TY - JOUR
T1 - Calcium dobesilate prevents the oxidative stress and inflammation induced by diabetes in the retina of db/db mice
AU - Bogdanov, Patricia
AU - Solà-Adell, Cristina
AU - Hernández, Cristina
AU - García-Ramírez, Marta
AU - Sampedro, Joel
AU - Simó-Servat, Olga
AU - Valeri, Marta
AU - Pasquali, Christian
AU - Simó, Rafael
PY - 2017/10/1
Y1 - 2017/10/1
N2 - © 2017 Elsevier Inc. 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 (200 mg/kg/day) or vehicle for 15 days. 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.
AB - © 2017 Elsevier Inc. 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 (200 mg/kg/day) or vehicle for 15 days. 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.
KW - Calcium dobesilate
KW - Diabetic retinopathy
KW - Inflammation
KW - Oxidative stress
KW - Retinal endothelial cells
KW - db/db mouse
U2 - 10.1016/j.jdiacomp.2017.07.009
DO - 10.1016/j.jdiacomp.2017.07.009
M3 - Article
SN - 1056-8727
VL - 31
SP - 1481
EP - 1490
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
IS - 10
ER -