Circadian Rhythm of Plasma Lipid Peroxidation and Total Antioxidant Status in Patients with Alcoholic Hepatitis: A Comparative Cross-Sectional Study

Abstract

Background: Oxidative stress is central to the pathogenesis of alcoholic liver disease, and both the generation of reactive oxygen species and antioxidant capacity are under circadian control. Most clinical studies, however, have measured oxidative-stress markers at a single time of day. This study characterised the twenty-four-hour profile of plasma malondialdehyde (MDA), a marker of lipid peroxidation, and of total antioxidant status (TAS), an integrated measure of antioxidant capacity, in patients with alcoholic hepatitis and in healthy controls.

Methods: In a cross-sectional comparative study with repeated measures over twenty-four hours, thirty patients with alcoholic hepatitis and thirty age- and sex-matched healthy controls were studied. Venous blood was sampled at 06:00, 12:00, 18:00 and 00:00 h. Plasma MDA was estimated by the thiobarbituric-acid method and TAS by a standardised assay. Between-group differences at each time were tested by Student’s t-test; circadian characteristics (MESOR, amplitude, acrophase) were derived by single-cosinor rhythmometry.

Results: A significant circadian rhythm of MDA was demonstrable in both groups. In patients the MDA MESOR was significantly higher (5.16 ± 0.71 versus 3.39 ± 0.38 nmol/ml; p < 0.001), the amplitude reduced (0.41 ± 0.12 versus 0.64 ± 0.15; p = 0.002) and the acrophase advanced from the late afternoon (≈16:21 h) towards midday (12.18 ± 1.5 versus 16.35 ± 1.2 h; p < 0.001). Plasma TAS was significantly lower in patients at every sampling time (all p < 0.001) and its diurnal variation was blunted.

Conclusion: Patients with alcoholic hepatitis show an elevated, phase-advanced and amplitude-attenuated rhythm of lipid peroxidation together with a persistently depressed total antioxidant status across the twenty-four-hour cycle, indicating that oxidative injury is both quantitatively increased and temporally dysregulated. As a cross-sectional study this work cannot establish causation; the findings are hypothesis-generating for the time-qualified interpretation of oxidative-stress markers and for future chronotherapeutic research.