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Preventive effects of benfotiamine in chronic diabetic complications
Rana Chakrabarti1, Megan Chen1, Weihua Liu1
1Department of Pathology, The University of Western Ontario, London, ON, Canada.
Unlabelled:
Aims/Introduction: In diabetes, increased oxidative stress as a result of damage to the electron transport chain can lead to tissue injury through upregulation of multiple vasoactive factors and extracellular matrix proteins. Benfotiamine, a lipid soluble thiamine derivative, through reducing mitochondrial superoxide production, blocks multiple pathways leading to tissue damage in hyperglycemia. We investigated if treatment with benfotiamine can prevent diabetes-induced production of vasoactive factors and extracellular matrix proteins, and whether such effects are tissue-specific. We also examined whether effects of benfotiamine are mediated through a nuclear mechanism.
Materials And Methods:
Retinal, renal and cardiac tissues from the streptozotocin-induced diabetic rats were examined after 4 months of follow up. mRNA levels were quantified using real-time RT-PCR. Protein levels were quantified using western blot and ELISA. Cellular expressions of 8-Hydroxy-2'-deoxyguanosine, a marker of nuclear DNA damage and Phospho-H2AX were also examined.
Results:
Diabetic animals showed hyperglycemia, glucosuria, increased urinary albumin/creatine ratio and loss of bodyweight. In the kidneys, heart and retina, diabetes caused increased production of endothelin-1, transforming growth factor-β1, vascular endothelial growth factor and augmented extracellular matrix proteins (collagen, fibronectin [FN] and its splice variant extradomain B containing FN), along with evidence of structural alterations, characteristic of diabetes-induced tissue damage. Such changes were prevented by benfotiamine. Furthermore, benfotiamine prevented diabetes-induced oxidative DNA damage and upregulation of p300, a histone acetylator and a transcription coactivator.
Conclusions:
Data from the present study suggest that benfotiamine is effective in preventing tissue damage in diabetes and at the transcriptional level such effects are mediated through prevention of p300 upregulation. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00077.x, 2010).
Insights
Benfotiamine, a thiamine derivative, effectively prevents diabetes-induced tissue damage by reducing oxidative stress and blocking harmful pathways. Its protective effects are linked to preventing p300 upregulation at the transcriptional level.
Area of Science:
- Endocrinology
- Diabetology
- Molecular Biology
Background:
- Diabetes mellitus is characterized by hyperglycemia, leading to increased oxidative stress and subsequent tissue injury.
- Oxidative stress in diabetes damages the electron transport chain, upregulating vasoactive factors and extracellular matrix proteins.
- Benfotiamine, a lipid-soluble thiamine derivative, mitigates hyperglycemia-induced damage by reducing mitochondrial superoxide production.
Purpose of the Study:
- To investigate benfotiamine's efficacy in preventing diabetes-induced production of vasoactive factors and extracellular matrix proteins.
- To determine if benfotiamine's effects are tissue-specific (retina, kidney, heart).
- To examine the potential nuclear mechanism underlying benfotiamine's protective actions.
Main Methods:
- Streptozotocin-induced diabetic rats were used, with tissues (retina, kidney, heart) analyzed after 4 months.
- Gene and protein expression levels of key factors (endothelin-1, TGF-β1, VEGF, ECM proteins) were quantified.
- Oxidative DNA damage markers (8-OHdG, γH2AX) and p300 levels were assessed.
Main Results:
- Diabetes induced hyperglycemia, albuminuria, and tissue damage, marked by increased endothelin-1, TGF-β1, VEGF, and extracellular matrix deposition.
- Benfotiamine treatment prevented these diabetes-induced changes in the retina, kidney, and heart.
- Benfotiamine administration inhibited diabetes-associated oxidative DNA damage and the upregulation of p300.
Conclusions:
- Benfotiamine demonstrates effectiveness in preventing diabetic tissue damage across multiple organs.
- The protective effects of benfotiamine appear to be mediated at the transcriptional level via the prevention of p300 upregulation.
- These findings highlight benfotiamine as a potential therapeutic agent for managing diabetic complications.