Calcium dobesilate prevents the oxidative stress and inflammation induced by diabetes in the retina of db/db mice.

Abstract

AIM:

Calcium dobesilate (CaD) is beneficial in early stages of diabetic retinopathy (DR), but its mechanisms of action remains to be elucidated. The aim was to investigate the effect of CaD on proinflammatory cytokines and oxidative stress.

METHODS:

db/db mice were randomly assigned to daily oral treatment with CaD (200mg/kg/day) or vehicle for 15days. Biomarkers of oxidative stress (dihydroethidium, malondialdehyde), NF-κB, and proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, MCP-1) were examined in the retina by immunohistochemical analysis. Cultures of human retinal endothelial cells (HRECs) were used for complementary experiments.

RESULTS:

CaD significantly reduced the biomarkers of oxidative stress in the retina of db/db mice. In addition, CaD prevented the increase of NF-κB, IL-6, IL-8, TNF-α and MCP-1 induced by diabetes. CaD inhibited the activation of NF-kβ induced by IL-1β by preventing IKKB-α phosphorylation in HRECs and reduced the upregulation of IL-6 and IL-18 induced by TNF-α in a dose-dependent manner.

CONCLUSION:

Our results suggest that antioxidant and antiinflammatory effects are crucial in accounting for the effectiveness of CaD for treating DR.

• Authors: Patricia Bogdanov, Cristina Solà-Adell, Cristina Hernández, Marta García-Ramírez, Joel Sampedro, Olga Simó-Servat, Marta Valeri, Christian Pasquali, Rafael Simó
• Journal: Journal of diabetes and its complications (J Diabetes Complications) Vol. 31 Issue 10 Pg. 1481-1490 (Oct 2017) ISSN: 1873-460X [Electronic] United States
• PMID: 28847447 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Biomarkers
• Cytokines
• Neuroprotective Agents
• Calcium Dobesilate
• I-kappa B Kinase
• Ikbkb protein, rat

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Antioxidants (pharmacology, therapeutic use)
• Biomarkers (metabolism)
• Calcium Dobesilate (pharmacology, therapeutic use)
• Cells, Cultured
• Crosses, Genetic
• Cytokines (antagonists & inhibitors, metabolism)
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Diabetic Retinopathy (immunology, metabolism, pathology, prevention & control)
• Humans
• I-kappa B Kinase (metabolism)
• Male
• Mice, Mutant Strains
• Mice, Transgenic
• Neuroprotective Agents (therapeutic use)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Protein Processing, Post-Translational (drug effects)
• Random Allocation
• Retina (drug effects, immunology, metabolism, pathology)
• Retinitis (complications, immunology, metabolism, prevention & control)