Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2‐Mediated Oxidative Stress and NLRP3 Inflammatory Pathway

Abstract

Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP-associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes including quinoneoxidoreductase-1, heme oxidase-1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein-induced activation of the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor- (NF-) κB activation and modulated NF-κB-responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2-mediated oxidative stress and NLRP3/NF-κB inflammatory pathways in acinar cells, thereby protecting against AP.

High-Fat Diet Aggravates Acute Pancreatitis via TLR4-Mediated Necroptosis and Inflammation in Rats

“…AP is an acute inflammatory disease of the digestive system. Although the pathogenesis of AP still remains controversial, the oxidative stress pathway is recognized as one of the classical underlying mechanisms in the early phase of AP [19]. Under physiological conditions, oxidative stress damage could be inhibited by antioxidant defense system, consisted of nonenzymatic antioxidants to scavenge reactive oxygen species (ROS) and antioxidase to catalyze the elimination of ROS accumulation [20].…”

Kaempferide Protects against Myocardial Ischemia/Reperfusion Injury through Activation of the PI3K/Akt/GSK-3β Pathway

“…GSK3- β has been shown to function as a negative regulator of Nrf2, a protein involved in signaling pathways that plays a critical role in the defense against oxidative and toxicological stress via upregulation of antioxidant and detoxifying enzyme expression [ 32 , 33 ]. In addition, Nrf2 activation has also been reported to protect against inflammation [ 34 ]. Nrf2 has been shown to attenuate inflammatory responses through a number of mechanisms, including the induction of the anti-inflammatory enzyme, hemeoxygenase-1(HO-1) [ 35 ], the negative regulation of proinflammatory cytokine expression [ 36 ], and chemokine expression [ 37 ].…”

Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

“…Under the physiology condition, Nrf2 is located in the cytoplasm. When Nrf2 is activated, it is translocated into the nucleus and combined with the ARE to induce a series of cytoprotective enzymes such as HO-1 [49, 50] and NQO-1 [51, 52] to enhance the antioxidant capacity of cells and protect cells from the oxidative injury [53, 54]. In the present studies, the elevation of Nrf2, HO-1, and NQO-1 at mRNA and protein levels found in SE rats 24 hrs but not 7 days following Li-Pc injection indicated that epileptic seizures could transiently activate Nrf2-ARE pathway [55].…”