Essential Role of Thioredoxin and Glutathione in Pancreas

Acute pancreatitis (AP) is defined by acute inflammatory injury to the pancreas and oxidative stress has been implicated as a mechanistic driver of disease progression. To delineate the contribution of reactive oxygen species (ROS) detoxification pathways in AP, we employed a genetic model of pancreas-specific deletion of the thioredoxin reductase 1 (Txnrd1) gene, either alone or in conjunction with pharmacological inhibition of glutathione synthesis via buthionine sulfoximine (BSO). AP was induced in these cohorts and in control animals. Pancreatic tissues were harvested at baseline (0 h), 8 h, 24 h, and 7 days post-induction for RNA sequencing to capture dynamic transcriptional programs. This experimental framework was designed to generate in vivo evidence on how modulation of ROS-scavenging systems influences pancreatic injury severity and subsequent repair processes in the context of AP.