Silymarin induces recovery of pancreatic function after alloxan damage in rats.

Abstract

Alloxan has been widely used to produce experimental diabetes mellitus syndrome. This compound causes necrosis of pancreatic beta-cells and, as is well known, induces oxidant free radicals which play a relevant role in the etiology and pathogenesis of both experimental and human diabetes mellitus. Previously we have reported hypoglycemic and antilipoperoxidative actions of silymarin in serum and pancreatic tissue respectively. The aim of this study was to test whether silymarin could reduce the hyperglycemia and revert the pancreatic damage in alloxan treated rats, tested with silymarin in two protocols: using both compounds simultaneously for four or eight doses, or using the compound 20 days after alloxan administration for 9 weeks. Serum glucose and insulin were determined, and pancreatic fragments were used for histology and insulin immunohistochemistry. Pancreatic islets were isolated to assess insulin and Pdx1 mRNA expression by RT-PCR. Our results showed that 72 hours after alloxan administration, serum glucose increased and serum insulin decreased significantly, whereas pancreatic tissue presented morphological abnormalities such as islet shrinkage, necrotic areas, loss of cell organization, widespread lipoid deposits throughout the exocrine tissue, and loss of beta cells, but insulin and glucagon immunoreactivity was scattered if any. In contrast the pancreatic tissue and both insulin and glucose serum levels of rats treated with silymarin were similar to those of control animals. In addition, insulin and glucagon immunoreactive cells patterns in Langerhans islets were also normal, and normal insulin and Pdx1 mRNA expression patterns were detected during pancreatic recovery in Langerhans islets. The overall results suggest that silymarin induces pancreatic function recovery demonstrated by insulin and glucagon expression protein and normoglycemia after alloxan pancreatic damage in rats.

• Authors: C Soto, R Mena, J Luna, M Cerbón, E Larrieta, P Vital, E Uría, M Sánchez, R Recoba, H Barrón, L Favari, A Lara
• Journal: Life sciences (Life Sci) Vol. 75 Issue 18 Pg. 2167-80 (Sep 17 2004) ISSN: 0024-3205 [Print] Netherlands
• PMID: 15325843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2004 Elsevier Inc.

Chemical References

• Blood Glucose
• Homeodomain Proteins
• Insulin
• Protective Agents
• Silymarin
• Trans-Activators
• pancreatic and duodenal homeobox 1 protein
• RNA
• Glyceraldehyde-3-Phosphate Dehydrogenases

Topics

• Animals
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Diabetes Mellitus, Experimental (drug therapy, pathology, physiopathology)
• Glyceraldehyde-3-Phosphate Dehydrogenases (metabolism)
• Homeodomain Proteins
• Immunohistochemistry
• Insulin (blood)
• Islets of Langerhans (pathology, physiopathology)
• Male
• Pancreas (pathology, physiopathology)
• Protective Agents (therapeutic use)
• RNA (biosynthesis, isolation & purification)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• Silymarin (therapeutic use)
• Survival Analysis
• Trans-Activators (biosynthesis, genetics)