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Recombinant human hepatocyte growth factor provides protective effects in cerulein‐induced acute pancreatitis in mice
Author(s) -
PalestinoDominguez Mayrel,
PelaezLuna Mario,
LazzariniLechuga Roberto,
RodriguezOchoa Ignacio,
Souza Veronica,
Miranda Roxana U.,
PerezAguilar Benjamín,
Bucio Leticia,
Marquardt Jens U.,
GomezQuiroz Luis Enrique,
GutierrezRuiz Maria Concepcion
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26444
Subject(s) - pancreatitis , acute pancreatitis , proinflammatory cytokine , hepatocyte growth factor , medicine , oxidative stress , endocrinology , edema , glutathione , inflammation , pancreas , ceruletide , cytokine , receptor , chemistry , cholecystokinin , enzyme , biochemistry
Acute pancreatitis is a multifactorial disease associated with profound changes of the pancreas induced by release of digestive enzymes that lead to increase in proinflammatory cytokine production, excessive tissue necrosis, edema, and bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c‐Met have been observed in different chronic and acute pancreatic diseases including experimental models of acute pancreatitis. In the present study, we investigated the protective effects induced by the recombinant human HGF in a mouse model of cerulein‐induced acute pancreatitis. Pancreatitis was induced by 8 hourly administrations of supramaximal cerulein injections (50 µg/kg, ip). HGF treatment (20 µg/kg, iv), significantly attenuated lipase content and amylase activity in serum as well as the degree inflammation and edema overall leading to less severe histologic changes such as necrosis, induced by cerulein. Protective effects of HGF were associated with activation of pro‐survival pathways such as Akt, Erk1/2, and Nrf2 and increase in executor survival‐related proteins and decrease in pro‐apoptotic proteins. In addition, ROS content and lipid peroxidation were diminished, and glutathione synthesis increased in pancreas. Systemic protection was observed by lung histology. In conclusion, our data indicate that HGF exerts an Nrf2 and glutathione‐mediated protective effect on acute pancreatitis reflected by a reduction in inflammation, edema, and oxidative stress.