Ilya B Zavodnik, Tatsiana A Kavalenia, Siarhei N Kirko, Elena B Belonovskaya, Irina A Kuzmitskaya, Yulia V Eroshenko, Elena A Lapshina, Vyacheslav U Buko
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引用次数: 0
Abstract
Background and purpose: Cardiac mitochondria dysfunction plays a central pathophysiological role in the abnormal glucose metabolism in the heart during diabetic cardiomyopathy. The present study evaluated the effects of flavonoid glycoside naringin treatment on the interconnection between changes in cardiac mitochondria oxygen consumption, membrane potential and mitochondrial Ca2+ sensitivity during type 1 diabetes.
Experimental approach: Type 1 diabetes was induced by an intraperitoneal injection of streptozotocin (40 mg/kg) in rats and islet morphology, glucose and insulin levels, changes in heart mitochondria respiration, membrane potential, spontaneous and Ca2+ - induced mitochondrial permeability transition (MPT) pore opening were evaluated.
Key results: Diabetes resulted in typical signs of hyperglycaemia, which were accompanied by a rat cardiac mitochondria dysfunction, manifested by decreased V2 and V3 rates of oxygen consumption, while the initial membrane potential value remained unchanged. The rates of Ca2+-induced MPT pore opening and Ca2+-induced membrane potential dissipation in isolated mitochondria decreased under type 1 diabetes. The naringin treatment (40 mg/kg of the body weight, 4 weeks) partially recovered impaired cardiac mitochondria respiration, decreased spontaneous and increased Ca2+-induced MPT pore opening, improved pancreatic islets morphology and dystrophic changes, lowered glycated haemoglobin and blood plasma urea, and decreased the oxidative stress level with glucose or insulin concentrations remaining unchanged in diabetic animals.
Conclusions: Naringin administration demonstrated beneficial effects during type 1 diabetes and represents a promising therapeutic (or nutraceutical) approach for diabetes treatment.
期刊介绍:
ADMET and DMPK is an open access journal devoted to the rapid dissemination of new and original scientific results in all areas of absorption, distribution, metabolism, excretion, toxicology and pharmacokinetics of drugs. ADMET and DMPK publishes the following types of contributions: - Original research papers - Feature articles - Review articles - Short communications and Notes - Letters to Editors - Book reviews The scope of the Journal involves, but is not limited to, the following areas: - physico-chemical properties of drugs and methods of their determination - drug permeabilities - drug absorption - drug-drug, drug-protein, drug-membrane and drug-DNA interactions - chemical stability and degradations of drugs - instrumental methods in ADMET - drug metablic processes - routes of administration and excretion of drug - pharmacokinetic/pharmacodynamic study - quantitative structure activity/property relationship - ADME/PK modelling - Toxicology screening - Transporter identification and study