Introduction: 

Oxidative stress is related to the liver fibrosis. Hepatic stellate cells (HSC) play a key role in the pathogenesis of hepatic fibrosis by producing extracellular matrix proteins (ECM). The activation and the progression of activation of HSC depends on oxidative stress. It appears that oxidant stress anticipates HSC activation, being potential candidate for non-invasive quantification of fibrosis progression. Our aim was to correlate oxidative stress markers with the histological liver alterations in order to identify predictive, non-invasive parameters of fibrosis progression in toxic hepatitis evolution.

Material and Methods: 

The 50 animals (male Wistar rats, weight 200±10 gr) were randomly and equally divided into five experimental groups. In the four test groups, CCL₄ was administered intragastrically twice a week (1.2 ml/kg, CCL4 25% in sunflower oil). Control group received sunflower oil, same dose and way of administration. After 2, 3, 4 and 8 weeks of treatment, plasma levels of malondialdehyde (MDA), carbonylate proteins (CP), hydrogen donor ability (HD), sulfhydryl groups (SH), gluthation (GSH) and nitric oxide (NO) were measured, as well as the histological examination of the liver slices. Non-parametric Mann-Whitey U Test as well as receiver operating characteristic analysis with areas under curve (AUROC) determinations was used.

Results: 

Dynamic of histological disorders was assessed by the Knodell score (inflammation grade, fibrosis stage). Significant elevation of inflammation grade after only 2 weeks of experiment were obtained (p=0.001), while fibrosis alterations started to become significant (p=0.001) at 1 month of CCl4 administration. A good correlation between plasma MDA and liver fibrosis development was obtained (r=0.877, p= 0.050).

Correlation between CP dynamics and liver alterations was marginally significant for inflammation grade(r=0.756, p=0.138). HD evolution revealed a decreasing trend. A marginally inverse correlation with inflammation grade was obtained for HD (r=-0.794, 0.108). However, no correlation with liver fibrosis development could be established(r=-0.187, p=0.762). No correlations could be established for the others parameters with either inflammation grade or fibrosis stage.

Conclusions:

Our study shows that MDA elevation offers the best prediction potential for fibrosis, while marginal prediction fiability could be attributed to high levels of plasma CP and low levels of HD.

Keywords: 

oxidative stress, non-invasive markers, toxic hepatitis, fibrosis