Vitamin K3 attenuates cerulein-induced acute pancreatitis through inhibition of the autophagic pathway.
OBJECTIVE
The discovery of novel and effective treatment methods would be of great help to patients with acute pancreatitis. The aims of this study were to determine the inhibitory effects of vitamin K3 (VK3) against cerulein-induced acute pancreatitis in mice and to examine the mechanisms behind these effects.


METHODS
Acute pancreatitis in mice was induced by intraperitoneal injection of cerulein 6 times at hourly intervals. Vitamin K3 was administered once before the first injection of cerulein or twice before and after the first injection of cerulein. The degrees of inflammation and autophagy in the pancreatic tissue were estimated by histological examination, measurement of enzyme activity, confocal microscopy, and Western blotting. The inhibitory effects of VK3 against rapamycin-induced autophagy were also examined using HeLa cells stably expressing green fluorescent protein LC3.


RESULTS
Cerulein-induced acute pancreatitis was markedly attenuated by the administration of VK3. In addition, VK3 led to the inhibition of cerulein-evoked autophagic changes and colocalization of autophagosomes and lysosomes in the pancreatic tissue. Vitamin K3 also reduced rapamycin-induced autophagy in HeLa/green fluorescent protein LC3 cells.


CONCLUSIONS
Our data suggest that the administration of VK3 reduces pancreatic inflammation in acute pancreatitis through inhibition of the autophagic pathway. Vitamin K3 may be an effective therapeutic strategy against acute pancreatitis.
Chinzei
Ryo
R
Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, and Division of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan.
Masuda
Atsuhiro
A
Nishiumi
Shin
S
Nishida
Masayuki
M
Onoyama
Mitsuko
M
Sanuki
Tsuyoshi
T
Fujita
Tsuyoshi
T
Moritoh
Satoshi
S
Itoh
Tomoo
T
Kutsumi
Hiromu
H
Mizuno
Shigeto
S
Azuma
Takeshi
T
Yoshida
Masaru
M
D000208:Acute Disease; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002108:Ceruletide / Q000633:toxicity*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D010588:Phagosomes / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D024482:Vitamin K 2 / Q000494:pharmacology; D024483:Vitamin K 3 / Q000627:therapeutic use*
D024482:Vitamin K 2; D024483:Vitamin K 3; D002108:Ceruletide; D020123:Sirolimus