Aspirin Ameliorates Pancreatic Inflammation and Fibrosis by Inhibiting COX-2 Expression in Experimental Chronic Pancreatitis

Abstract

Aim Chronic pancreatitis (CP) is a complex and intractable disease mainly manifested as chronic inflammation and fibrosis. Aspirin(acetylsalicylic acid, ASA) has been reported to be used in the treatment of acute pancreatitis (AP), but its effectiveness on CP is unclear. This study aimed to investigate the therapeutic effects of ASA in CP mice. Methods A murine model of CP was induced by intraperitoneal injection with 20% L-arginine. After one week of L-arginine administration, mice in the ASA treatment group were administered aspirin (100mg/kg/d) by intragastric gavage. At two, four, and six weeks after the first injection of L-arginine, mice were euthanized and the pancreas was collected for histological and molecular analysis. A second model of CP (caeruelin-induced) was used as a validation experiment to test the effect of ASA. Results L-arginine-induced CP resulted in over-expression of the inflammatory enzyme cyclooxygenase (COX)-2. COX-2 expression decreased after ASA treatment. Pancreatic-injury inflammatory response (measured by changes in amylase, CK-19, F4/80, CD3, MCP-1, IL-6) and fibrosis degree (measured by expression of COL1A1, MMP-1 and TIMP-1) was reduce in ASA -treated mice model. The therapeutic effect of ASA was also observed in caeruelin-induced CP. Conclusion ASA has an ameliorating effect in murine models of CP through inhibition of pancreatic inflammation and fibrosis, which may be a promising option for clinical treatment.

Low-Dose Acetylsalicylic Acid and Mitochondria-Targeted Antioxidant Mitoquinone Attenuate Non-Alcoholic Steatohepatitis in Mice

“…On the other hand, the beneficial effects of ASA on inflammation can also be explained by the decreased expression of COX-1, COX-2, TNFα, and IL-6 and the increased expression of anti-inflammatory IL-10. The inhibitory effect of ASA on COX-2 expression has also been shown in other recent studies, but the decrease in COX-2 expression could be promoted by the reduced levels of TNF-α as well [ 20 , 21 , 22 , 23 , 24 ]. In line with the results of our study, it has been shown that, in mice fed with a methionine- and choline-deficient diet, hepatic expression of COX-2 messenger RNA and protein was significantly higher than controls, paralleling the increase in the levels of TNF-α and IL-6 and the development of steatohepatitis; pharmacological inhibition of COX-2 ameliorated the severity of experimental steatohepatitis [ 25 ].…”

The hepatoprotective effect of aspirin on carbon tetrachloride‑induced hepatic fibrosis via inhibition of TGFβ‑1 pathway and pro‑inflammatory cytokines IL‑1β and COX‑2 in rats

“…In addition, COX-2 serves an important role in the progression of liver fibrosis. Emerging evidence has suggested that COX-2 serves a role in the development of fibrosis in the kidney, pancreas and liver and that inhibition of COX-2 expression can have an anti-fibrotic effect (43)(44)(45). Therefore, the protective effect of aspirin against CCl 4 -induced liver fibrosis in rats may also be mediated by inhibition of COX-2.…”

Management of chronic pancreatitis: recent advances and future prospects

“…Except for these drugs used in clinical practice, there are also other drugs being tested for efficacy in animal experiments, including catechin hydrate, 57 nintedanib, 58 aspirin, 59 and pirfenidone. 60 But these preliminary studies are only pilot explorations for the possibility of other drugs without sufficient significance in clinical management.…”