Detection of DNA damage in nonalcoholic steatohepatitis; and its correlation with serum imbalance of adiponectin/tumor necrosis factor-alpha

ABSTRACT

NASH is a potentially serious condition, since as many as 25% of patients with NASH may progress to cirrhosis and experience complications of portal hypertension, liver failure, and hepatocellular carcinoma. The aim of the present work is to study DNA damage in patients with NASH and correlate this damage with serum levels of adiponectin and TNF-alpha in those patients to evaluate their role in the pathogenesis of the disease. The study was carried out on 20 patients with NASH [8 males and 12 females] and 10 healthy age and sex matched individuals as a control group. Detection of DNA damage in liver tissues was performed by gel electrophoresis. Serum levels of adiponectin and TNF-alpha were estimated in all patients and control group. There was a statistically significant increase in DNA damage in NASH patients than control subjects, detected by the intensity of the damaged DNA bands expressed by maximum optical density [max. OD], where it was 36.57 +/- 18.60 in NASH group and 0.088 +/- 0.02 in control subjects [p<0.001]. The intensity of the damage and fragmentation of DNA was not the same in all patients with NASH. More damage was detected in subgroup A, the max. OD in this group was 66.834 +/- 7.21. There was significant decrease in serum adiponectin level and significant increase in serum TNF- a level in NASH patients than control subjects [5.69 +/- 1.49 micro g/ml versus 13.67 +/- 1.6 micro g/ml and 9.12 +/- 3.1 pico g/ml versus 2.7 +/- 1.4 pg/ml respectively]. TNF- a serum level in NASH patients had significant positive correlation with DNA damage in those patients [r = 0.46, p <0.001], while serum adiponectin level had negative correlation with DNA damage in NASH [r = - 0.63, p 0.001]. DNA damage occurs in NASH patients as a result of increased oxidative stress and altered cytokine metabolism in the form of increased TNF- alpha and decreased adiponectin levels. Measures to prevent oxidative stress or inhibit TNF-alpha or increase adiponectin may improve NASH