scholarly journals Metabolomic analysis of diverse mice reveals hepatic arginase-1 as source of plasma arginase in Plasmodium chabaudi infection

2021 ◽  
Author(s):  
Nicole M Davis ◽  
Michelle M Lissner ◽  
Liliana M Massis ◽  
Crystal Lynette Richards ◽  
Victoria Chevée ◽  
...  
Keyword(s):  
Liver Damage ◽  
Phenotypic Diversity ◽  
Primary Source ◽  
Mouse Strains ◽  
Plasmodium Chabaudi ◽  
Human Malaria ◽  
Arginase 1 ◽  
Plasma Arginine ◽  
Mice Liver ◽  
Host Metabolism

Infections disrupt host metabolism, but the factors that dictate the nature and magnitude of metabolic change are incompletely characterized. To determine how host metabolism changes in relation to disease severity in murine malaria, we performed plasma metabolomics on eight Plasmodium chabaudi-infected mouse strains with diverse disease phenotypes. We identified plasma metabolic biomarkers for both the nature and severity of different malarial pathologies. A subset of metabolic changes, including plasma arginine depletion, match the plasma metabolomes of human malaria patients, suggesting new connections between pathology and metabolism in human malaria. In our malarial mice, liver damage, which releases hepatic arginase-1 (Arg1) into circulation, correlated with plasma arginine depletion. We confirmed that hepatic Arg1 was the primary source of increased plasma arginase activity in our model, which motivates further investigation of liver damage in human malaria patients. More broadly, our approach shows how leveraging phenotypic diversity can identify and validate relationships between metabolism and the pathophysiology of infectious disease.

Liver preneoplastic changes in mice treated with the herbicide fomesafen

1999 ◽  
Vol 18 (5) ◽  
pp. 338-344 ◽  
Author(s):  
J Krijt ◽  
P Stránská ◽  
J Sanitraák ◽  
A Chlumská ◽  
F Fakan
Keyword(s):  
Single Dose ◽  
Single Injection ◽  
Diphenyl Ether ◽  
Liver Histology ◽  
Mouse Strains ◽  
Toxicological Evaluation ◽  
Liver Nodules ◽  
Icr Mice ◽  
Mice Liver ◽  
Foci Of Altered Hepatocytes

1 Effect of the diphenyl ether herbicide fomesafen on liver preneoplastic changes and porphyrin biosynthesis was examined in male C57BL/6J mice (0.23% in the diet for 14 months) and ICR mice (0.3% in the diet for 50 weeks). Fomesafen treatment resulted in preneoplastic changes (liver nodules and foci of altered hepatocytes) in both strains, uroporphyria developed only in ICR mice. 2 Iron pretreatment (600 mg/kg as a single dose) accelerated the development of fomesafen-induced preneoplastic changes in both mouse strains. The number of foci containing altered hepatocytes, as well as the number and size of liver nodules, were increased in iron-pretreated animals. 3 A single injection of iron induced marked uroporphyria in C57BL/6J mice after 14 months (liver porphyrin content 102 nmol/g). This uroporphyria was further potentiated by fomesafen administration (208 nmol/g). 4 In ICR mice, liver histology was apparently normal after a 3 month recovery from fomesafen treatment (0.32% for 9 months). Liver porphyrin content (260 nmol/g) started to decrease immediately after fomesafen withdrawal, but was still significantly elevated after 3 months (5 nmol/g), as compared to controls (1 nmol/g). 5 It is concluded that the toxicological evaluation of fomesafen should focus on liver porphyrin biosynthesis.

scholarly journals MoG+: a database of genomic variations across three mouse subspecies for biomedical research

2021 ◽  
Author(s):  
Toyoyuki Takada ◽  
Kentaro Fukuta ◽  
Daiki Usuda ◽  
Tatsuya Kushida ◽  
Shinji Kondo ◽  
...  
Keyword(s):  
Phenotypic Diversity ◽  
Laboratory Mouse ◽  
Genomic Analysis ◽  
Inbred Strains ◽  
Genetic Distances ◽  
Mouse Strains ◽  
Comparative Genomic ◽  
Genome Database ◽  
Data Resource ◽  
Genomic Variations

AbstractLaboratory mouse strains have mosaic genomes derived from at least three major subspecies that are distributed in Eurasia. Here, we describe genomic variations in ten inbred strains: Mus musculus musculus-derived BLG2/Ms, NJL/Ms, CHD/Ms, SWN/Ms, and KJR/Ms; M. m. domesticus-derived PGN2/Ms and BFM/Ms; M. m. castaneus-derived HMI/Ms; and JF1/Ms and MSM/Ms, which were derived from a hybrid between M. m. musculus and M. m. castaneus. These strains were established by Prof. Moriwaki in the 1980s and are collectively named the “Mishima Battery”. These strains show large phenotypic variations in body size and in many physiological traits. We resequenced the genomes of the Mishima Battery strains and performed a comparative genomic analysis with dbSNP data. More than 81 million nucleotide coordinates were identified as variant sites due to the large genetic distances among the mouse subspecies; 8,062,070 new SNP sites were detected in this study, and these may underlie the large phenotypic diversity observed in the Mishima Battery. The new information was collected in a reconstructed genome database, termed MoG+ that includes new application software and viewers. MoG+ intuitively visualizes nucleotide variants in genes and intergenic regions, and amino acid substitutions across the three mouse subspecies. We report statistical data from the resequencing and comparative genomic analyses and newly collected phenotype data of the Mishima Battery, and provide a brief description of the functions of MoG+, which provides a searchable and unique data resource of the numerous genomic variations across the three mouse subspecies. The data in MoG+ will be invaluable for research into phenotype-genotype links in diverse mouse strains.

Aspartic proteases from Plasmodium chabaudi: a rodent model for human malaria

Acta Tropica ◽  
2003 ◽  
Vol 89 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Tiago M Martins ◽  
Carlos Novo ◽  
Virgı́lio E do Rosário ◽  
Ana Domingos
Keyword(s):  
Rodent Model ◽  
Plasmodium Chabaudi ◽  
Aspartic Proteases ◽  
Human Malaria

An experimental model for fatal malaria due to TNF-α-dependent hepatic damage

Parasitology ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 683-690 ◽  
Author(s):  
E. SEIXAS ◽  
P. OLIVEIRA ◽  
J. F. MOURA NUNES ◽  
A. COUTINHO
Keyword(s):  
Experimental Model ◽  
Liver Damage ◽  
Hepatic Damage ◽  
Plasmodium Chabaudi ◽  
Antibody Neutralization ◽  
Tnf Α ◽  
Hepatocyte Death

SUMMARYWhile BALB/c mice survive infection with blood stages ofPlasmodium chabaudi chabaudi(AS), 70% of DBA/2 mice die by day 9–11 of infection, both strains controlling parasitaemia. We describe here that infection of DBA/2 mice results in extensive, multifocal hepatocyte death. Antibody neutralization of TNF-α prevents both liver damage and death.

scholarly journals C57BL/6 and A/J Mice Have Different Inflammatory Response and Liver Lipid Profile in Experimental Alcoholic Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Lorena Bavia ◽  
Íris Arantes de Castro ◽  
Lourdes Isaac
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Genetic Background ◽  
Inflammatory Responses ◽  
Liver Lipid ◽  
Liver Steatosis ◽  
Public Health Issue ◽  
Mouse Strains ◽  
Mice Liver

Alcoholic liver disease (ALD) is an important worldwide public health issue characterized by liver steatosis, inflammation, necrosis, and apoptosis of hepatocytes with eventual development of fibrosis and cirrhosis. Comparison of murine models with different inflammatory responses for ALD is important for an evaluation of the importance of genetic background in the interpretation of ethanol-induced phenotypes. Here, we investigated the role of inflammation and genetic background for the establishment of ALD using two different mouse strains: C57BL/6 (B6) and A/J. B6 and A/J mice were treated with a high fat diet containing ethanol (HFDE) and compared to the controls for 10 weeks. Hepatomegaly and steatohepatitis were similar in B6 and A/J mice, but only A/J mice were resistant to weight gain. On the other hand, HFDE-fed B6 accumulated more triglycerides (TG) and cholesterol and presented more intense cellular infiltrate in the liver when compared to HFDM-fed mice. Liver inflammatory environment was distinct in these two mouse strains. While HFDE-fed B6 produced more liver IL-12, A/J mice increased the TNF-αproduction. We concluded that mouse genetic background could dictate the intensity of the HFDE-induced liver injury.

scholarly journals PENGARUH PEMBERIAN TUAK TERHADAP GAMBARAN HISTOPATOLOGI HATI MENCIT (Mus musculus) ICR JANTAN

2020 ◽  
Vol 11 (2) ◽  
pp. 193
Author(s):  
St Aisyah Sijid ◽  
Cut Muthiadin ◽  
Zulkarnain Zulkarnain ◽  
Ar. Syarif Hidayat
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Liver Damage ◽  
Mus Musculus ◽  
Liver Weight ◽  
Palm Wine ◽  
Icr Mice ◽  
Liver Histopathology ◽  
Mice Liver ◽  
Different Doses

Liver damage or liver disease is caused by many factors, one of which is by consuming drinks that contain alcohol. Tuak is one of the drinks that contain alcohol. This study aims to determine the effect of palm wine administration on the histopathological picture of male ICR mice (Mus musculus) liver. This study used 20 mice consisting of 4 treatments namely P0 = 0 mL / day / head; P1 = 0.1 mL / day / head; P2 = 0.2 mL / day / head and P3 = 0.3 mL / day / head. The parameters observed were body weight of mice, liver weight and liver histopathology of mice. The results showed that administration of palm wine to male ICR mice at different doses gave an influence on the histopathological picture of male ICR mice (Mus musculus).AbstrakKerusakan hati atau penyakit liver disebabkan oleh banyak faktor, salah satunya adalah dengan mengkonsumsi minuman yang mengandung alkohol. Tuak merupakan salah satu minuman yang mengandung alkohol. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian tuak terhadap gambaran histopatologi hati mencit (Mus musculus) ICR jantan. Penelitian ini menggunakan 20 ekor mencit yang terdiri dari 4 perlakuan yaitu P0 = 0 mL/hari/ekor; P1 = 0,1 mL/hari/ekor; P2 = 0,2 mL/hari/ekor dan P3 = 0,3 mL/hari/ekor. Parameter yang diamati adalah berat badan mencit, berat hati dan histopatologi hati mencit. Hasil penelitian menunjukkan bahwa pemberian tuak pada mencit ICR jantan dengan dosis yang berbeda memberikan pengaruh terhadap gambaran histopatologi hati mencit (Mus musculus) ICR jantan.Kata Kunci: Hati, Histopatologi, Mencit, Tuak

Production of arginine by the kidney is impaired in a model of sepsis: early events following LPS

2004 ◽  
Vol 287 (6) ◽  
pp. R1434-R1440 ◽  
Author(s):  
Mark J. Lortie ◽  
Joseph Satriano ◽  
Francis B. Gabbai ◽  
Sonia Thareau ◽  
Ser Khang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Time Course ◽  
Primary Source ◽  
Renal Perfusion ◽  
Inos Expression ◽  
Inos Activity ◽  
Human Sepsis ◽  
Arterial Blood ◽  
Plasma Arginine ◽  
Oxide Synthase

Lipopolysaccharide (LPS) is used experimentally to elicit the innate physiological responses observed in human sepsis. We have previously shown that LPS causes depletion of plasma arginine before inducible nitric oxide synthase (iNOS) activity, indicating that changes in arginine uptake and/or production rather than enhanced consumption are responsible. Because the kidney is the primary source of circulating arginine and renal failure is a hallmark of septicemia, we determined the time course of changes in arginine metabolism and kidney function relative to iNOS expression. LPS given intravenously to anesthetized rats caused a decrease in mean arterial blood pressure after 120 min that coincided with increased plasma nitric oxide end products (NOx) and iNOS expression in lung and liver. Interestingly, impairment of renal function preceded iNOS activity by 30–60 min and occurred in tandem with decreased renal arginine production. The baseline rate of renal arginine production was ∼60 μmol·h−1·kg−1, corresponding to an apparent plasma half-life of ∼20 min, and decreased by one-half within 60 min of LPS. Calculations based on the systemic production and clearance show that normally only 5% of kidney arginine output is destined to become nitric oxide and that <25% of LPS-impaired renal production was converted to NOx in the first 4 h. In addition, we provide novel observations indicating that the kidney appears refractory to iNOS induction by LPS because no discernible enhancement of renal NOx production occurred within 4 h, and iNOS expression in the kidney was muted compared with that in liver or lung. These studies demonstrate that the major factor responsible for the rapid decrease in extracellular arginine content following LPS is impaired production by the kidney, a phenomenon that appears linked to reduced renal perfusion.

scholarly journals Genetic control of susceptibility to infection with Plasmodium chabaudi chabaudi AS in inbred mouse strains

2011 ◽  
Vol 13 (2) ◽  
pp. 155-163 ◽  
Author(s):  
A Laroque ◽  
G Min-Oo ◽  
M Tam ◽  
I Radovanovic ◽  
M M Stevenson ◽  
...  
Keyword(s):  
Genetic Control ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Plasmodium Chabaudi ◽  
Susceptibility To Infection

scholarly journals The effect of apple (Malus Domestica) juice on the damage of mice liver cells due to paracetamol treatment

2009 ◽  
Vol 21 (2) ◽  
Author(s):  
Anthony Hartanto ◽  
Murnisari Dardjan ◽  
Silvi Kintawati
Keyword(s):  
Liver Damage ◽  
Malus Domestica ◽  
Apple Juice ◽  
Liver Cells ◽  
High Dose ◽  
Toxic Agent ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Mice Liver

The liver is an important organ for body metabolism process. Liver disease is one of serious health problems in developing countries including Indonesia. Liver damage is caused by viral infection, toxic agent exposure (medications, alcohol), hormonal disturbance, neoplasm and autoimmune diseases. The use of high dose paracetamol to reduce pain also leads to liver damage. Apple (Malus domestica) juice is a natural anti oxidant agent. This laboratory experimental study was performed to discover the effect of giving apple juice on damaged cell regeneration due to the use of paracetamol. The study was performed in 21 male mice from Swiss-Webster strain that were divided into group I, II, and III. Group, I served as control while group II received 1 mg/ml paracetamol dose for 5 days and Group III received 1 mg/ml paracetamol for 5 days and 1 ml of apple juice on the 5th to 10th day. The observation of the mice liver cells was conducted using a light microscope with 400x magnification to get the number of necrotic liver cells per view field. The results of this study showed a difference in the number of necrotic liver cells between Group II and III. ANOVA statistical test ( = 0.05) concluded that apple juice significantly helps regeneration process in damaged liver cells caused by paracetamol.

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