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To Cite This Article: Parween Abdulsamad Ismail, Evaluation of Serum Nitric Oxide Levels and Some Biochemical Parameters in Patients with Liver Cirrhosis



liver cirrhosis occurs as a result of necrosis cells followed by fibrosis and formation of nodule, it is associated with changes in various biochemical parameters and various clinical manifestations in the patients. The objective of the current study to assessment the level of nitric oxide and some biochemical parameters in patients with liver Cirrhosis disease.
Evaluation of Serum Nitric Oxide Levels and Some
Biochemical Parameters in Patients with
Liver Cirrhosis
Hemn Jameel Majeed, Parween Abdulsamad Ismail* and Lutfia Muhammad Hassan
Department of Chemistry, University of Salahaddin, Iraq
*Corresponding author: Parween Abdulsamad Ismail, Department of Chemistry, College of Education, University of Salahaddin, Erbil,
To Cite This Article: Parween Abdulsamad Ismail, Evaluation of Serum Nitric Oxide Levels and Some Biochemical Parameters in Patients
with Liver Cirrhosis. 2020 - 8(1). AJBSR.MS.ID.001227. DOI: 10.34297/AJBSR.2020.08.001227.
Received: March 03, 2020; Published: March 10, 2020
Copy Right@ Parween Abdulsamad Ismail
This work is licensed under Creative Commons Attribution 4.0 License
American Journal of
Biomedical Science & Research
ISSN: 2642-1747
Research Article
Background:    
changes in various biochemical parameters and various clinical manifestations in the patients. The objective of the current study to assessment the
level of nitric oxide and some biochemical parameters in patients with liver Cirrhosis disease.
Methods: A total of 37 cases diagnosed clinically and biochemically as Cirrhosis disease and 35 age-matched controls were enrolled in the study.
Biochemical analyses were carried out which included estimation the level of serum Nitric oxide, albumin, Aspartate Transaminase (AST), Alanine
Results:                     
patients in comparison with control group.
Keywords: Liver Cirrhosis, Nitric Oxide, Liver Enzymes, Chronic Liver Diseases, Portal Hypertension, Cirrhotic Cardiomyopathy, Pulmonary Vascular
Abnormalities, Serum Enzymes, Chronic Active Hepatitis, Arteriovenous Inosculation
Chronic liver diseases may possibly classify into liver cirrhosis
and chronic active hepatitis. Liver illnesses it could be attended by
portal hypertension. Several systemic changes may occur with liver
cirrhosis and portal hypertension [1]. These abnormalities changes
  
      
syndrome, etc.). Furthermore, Liver cirrhosis is related to many
cardiovascular irregularities such us cirrhotic cardiomyopathy, and
pulmonary vascular abnormalities [2,3]. With the progression of
       
        
systems [4]. In addition, with the cirrhotic apparent, the cardiac
mitochondrial functions reduce in breathing regulator ratio and
Nitric Oxide (NO) is one of the most abundant products induced
with the catabolism of L-arginine in various mammalian cells, by the
action of enzymes that catalyze and regulate synthesis and catabolize
arginine. These induced and in certain alterations in the nitric oxide
synthase play main role in metabolic outcome of arginine in health
and disease subject [6,7]. In the beginning, the alteration of cell NO
releases was established mostly in the cardiovascular system, but
nowadays the ultimate role and twin effects (low concentration and
high concentration) had been recognized in various organizations
of human body [8]. The objective of the recent study was purposed
to determine the serum levels of Nitric Oxide in patient whom
American Journal of Biomedical Science & Research
Am J Biomed Sci & Res Copy@ Parween Abdulsamad Ismail
suffering with the liver cirrhosis and to exhibit their correlation
with the extra considerations such us serum albumin level and
Materials and Methods
Study Subjects
A total of thirty-seven cases which were diagnosed clinically
       
subjects were participated in the study. Their ages ranged from 36-
62 years. A total of thirty-seven serum samples were obtained from
individuals diagnosed with Liver Cirrhosis. Their ages ranged from
36-62 years.
Collection of Blood Samples
Approximately 5ml of venous blood was collected from
individuals. After coagulation, all samples were centrifuged at
3000rpm for 10 minutes and sera were stored at -70°C until
Biochemical Analysis
Assay of Nitric oxide concentration
Nitric oxide concentration has been estimated by using
sandwich enzyme immunoassay (ELISA) technique (BIOSOURCE,
Europe S.A., Belgium, Lot No.051501/B; 060601).
Principle of Human Nitric Oxide (NO) ELISA kit
This experiment was used double-sandwich ELISA technique
and the ELISA Kit provided was typical. The pre-coated antibody
was human NO monoclonal antibody and the detecting antibody
was polyclonal antibody with biotin labeled. Samples and biotin
labeling antibody were added into ELISA plate wells and washed
out with PBS or TBS. Then Avidin-peroxidase conjugates were
added to ELISA wells in order; Use TMB substrate for coloring after
reactant thoroughly washed out by PBS or TBS. TMB turns into
action of acid. The color depth and the testing factors in samples
were positively correlated.
Assay of Liver enzymes activities
      
     
        
Statistical Analysis of Data
Results are expressed as mean ± SD. Statistical comparisons
The results are illustrated in Table 1 and Figure 1. The mean serum
NO in liver cirrhosis, and control subjects were 90.34±8.45mmol/L
and 45.01±4.27mmol/L, respectively. Statistical evaluation showed
that nitric oxide levels were elevated in case groups compared
     
     
      
     
with liver cirrhosis as compared to control samples.
of liver mechanism process which causes the conversion from
prolonged liver disease to cirrhosis. These changes typically happen
         
septa with following parenchymal cell elimination and collapse of
hepatic vascular construction [9]. In addition, the disturbances of
the hepatic architecture produced by cirrhotic process increase the
   
issue is foremost to portal hypertension. Portal hypertension is a
most abundant and terrible obstacle of people suffering chronic
liver illness [10]. The pathological condition resulting from a portal
hypertension which has happened in consequence of destruction
to the portal veins is splanchnic overcrowding and opening of
ascites, splenomegaly etc.
Furthermore, concerning splanchnic arteriolar vasodilatation
which will causes portal hypertension facilitated by NO and act
        
retention due to stimulating antidiuretic hormone [2]. Our study
showed increased serum concentration of Nitric Oxide in patients
with cirrhosis. Several investigators also demonstrated that serum
NO concentrations are increased in hepatic cirrhosis [11-13].
The best explanation for increasing the NO concentrations is that
      
differences in serum nitrite and nitrate levels The initial cause of
         
venous hypertension, which increases shear stress and up-regulates
endothelial nitric oxide synthase, no doubt involved to nitric oxide
overproduction [14,15]. The anatomic sites of the enhanced NO
synthesis and release remain unclear. Evidence suggests that the
activity of NO synthase activity may be upregulated at different
sites, including the jejunum, gastric mucosa, and esophageal
mucosa [16-19].
The levels of nitric oxide are higher in portal venous plasma
than in peripheral venous plasma in patients with cirrhosis,
suggesting elevated splanchnic production of nitric oxide [12]. The
Am J Biomed Sci & Res Copy@ Parween Abdulsamad Ismail
American Journal of Biomedical Science & Research
activity of nitric oxide synthase in polymorphonuclear cells and
monocytes was elevated in patients who had cirrhosis. These cells
that provides evidence that this type of the enzyme may have a
role in peripheral vasodilatation in patients with cirrhosis [19].
Nitric Oxide which has been recognized as the utmost important
vasodilator of hepatic vascular nature regulation is formed by
endothelial cells. It is generally formed from the metabolism of
guanidine group of arginine [20,2]. In the recent study, our results
          
cirrhotic group than in the control group (Figure 1).
Figure 1: Mean values of serum NO in control and patients with liver Cirrhosis groups.
The various studies all agreed that serum NO concentrations
are raised in liver cirrhosis [1,2,5]. Despite the anatomic and the
mechanisms of the enhanced NO releases during cirrhosis is
 
that at different sites, such as esophageal mucosa, gastric mucosa,
and jejunum, NO synthase activity can be uncontrolled, and the
activity of erythrocyte adversely related with the serum level of
NO in liver cirrhotic patients [21]. The activity of serum ADA is
       
compared to normal healthy individuals in all age groups. The data
are in line with earlier results respectively [22,23]. The diagnosis
of organ disease is aided by estimation of several non-functional
plasma enzymes characteristic of that tissue or organ. The quantity
of enzymes produced depends on the degree of cellular damage,
the concentrations of the intracellular enzymes and the mass of
affected tissue.
The cause of the damage (viral infection, hypoxia, surgical,
chemical, or mechanical trauma) has no bearing on the enzymes
released into blood circulation. The levels of the enzymes released
yield mitochondrial enzymes as well. The use of appropriate
normal ranges is important in assessing abnormal levels of plasma
enzymes. Concerning liver injury, not liver normally functions are
referred to measurements each of the Aspartate Aminotransferase
   
(ALP). These laboratory measurement parameters are extremely
reproducible. Therefore, hepatic cirrhosis as a last stage of liver
disease or hepatic illnesses is required to assess and potential
evaluation of AST, ALT and ALP.
        
or ALP fractionation may trust an elevated ALP level of hepatic
origin. Despite, AST is elevated in the liver dysfunctions, but it
        
damage, because it is present in other organs rather than liver
      
       
ALT and AST in hepatic cirrhosis patients as compared to control
   
injury in both intra and extra hepatic failure, due to it is existence
   
of liver disease such as viral hepatitis, cholestasis and alcoholic
upper than normal values [25]. However, in our study persistence
as an indicator of cirrhosis.
Table 1: (Mean ± SD) of Biochemical parameters in liver cirrhotic patients and control group.
Parameters Control Patients P-value
Albumin(gm/dl) 4.8±0.68 2.43±0.47 
 63±11.67 187±35.09 
American Journal of Biomedical Science & Research
Am J Biomed Sci & Res Copy@ Parween Abdulsamad Ismail
ADA(IU/L) 15.07±1.92 48.01±6.40 
ALP(IU/L) 274±18.50 340±25.01 
ALT(IUL) 30.5±7.22 70.02±27.35 
AST(IUL) 27.91±5.71 80±27.12 
and ALP considered as a feature diagnostic of hepatic diseases,
subsequently enzymes are secreted into the bloodstream after the
worsening of the liver organ. Despite releasing these mitochondri-
and lipoproteins are used to estimate the status of liver function,
while an elevation of transaminase enzyme more than two times
totoxicity [26]. In this study, all the ADA, ALP and alanine trans-
aminase as well as aspartate transaminase enzymes raised from
(15.07±1.92, 274±18.50, 30.5±7.22 & 27.91±5.71) to (48.01±6.40,
340±25.01, 70.02±27.35 and 80±27.12) respectively.
Albumin is a family of spherical proteins produced in the liver
and is closely attendant with the systems of pathophysiology in
different forms of liver disease. Therefore, it has an important role
          
the current study shows considerably decrease concentration
of serum albumin in patient group (Table 1). This could cause by
the changing qualitatively in albumin structure and not purely a
quantitative decrease which is responsible for the defeat of it is
 
      
in liver disease. Albumin, bilirubin, and time of prothrombin
       
Increased levels of nitric oxide contributed to the hemodynamic
changes occur in patients of liver cirrhosis. Indicate that nitric oxide
has a pathophysiological role in liver cirrhosis.
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Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation, cirrhotic cardiomyopathy, and pulmonary vascular abnormalities. The pathogenic mechanisms of these cardiovascular changes are multifactorial and include neurohumoral and vascular dysregulations. Accumulating evidence suggests that cirrhosis-related cardiovascular abnormalities play a major role in the pathogenesis of multiple life-threatening complications including hepatorenal syndrome, ascites, spontaneous bacterial peritonitis, gastroesophageal varices, and hepatopulmonary syndrome. Treatment targeting the circulatory dysfunction in these patients may improve the short-term prognosis while awaiting liver transplantation. Careful fluid management in the immediate post-transplant period is extremely important to avoid cardiac-related complications. Liver transplantation results in correction of portal hypertension and reversal of all the pathophysiological mechanisms that lead to the cardiovascular abnormalities, resulting in restoration of a normal circulation. The following is a review of the pathogenesis and clinical implications of the cardiovascular changes in cirrhosis.
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Clinicians are required to assess abnormal liver chemistries on a daily basis. The most common liver chemistries ordered are serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin. These tests should be termed liver chemistries or liver tests. Hepatocellular injury is defined as disproportionate elevation of AST and ALT levels compared with alkaline phosphatase levels. Cholestatic injury is defined as disproportionate elevation of alkaline phosphatase level as compared with AST and ALT levels. The majority of bilirubin circulates as unconjugated bilirubin and an elevated conjugated bilirubin implies hepatocellular disease or cholestasis. Multiple studies have demonstrated that the presence of an elevated ALT has been associated with increased liver-related mortality. A true healthy normal ALT level ranges from 29 to 33 IU/l for males, 19 to 25 IU/l for females and levels above this should be assessed. The degree of elevation of ALT and or AST in the clinical setting helps guide the evaluation. The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson’s disease, and alpha-1 antitrypsin deficiency. In addition, a history of prescribed and over-the-counter medicines should be sought. For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken. Total bilirubin elevation can occur in either cholestatic or hepatocellular diseases. Elevated total serum bilirubin levels should be fractionated to direct and indirect bilirubin fractions and an elevated serum conjugated bilirubin implies hepatocellular disease or biliary obstruction in most settings. A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible.