Importance of cytokines, oxidative stress and expression of BCL-2 in the pathogenesis of non-alcoholic steatohepatitis.
OBJECTIVE
Non-alcoholic steatohepatitis (NASH) is a form of chronic hepatitis. The pathogenesis of NASH has been dealt with in only a few studies and so it has not been clearly identified yet. The purpose of this study was to investigate the roles of TNF-alpha, TGF-beta, IL-6, IL-8, malondialdehyde (MDA), nitric oxide (NO) and the expression of Bcl-2 and Bax in the pathogenesis of NASH.


METHODS
The study included 92 patients, 57 of whom were diagnosed with biopsy-proven NASH, 13 with biopsy-proven hepatosteatosis and 22 with ultrasonography-diagnosed hepatosteatosis. Serum levels of TNF-alpha, TGF-beta, IL-6 and IL-8 were measured using the ELISA method. The plasma levels of NO were studied using the Griess method. Expressions of Bcl-2 and Bax were examined in paraffin blocks of liver biopsy materials by means of immunohistochemical-staining. MDA levels were measured using the thiobarbituric acid method.


RESULTS
No significant difference was found in the levels of TNF-alpha, TGF-beta, IL-6 or NO between the three groups (p>0.05). No difference was found in expression of Bcl-2 and expression of Bax between the biopsy-proven NASH and biopsy-proven hepatosteatosis groups (p>0.05). In the NASH group, the levels of IL-8 and MDA were found to be higher than those in the hepatosteatosis groups (p<0.05).


CONCLUSIONS
The elevated levels of MDA may indicate the relationship between oxidative stress and NASH. Furthermore, IL-8 was found to be higher in the NASH group than in the hepatosteatosis group, demonstrating the importance of inflammation in the pathogenesis of NASH.
Torer
Nihan
N
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Gazi University Faculty of Medicine, Ankara, Turkey. nihan_torer@hotmail
Ozenirler
Seren
S
Yucel
Aysegul
A
Bukan
Neslihan
N
Erdem
Ozlem
O
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016207:Cytokines / Q000097:blood*; D005234:Fatty Liver / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008111:Liver Function Tests; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress; D011446:Prospective Studies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D051028:bcl-2-Associated X Protein / Q000032:analysis
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D019253:Proto-Oncogene Proteins c-bcl-2; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D008315:Malondialdehyde