Concurrent erythrocyte glutathione depletion and oxidative shift of the serum thiol–disulfide pool in acute pancreatitis: a case–control study

Oxidative stress is central to acute pancreatitis. Thiol groups drive antioxidant defense in both the extracellular serum thiol-disulfide system and the intracellular glutathione system, yet they have rarely been assessed together in this disease. In a prospective case-control study we enrolled 81 adults with acute pancreatitis and 74 emergency-department controls with non-specific abdominal pain. Serum native and total thiol were measured spectrophotometrically and erythrocyte reduced (GSH) and total glutathione by a colorimetric assay; dynamic disulfide, oxidized glutathione (GSSG), and the ratios were derived. Native thiol was the prespecified primary endpoint. Reduced glutathione (Cohen d = -2.32) and total glutathione (d = -1.83) were lower in patients, and the GSSG/GSH ratio was higher (rank-biserial r = 0.89; all p < 0.001). Native thiol, the primary endpoint, was also lower (d = -1.14; p < 0.001), as was total thiol (d = -0.78), whereas dynamic disulfide (d = 1.24) and the disulfide/total thiol ratio (d = 2.04) were higher. The differences persisted in patients without any comorbidity and within each sex. Severe disease showed moderately lower native and total thiol than mild disease (d = -0.78 and -0.69), but no severity comparison survived correction for multiple testing. Both thiol-based antioxidant compartments were therefore disturbed in acute pancreatitis: the erythrocyte glutathione pool was depleted and oxidized, and the serum thiol pool, most of which resides on albumin, was lower and shifted toward disulfide. The largest change was in the glutathione compartment, and only the serum markers showed a preliminary association with severity.