Ann Surg Treat Res.  2019 Dec;97(6):271-281. 10.4174/astr.2019.97.6.271.

Examination of protective and therapeutic effects of ruscogenin on cerulein-induced experimental acute pancreatitis in rats

• Ercan G
• Ä°lbar Tartar R
• Solmaz A
• Gulcicek O
• Karagulle
• Meric S
• Cayoren H
• Kusaslan R
• Kemik A
• Gokceoglu Kayali D
• Cetinel S
• Celik A

• KMID: 2464782
• DOI: http://doi.org/10.4174/astr.2019.97.6.271

Abstract

PURPOSE
To determine the potential protective and therapeutic effects and action mechanism of ruscogenin on cerulein-induced acute pancreatitis (AP) model in rats.
METHODS
Overall, 32 rats were attenuated to the sham (2-mL/kg/day isotonic solution for 4 weeks), control (20-µg/kg cerulein-induced AP for 12 hours), prophylaxis groups (cerulein-induced AP following 3-mL/kg/day ruscogenin for 4 weeks) and treatment (3-mL/kg/day ruscogenin following cerulein-induced AP for 12 hours). Blood samples were collected for biochemical analysis of nitric oxide synthase 1 (NOS1/neuronal NOS), malondialdehyde (MDA) and intercellular adhesion molecule 1 (ICAM-1). After sacrification, pancreas tissues were collected and prepared for light microscopic (hematoxylin and eosin), immunohistochemical (nuclear factor kappa B) and biochemical analysis (tumor necrosis factor-alpha [TNF-α], interleukin-6 and 1β [IL-6 and IL-1β], CRP, high-sensitivity CRP [hs-CRP] amylase, lipase, and ICAM-1). Ultrastructural analysis was performed by transmission electron microscopy.
RESULTS
The protective and therapeutic actions of ruscogenin were accomplished by improvements in histopathology, by decreasing blood cytokine levels of CRP, hs-CRP levels, TNF-α, IL-6, IL-1β, ICAM-1, by reducing the pancreatic enzymes amylase and lipase in blood, and by suppressing the expression of nuclear factor kappa B, ICAM-1, and NOS-1, but not MDA in pancreatic tissues. Ruscogenin also improved cerulein-induced ultrastructural degenerations in endocrine and exocrine cells, especially in treatment group.
CONCLUSION
The present findings have demonstrated the beneficial protective and therapeutical effects of ruscogenin, nominating it as a highly promising supplementary agent to be considered in the treatment of AP, and even as a protective agent against the damages induced by disease.

Keyword

Ceruletide; NF-kappa B; Pancreas; Pancreatitis; Ruscogenin

MeSH Terms

Amylases
Animals
Ceruletide
Intercellular Adhesion Molecule-1
Interleukin-6
Lipase
Malondialdehyde
Microscopy, Electron, Transmission
Necrosis
NF-kappa B
Nitric Oxide Synthase
Pancreas
Pancreatitis*
Rats*
Therapeutic Uses*
Amylases
Ceruletide
Intercellular Adhesion Molecule-1
Interleukin-6
Lipase
Malondialdehyde
NF-kappa B
Nitric Oxide Synthase
Therapeutic Uses

Figure

• 

  Fig. 1 Pancreatic tissues of experimental acute pancreatitis. (A) Sham group. (B) Control group. (C) Prophylaxis group. (D) Treatment group. Arrowhead: cytoplasmic vacuole, Asterisk: necrosis, Arrow: damage in the unity of acinar cells. H&E stain. Scale bar represents 50 µm.

• 

  Fig. 2 Nuclear factor kappa B (NF-κB) immunohistochemistry of experimental acute pancreatitis. (A) Sham group. (B) Control group. (C) Prophylaxis group. (D) Treatment group. Arrows: NF-κB positive cells. Scale bar represents 50 µm.

• 

  Fig. 3 Immunohistochemical scores of nuclear factor kappa B (NF-κB) in pancreatic tissues of acute pancreatitis rats. Values are presented as mean ± standard error of the mean. a)P < 0.001 vs. sham group, b)P < 0.001 vs. control group, Kruskal-Wallis test (nonparametric analysis of variance) and Dunn multiple comparisons test.

• 

  Fig. 4 Ultrastructural micrographs of experimental acute pancreatitis. N: nucleus, mt: mitochondria, C: capillary, RER: rough endoplasmic reticulum, ZG: zymogen granules, V: vacuole. Bars: 1 µm (for exocrine pancreases of sham, control, and treatment groups); 2 µm (for endocrine pancreas of sham and exocrine pancreas of prophylaxis group); 500 nm (for endocrine pancreases of control, prophylaxis, and treatment groups).

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