scholarly journals Dimethylnitrosamine (DMN)-induced fibrotic rats: effect of Vernonia amygdalina on extracellular matrix and Hepatic/lysosomal integrity

2016 ◽  
Vol 4 (1) ◽  
pp. 7
Author(s):  
Usunomena Usunobun ◽  
Ngozi Okolie

<p><strong>Background:</strong> Hepatic fibrosis is the accumulation of extracellular matrix protein, or scar, in response to acute or chronic liver injury. This study investigated the effect of ethanolic leaf extract of <em>Vernonia amygdalina</em> on extracellular matrix protein: hyaluronic acid (HA), liver synthetic molecules: total protein (TP), albumin (ALB), total bilirubin (TB) as well as lysosomal membrane stability: acid phosphatase (ACP) in dimethylnitrosamine (DMN)-induced fibrotic rats.</p><p><strong>Methods:</strong> Wistar albino male rats were intraperitoneally injected with 10 mg/kg DMN on first three days a week for two weeks. Ethanolic leaf extracts of <em>Vernonia amygdalina</em> (200 mg /kg) was administered simultaneously by oral gavage daily for two weeks. All rats were sacrificed after 24 hours of last administration by cardiac puncture, and blood collected from the ocular vein. Analysis of serum ACP and LDH activities with those of the concentrations of HA, ALB, TP and TB were carried out.</p><p><strong>Results:</strong> Administration of DMN to rats significantly increased HA and TB concentration and the activities of ACP and LDH (p&lt;0.05) in the serum while it significantly reduced (p&lt;0.05) serum TP and ALB concentrations when compared with controls. However, simultaneous administration of ethanolic leaf extracts of <em>Vernonia amygdalina</em> with DMN significantly (p&lt;0.05) reversed these changes.</p><p><strong>Conclusion:</strong> This study shows that <em>Vernonia amygdalina</em> possesses hepatoprotective, lysosomal membrane stabilizing and anti-fibrotic properties may be due to its antioxidant and phytochemical constituents.</p>

2016 ◽  
Vol 4 (1) ◽  
pp. 10 ◽  
Author(s):  
Usunomena Usunobun ◽  
Ngozi Okolie

<p><strong>Background:</strong> Hepatic fibrosis is a pre-pathologic state of cirrhosis, which plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). This study was carried out to evaluate the hepatoprotective effect of <em>Annona muricata</em> leaves on extracellular matrix (ECM) accumulation, lysosomal membrane integrity and liver damage in dimethylnitrosamine (DMN)-induced fibrotic rats.</p><p><strong>Methods:</strong> Healthy adult male wistar rats were divided into four groups. Group I rats received normal saline and served as control, Group II rats were administered 200mg/kg <em>Annona muricata</em>, Group III received 200mg/kg <em>Annona muricata</em> orally simultaneously with 10mg/kg DMN, Group IV received 10 mg/kg DMN without extract. DMN administered intraperitoneally was on first three days of each week for two weeks while <em>Annona muricata</em> was administered for 14 consecutive days. 24 hours after last administration, all animals were sacrificed and blood collected for serum analysis. Biochemical parameters such as lactate dehydrogenase (LDH), total bilirubin (TB), total protein (TP), and albumin (ALB) were estimated to assess liver function and synthetic ability while hyaluronic acid (HA) was determined to assess extracellular matrix (ECM) function. In addition, acid phosphatase (ACP) was estimated to assess lysosomal membrane stability/fragility.</p><p><strong>Results:</strong> Liver damage, decreased synthetic ability, lysosomal membrane fragility and altered ECM function were evident by an increase in the levels of LDH, TB, ACP and HA as well as a decrease in level of TP and ALB in sera of rats administered DMN compared to normal rats. However, simultaneous treatment with <em>Annona muricata</em> leaf extract significantly (p&lt;0.05) reversed alterations in the above indices.</p><p><strong>Conclusion:</strong> This study suggests that <em>Annona muricata</em> leaf functions as a potent fibrosuppressant by suppressing ECM accumulation, enhancing lysosomal membrane stability and liver synthetic ability.</p>


2007 ◽  
Vol 177 (4S) ◽  
pp. 421-422
Author(s):  
Ganka Nikolova ◽  
Christian O. Twiss ◽  
Hane Lee ◽  
Nelson Stanley ◽  
Janet Sinsheimer ◽  
...  

Author(s):  
Aniel Moya-Torres ◽  
Monika Gupta ◽  
Fabian Heide ◽  
Natalie Krahn ◽  
Scott Legare ◽  
...  

Abstract The production of recombinant proteins for functional and biophysical studies, especially in the field of structural determination, still represents a challenge as high quality and quantities are needed to adequately perform experiments. This is in part solved by optimizing protein constructs and expression conditions to maximize the yields in regular flask expression systems. Still, work flow and effort can be substantial with no guarantee to obtain improvements. This study presents a combination of workflows that can be used to dramatically increase protein production and improve processing results, specifically for the extracellular matrix protein Netrin-1. This proteoglycan is an axon guidance cue which interacts with various receptors to initiate downstream signaling cascades affecting cell differentiation, proliferation, metabolism, and survival. We were able to produce large glycoprotein quantities in mammalian cells, which were engineered for protein overexpression and secretion into the media using the controlled environment provided by a hollow fiber bioreactor. Close monitoring of the internal bioreactor conditions allowed for stable production over an extended period of time. In addition to this, Netrin-1 concentrations were monitored in expression media through biolayer interferometry which allowed us to increase Netrin-1 media concentrations tenfold over our current flask systems while preserving excellent protein quality and in solution behavior. Our particular combination of genetic engineering, cell culture system, protein purification, and biophysical characterization permitted us to establish an efficient and continuous production of high-quality protein suitable for structural biology studies that can be translated to various biological systems. Key points • Hollow fiber bioreactor produces substantial yields of homogenous Netrin-1 • Biolayer interferometry allows target protein quantitation in expression media • High production yields in the bioreactor do not impair Netrin-1 proteoglycan quality Graphical abstract


2002 ◽  
Vol 267 (4) ◽  
pp. 440-446 ◽  
Author(s):  
A. Kapetanopoulos ◽  
F. Fresser ◽  
G. Millonig ◽  
Y. Shaul ◽  
G. Baier ◽  
...  

1997 ◽  
Vol 16 (5) ◽  
pp. 289-292 ◽  
Author(s):  
Maureen R. Johnson ◽  
Douglas J. Wilkin ◽  
Hans L. Vos ◽  
Rosa Isela Ortiz De Luna ◽  
Anindya M. Dehejia ◽  
...  

1989 ◽  
Author(s):  
Lyndon Su ◽  
Louann W. Murray ◽  
Rodney A. White ◽  
George Kopchok ◽  
Carol Guthrie ◽  
...  

2000 ◽  
Vol 275 (6) ◽  
pp. 3999-4006 ◽  
Author(s):  
Andreas R. Klatt ◽  
D. Patric Nitsche ◽  
Birgit Kobbe ◽  
Matthias Mörgelin ◽  
Mats Paulsson ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Meenalakshmi M. Mariappan

Renal hypertrophy and accumulation of extracellular matrix proteins are among cardinal manifestations of diabetic nephropathy. TGF beta system has been implicated in the pathogenesis of these manifestations. Among signaling pathways activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin-)regulated pathways are pivotal in orchestrating high glucose-induced production of ECM proteins leading to functional and structural changes in the kidney culminating in adverse outcomes. Understanding signaling pathways that influence individual matrix protein expression could lead to the development of new interventional strategies. This paper will highlight some of the diverse components of the signaling network stimulated by hyperglycemia with an emphasis on extracellular matrix protein metabolism in the kidney in diabetes.


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