Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone.

Abstract

High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The used methods include weight measurement, glucose-related measurements-like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results-electroretinography and Western Blot. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.

• Authors: Zita Wachal, Mariann Bombicz, Dániel Priksz, Csaba Hegedűs, Diána Kovács, Adrienn Mónika Szabó, Rita Kiss, József Németh, Béla Juhász, Zoltán Szilvássy, Balázs Varga
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 6 (Mar 19 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32204537 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Blood Glucose
• Hydroxamic Acids
• Hypoglycemic Agents
• Insulin
• Oximes
• Piperidines
• Protective Agents
• Metformin
• BGP 15
• Glyburide
• Pioglitazone

Topics

• Animals
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (blood, physiopathology)
• Diabetic Retinopathy (prevention & control)
• Disease Models, Animal
• Electroretinography
• Glyburide (pharmacology)
• Humans
• Hydroxamic Acids (chemistry, pharmacology)
• Hypoglycemic Agents (pharmacology)
• Insulin (pharmacology)
• Male
• Metformin (pharmacology)
• Molecular Structure
• Oximes (chemistry, pharmacology)
• Pioglitazone (pharmacology)
• Piperidines (chemistry, pharmacology)
• Protective Agents (chemistry, pharmacology)
• Rats
• Rats, Wistar
• Retina (drug effects, physiopathology)