TTVT awarded the Japanese Government Scholarship student for PhD course.

LTTT received a Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science J NK received a Grant-in-Aid for Scientific Research from JSPS No. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.

Synthetic Biology Laboratory, Graduate School of Medicine, Osaka City University, Osaka, Japan. You can also search for this author in PubMed Google Scholar. and L.

studied the concept and design, acquired data, analysed and interpreted data, performed all of the experiments, drafted the manuscript and obtained funding. critically revised the manuscript for important intellectual content, and supervised the study.

contributed to the study concept and design, drafted the manuscript, performed critical revisions of the manuscript for important intellectual content, obtained funding and supervised the study. All authors had final approval of the submitted version.

Correspondence to Norifumi Kawada. This work is licensed under a Creative Commons Attribution 4. Reprints and permissions. Van Thuy, T. Sci Rep 7 , Download citation. Received : 20 October Accepted : 29 December Published : 03 February Anyone you share the following link with will be able to read this content:.

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nature scientific reports articles article. Download PDF. Subjects Cholestasis Liver fibrosis. Abstract This study clarified the role of Cygb, the fourth globin in mammals originally discovered in rat hepatic stellate cells HSCs , in cholestatic liver disease.

Introduction Cholestatic liver disease is caused by the dysregulated production and excretion of bile from the liver to duodenum, which induces jaundice and the injury of the bile duct and hepatocytes, leading to biliary fibrosis, cirrhosis, and liver failure if persisted 1.

Full size image. Figure 2: Effect of Cygb deficiency on inflammation and cell death in acute BDL. Figure 3: Effect of Cygb deficiency in the expression of bile transporters and CD10 in acute BDL mice. Discussion Loss of Cygb in HSCs aggravates hepatocyte damage under BDL by dysregulation of NO Cygb is expressed in pericytes but not in the epithelial cells of all organs 6.

Loss of Cygb augments inflammation and oxidative stress under BDL In cholestatic liver disease, bile acids are inflammagens that stimulate hepatocytes to produce proinflammatory mediators, promoting the accumulation of neutrophils and other immune cells Methods Animal Studies All mice received humane care according to Guide for the Care and Use of Laboratory Animals, National Institutes of Health.

Bilirubin assay Bilirubin in serum was measured by a spectrophotometric assay by using Bilirubin Assay Kit BioAssay Systems, CA, USA according to the assay protocol.

Hydroxyproline assay Hydroxyproline content of the liver was measured by a spectrophotometric assay by using Hydroxyproline Assay Kit BioVision, CA, USA as previously described MDA assay Oxidative stress was assessed by measuring malondialdehyde MDA , the end products of lipid peroxidation.

Caspase 3 activity assay The caspase 3 activity is one of important hallmarks to assess apoptosis pathway. Quantitative Real-Time PCR The miRNeasy Mini Kit Qiagen, Valencia, CA, USA was used to extract total RNA from cells and liver tissues. Additional Information How to cite this article : Thuy, T.

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Download references. The English in this document has been checked by at least two professional editors, both native speakers of English.

This work was supported by a Grant—in—Aid for Scientific Research C from JSPS to M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Department of Infectious Diseases, Kyorin University School of Medicine, 6—20—2 Shinkawa, Mitaka, Tokyo, —, Japan.

Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan. Department of Molecular Pathology, Tokyo Medical University, Tokyo, —, Japan.

Department of Environmental Science, School of Life and Environmental Science, Azabu University, Kanagawa, , Japan. You can also search for this author in PubMed Google Scholar.

MN designed research; MN, TF and SM performed research; MN, TF, JM and FK analyzed data; and MN and FK wrote the paper. All authors read and approved the final manuscript. Correspondence to Mamoru Niikura. The experiments were approved by the Experimental Animal Ethics Committee of Kyorin University School of Medicine, Tokyo, and all experiments were performed in accordance with guidelines and regulations of animal experimentation at Kyorin University.

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Comparative proteomic analysis of livers of immunized pregnant mice infected with P. Livers were obtained from unimmunized pregnant mice without infection naïve pregnant mice and unimmunized non-pregnant mice without infection naïve virgin mice , and immunized pregnant and non-pregnant mice infected with P.

Proteins showing one or two peptide spectral matches were excluded. Protein levels were normalized to actin, cytoplasmic 1 accession: P Nitric oxide produced by inducible nitric oxide synthase iNOS is not involved in the development of liver injury during primary infection with lethal malaria parasites.

Unimmunized wild-type WT and iNOS-knockout KO female mice were placed with male WT mice for 1 day. B—E Liver tissue staining with haematoxylin and eosin. Livers were obtained from mice on day 7 post-infection. B Unimmunized non-pregnant WT mice infected with P.

C Unimmunized pregnant WT mice infected with P. D Unimmunized non-pregnant iNOS-KO mice infected with P. E Unimmunized pregnant iNOS-KO mice infected with P.

Comparative proteomic analysis of livers of immunized pregnant inducible nitric oxide synthase-knockout iNOS-KO mice infected with P. Livers were obtained from immunized pregnant mice infected with P. Open Access This article is licensed under a Creative Commons Attribution 4. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.

If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and permissions.

Niikura, M. et al. The association between acute fatty liver disease and nitric oxide during malaria in pregnancy. Malar J 20 , Download citation. Received : 28 September Accepted : 01 December Published : 14 December Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Research Open access Published: 14 December The association between acute fatty liver disease and nitric oxide during malaria in pregnancy Mamoru Niikura ORCID: orcid.

Abstract Background Liver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear. Methods To understand the pathogenesis of liver disease during malaria in pregnancy, comparative proteomic analysis of the liver in a mouse model of malaria in pregnancy was performed.

Results Decreased levels of mitochondrial and peroxisomal proteins were observed in the livers of pregnant mice infected with the lethal rodent malaria parasite Plasmodium berghei strain NK Conclusions In this study, a causative role of iNOS in liver disease associated with microvesicular fatty infiltration during malaria in pregnancy was demonstrated.

Background Individuals living in malaria-endemic regions acquire protective immunity against malaria parasites and often show asymptomatic infection. Parasites and infections Lethal P. Histological examination and measurement of parameters of liver injury Livers and blood were obtained from uninfected pregnant and non-pregnant mice, and IM pregnant and non-pregnant mice infected with P.

Comparative proteomic analysis Livers were obtained from uninfected pregnant and non-pregnant mice, and IM pregnant and non-pregnant mice infected with P. Enzyme-linked immunosorbent assay ELISA of cytokines An ELISA for the detection of IFN-γ or IL in plasma was carried out as described previously [ 18 ].

Results Proteomic analysis of the liver of immunized pregnant mice infected with P. Full size image. Table 1 Upregulated proteins in the liver of immunized pregnant mice infected with P. berghei NK65 Full size table.

Table 2 Downregulated proteins in the liver of immunized pregnant mice infected with P. Table 3 Protein levels in the livers of immunized pregnant inducible nitric oxide synthase-knockout iNOS-KO mice infected with P.

Table 4 Upregulated proteins in the livers of immunized pregnant inducible nitric oxide synthase-knockout iNOS-KO mice infected with P. Discussion Pregnant women infected with malaria parasites develop liver disease [ 8 , 9 , 10 ], but its pathogenesis remains unclear.

Conclusions iNOS plays a causative role in the development of liver disease during malaria in pregnancy. Availability of data and materials All data generated or analysed during this study are included in this published article and its additional files.

Abbreviations AFLP: Acute fatty liver of pregnancy ALT: Alanine aminotransferase AST: Aspartic aminotransferase HELLP: Hemolytic anemia; elevated liver enzymes; low platelet count iNOS: Inducible nitric oxide synthase LCHAD: Long-chain 3-hydroxyacyl CoA dehydrogenase NAFLD: Non-alcoholic fatty liver disease PSMs: Peptide spectral matches.

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Thank you for visiting nature. Hsalth are using a browser version with limited Nitrid for Nitric oxide and liver health. Healthh obtain the best ans, we recommend you use Muscle definition techniques more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. This study clarified the role of Cygb, the fourth globin in mammals originally discovered in rat hepatic stellate cells HSCsin cholestatic liver disease.