الفهرس 
Non Alcoholic SteatohepatitisOnly 14 pages are availabe for public view
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Abstract
An increasing body of literature suggests a connection between NASH and insulin resistance. It is increasingly recognized that diabetic patients are more prone to develop NASH. The severity of NASH was also found to be greater among diabetic patients.
Multiple studies also revealed that NASH patients were more likely to develop cardiovascular complications. Indeed, NASH has been reported in several studies to contribute to enhanced risk for atherosclerosis. A possible explanation for the association of NASH, insulin resistance and atherosclerosis may be the fact that all these disorders share a common underlying pathology which is inflammation. TNF-α is an inflammatory mediator secreted by several inflammatory cell types. In fact, TNF-α appear to play a pathophysiological role in different conditions, such as NASH, atherosclerosis and insulin resistance.
Depression is one of newly recognized association with NASH. Indeed, depression is also associated with insulin resistance and inflammatory states, factors that are relevant to the development of NASH.
Recently, bupropion, an atypical antidepressant, has been found to have anti-inflammatory effect, most likely through TNF-suppression.
The recent growing interest involving the pathophysiological link between NASH, depression and role of TNF-α magnify the importance to study the effect of anti-depressant drugs on NASH progression.
Aim of the study
Is to investigate the potential role of anti-inflammatory effect of bupropion on some biochemical, cardiovascular and hepatic histopathological changes in a model of NASH and insulin resistance induced by HFD.
Study design
The first preliminary part of the study was done on 18 rats to establish the full picture of NASH model, animals were fed high fat diet and were sacrificed 8, 12 and 15 weeks after feeding (6 rats for each time point), for evaluation of liver histopathology.
Then the second part of the study was done on 30 animals divided into three groups: control (chow fed group) (n=10), NASH untreated group (HFD fed group for 15 weeks) (n=10) and bupropion treated group (HFD fed for 15 weeks then were treated with bupropion 50mg/kg/day orally for 4 weeks).
The rats in all tested groups were assessed for:
I. Biochemical parameters
(A) Intraperitoneal glucose tolerance test.
(B)Insulin resistance and fasting insulin level
(C)Lipid profile
a. Serum free fatty acids
b. Serum total cholesterol
c. Serum triglycerides
(D) Hepatic TNF α concentration
(E)Serum ALT
II. CVS parameters
(A) Systolic blood pressure measurement
(B) Electrocardiograph (ECG) recording
(C) Isolated aortic reactivity to phenylepherine and acetylcholine
(D) Aortic intima /media ratio.
III. Liver index
IV. Histopathological changes in liver
Liver tissue was stained with H&E to determine grading of steatosis, lobular inflammatory infiltration and hepatocytes ballooning
The results could be summerized as follow:
(A) Effect of HFD on some biochemical, cardiovascular and hepatic histopathological parameters.
HFD for 15 weeks produced statistically significant impairment of glucose tolerance, insulin resistance and dyslipidemia (increased serum total cholesterol, free fatty acids and triglycerides) associated with increased aortic intima/media ratio with subsequent endothelial dysfunction which was manifested by increase in the contractile response to phenylepherine (decrease in EC50 and increase in Emax) and decrease in the relaxant response to acetylcholine. Additionally, HFD for 15 weeks produced statistically significant elevation in systolic blood pressure. While, there was non significant change in ECG parameters. It also produced a statistically significant increase in liver index, hepatic TNF-α concentration and liver enzyme (ALT) together with hepatic steatosis and necroinflammatory lesions indicative of complete pathological features of NASH.
(B) Effect of Bupropion on NASH
Bupropion treatment (50mg/kg/day) orally for 4 weeks produced a statistically significant improvement in glucose tolerance, insulin resistance, dyslipidemia (serum triglycerides and FFAS), hepatic TNF-α concentration, hepatic histopathological changes and the elevated systolic blood pressure in NASH model as compared to NASH untreated group. It failed to produce statistically significant improvement in ECG parameters, serum total cholesterol, endothelial dysfunction as well as the increased aortic intima/media ratio as compared to NASH untreated group.
Bupropion which was approved as antidepressant plays a role in NASH model in rats as an anti TNF-α (anti-inflammatory effect) due to it´s improvement of some features associated with NASH model such as hepatic histopathological changes, insulin resistance, hypertriglyceridemia, elevated FFAs, elevated hepatic TNF-α concentration and elevated systolic blood pressure.
So, bupropion may be benifecial in patients complaining of depression with steatohepatitis and metabolic disorders. This study awaits further investigations to be established.