Vitamin B12 Attenuates Acute Pancreatitis by Suppressing Oxidative Stress and Improving Mitochondria Dysfunction via CBS/SIRT1 Pathway

Abstract

Acute pancreatitis is an inflammatory disorder of the pancreas associated with substantial morbidity and mortality, which is characterized by a rapid depletion of glutathione (GSH). Cysthionine-β-synthase (CBS) is a key coenzyme in GSH synthesis, and its deficiency is related to a variety of clinical diseases. However, whether CBS is involved in the pathogenesis of acute pancreatitis remains unclear. First, we found that CBS was downregulated in both in vivo and in vitro AP models. The pancreatic damage and acinar cell necrosis related to CBS deficiency were significantly improved by VB 12, which stimulated clearance of reactive oxygen species (ROS) by conserving GSH. Furthermore, EX-527 (a specific inhibitor of SIRT1) exposure counteracted the protective effect of VB 12 by promoting oxidative stress and aggravating mitochondrial damage without influencing CBS, indicating that vitamin B12 regulates SIRT1 to improve pancreatical damage by activating CBS. In conclusion, we found that VB 12 protected acute pancreatitis associated with oxidative stress via CBS/SIRT1 pathway.

Emerging Trends in Intestinal Knowledge Structure Associated With Acute Pancreatitis From 1981 to 2021

“…Current reports indicate that the pathogenesis and prognosis of AP might be associated with oxidative stress-related acinar cell necrosis, and antioxidation could reduce pancreatic necrosis. 49,50 Recent studies have shown that AP is associated with oxidative stress, and levels of oxidative stress markers are significantly related to the severity and prognosis of disease. 51 Some molecules could be used as early biomarkers of this disease in the future.…”

Thioredoxin-interacting protein deficiency protects against severe acute pancreatitis by suppressing apoptosis signal-regulating kinase 1

“…The local pancreatic activation of transcription factors, recruitment of inflammatory cells, and the production of inflammatory mediators such as TNF-α and IL-1β, further potentiate the local tissue destruction and increase the potential for a life-threatening systemic inflammatory response [ 9 , 10 ]. Oxidative stress also plays a major role in SAP, as evidenced by diminished reduced glutathione levels, elevated malondialdehyde (MDA) levels, and reduced superoxide dismutase (SOD) activity in the pancreas [ 11 ]. In addition to acting as deleterious agents, reactive oxygen species (ROS) are signal-transducing molecules that trigger proinflammatory cytokine production and induce persistent tissue damage in SAP [ 12 ].…”