Combating diabetes complications by 1-Fe, a corrole-based catalytic antioxidant

Area of Science:

• Biochemistry
• Toxicology
• Pharmacology

Background:

• Diabetes complications arise from oxidative stress due to reactive oxygen and nitrogen species (ROS/RNS).
• Corrole-based catalysts offer potential therapeutic benefits by decomposing ROS/RNS.
• Assessing catalyst safety and efficacy is critical for clinical translation.

Purpose of the Study:

• To evaluate the safety and therapeutic potential of the corrole-based catalyst 1-Fe in managing diabetes complications.
• To investigate the toxicity profile, including cardiotoxicity and mutagenicity, of 1-Fe.
• To compare the efficacy of 1-Fe with alpha-lipoic acid in a diabetic rat model.

Main Methods:

• Cardiotoxicity and mutagenic potential assessed using hERG and AMES tests.
• General toxicity evaluated in rats at varying doses.
• Diabetes induced in rats using streptozotocin; treated with 1-Fe (20 mg/kg/day).
• Cataract development, kidney function, and lipid profiles were monitored.

Main Results:

• 1-Fe demonstrated safety in hERG and AMES tests, with mild adverse effects in rats only at 300 mg/kg/day.
• In diabetic rats, 1-Fe (20 mg/kg/day) prevented/reduced cataracts, improved kidney function, and lowered cholesterol and triglycerides.
• 1-Fe showed comparable or superior benefits to alpha-lipoic acid.

Conclusions:

• The corrole-based catalyst 1-Fe is safe for further development towards clinical trials.
• 1-Fe effectively mitigates key diabetes complications by disarming ROS/RNS and improving lipid profiles.
• 1-Fe presents a promising therapeutic candidate for managing diabetic complications.