Abstract
Severe acute pancreatitis (SAP) is associated with high rates of mortality and morbidity. Chitosan oligosaccharides (COSs) are agents with antioxidant properties. We developed porous COS@SiO2 nanocomposites to study the protective effects and mechanisms of COS nanomedicine for the treatment of acute pancreatitis. Porous COS@SiO2 nanocomposites released COSs slowly under pH control, enabling sustained release and maintaining the drug at a higher concentration. This study aimed to determine whether porous COS@SiO2 nanocomposites ameliorate SAP and associated lung injury. The SAP model was established in male C57BL/6 mice by intraperitoneal injection of caerulein. The expression levels of myeloperoxidase, malondialdehyde, superoxide dismutase, nuclear factor-kappa B (NF-κB), the NOD-like receptor protein 3 (NLRP3) inflammasome, nuclear factor E2-related factor 2 (Nrf2), and inflammatory cytokines were detected, and a histological analysis of mouse pancreatic and lung tissues was performed. In the SAP groups, systemic inflammation and oxidative stress occurred, and pathological damage to the pancreas and lung was obvious. Combined with porous COS@SiO2 nanocomposites before treatment, the systemic inflammatory response was obviously reduced, as were oxidative stress indicators in targeted tissues. It was found that Nrf2 was significantly activated in the COS@SiO2 treatment group, and the expressions of NF-κB and the NLRP3 inflammasome were notably decreased. In addition, this protective effect was significantly weakened when Nrf2 signaling was inhibited by ML385. This demonstrated that porous COS@SiO2 nanocomposites activate the Nrf2 signaling pathway to inhibit oxidative stress and reduce the expression of NF-κB and the NLRP3 inflammasome and the release of inflammatory factors, thus blocking the systemic inflammatory response and ultimately ameliorating SAP and associated lung injury.
Highlights
Acute pancreatitis (AP) is a common acute abdomen presentation in the clinic with increasing morbidity in recent years
After loading the Chitosan oligosaccharides (COSs), COS@SiO2 appeared as COS absorption peaks (Figure 1B), indicating that the COSs had been incorporated into the porous SiO2
The COS release was much more rapid and the release rate was higher in an alkaline environment, which could be attributed to the enhanced aqueous solubility of COSs (Figure 1D)
Summary
Acute pancreatitis (AP) is a common acute abdomen presentation in the clinic with increasing morbidity in recent years. The severity of AP can be described as mild, moderate, or severe according to the local injury to the pancreas and systemic injury to other organs (Banks et al, 2013). Severe acute pancreatitis (SAP) is a serious illness with rapid onset and a high fatality rate. It is characterized by the systemic inflammatory response syndrome, the multiple organ dysfunction syndrome, sepsis, and other complications (Bi et al, 2015). Acute lung injury (ALI) is one of the most serious and earliest complications of SAP. ALI is described as an important risk factor for death in the early stages of SAP with a high mortality rate in the range of 30–40% (Zhou et al, 2010)
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