Serum thioredoxin as an indicator of iron-induced oxidative stress in chronic viral hepatitis

Abstract

Aim: Thioredoxin (TRX), a thiol-containing protein, is induced by various oxidative stresses. The aim of the present study is to evaluate the clinical significance of serum TRX levels in patients with chronic viral hepatitis. Methods: TRX levels and other laboratory parameters, including ironmarkers, were measured in the sera of patients with chronic hepatitis type C (CH-C, n= 163) and type B (CH-B, n=35) as well as in healthy controls (n=17). Forty-five of the CH-C patients underwent a liver biopsy. Fifteen of the CH-C patients received biweekly phlebotomies in which 400 ml of blood were drawn. Serum TRX levels were determined using a recently established sandwich ELISA kit (Fujirebio Inc., Japan). Results: I) Serum TRX levels (ng/ml, mean:tSD) were significantly higher in CH-C patients (39.1±21.2) than in CH-B patients (30.9± 16.5)(p<.05) or in controls (20.6± 12.5)(p<.001). No significant differences in TRX levels were found between CH-B patients and controls. 2) TRX levels did not correlate with ALT levels or virus titers in either CH-C or CH-B patients. Serum iron, ferritin, and transferrin saturation values were significantly higher in the CH-C patients than in the CH-B patients (p<.05). Serum TRX levels were significantly correlated with these iron-markers in CH-C patients, but not in CH-B patients. 3) In CH-C patients, significant correlations were observed between TRX levels and the levels of serum markers for hepatic fibrosis, such as hyaluronic acid, IV collagen, and P-III-P. Histological examination also demonstrated that TRX levels were significantly correlated with the degree of hepatic fibrosis (r=0.333, p<.05), but not with that of hepatic activity. Serum ferritin levels tended to increase with the progression of fibrosis. 4) The removal of excess iron by phlebotomy resulted in a reduction of TRX and ferritin serum levels in CH-C patients. Conclusions: The present findings suggest that serum TRX levels may be a useful indicator of oxidative stress in hepatitis patients. The positive correlations between serum TRX levels and the value of iron-markers as well as the histological stages of hepatic fibrosis and the good response of CH-C patients to phlebotomy indicate that iron-induced oxidative stress may contribute to the pathological mechanism of hepatitis C. No significant increases in serum TRX levels were found in CH-B patients, suggesting that hepatitis B may not be influenced by oxidative stress.