Resorcylidene Aminoguanidine (RAG) Improves Cardiac Mitochondrial Bioenergetics Impaired by Hyperglycaemia in a Model of Experimental Diabetes

Abstract

Diabetes is associated with a mitochondrial dysfunction. Hyperglycaemia is also clearly recognized as the primary culprit in the pathogenesis of cardiac complications. In response to glycation and oxidative stress, cardiac mitochondria undergo cumulative alterations, often leading to heart deterioration. There is a continuous search for innovative treatment strategies for protecting the heart mitochondria from the destructive impact of diabetes. Aminoguanidine derivatives have been successfully used in animal model studies on the treatment of experimental diabetes, as well as the diabetes-driven dysfunctions of peripheral tissues and cells. Considerable attention has been paid particularly to β-resorcylidene aminoguanidine (RAG), often shown as the efficient anti-glycation and anti-oxidant agent in both animal studies and in vitro experiments. The aim of the present study was to test the hypothesis that RAG improves oxidative phosphorylation and electron transport capacity in mitochondria impaired by hyperglycaemia. Diabetes mellitus was induced in Wistar rats by a single intraperitoneal injection of streptozotocin (70 mg/kg body weight). Heart mitochondria were isolated from healthy rats and rats with streptozotocin-diabetes. Mitochondrial respiratory capacity was measured by high resolution respirometry with the OROBOROS Oxygraph-2k according to experimental protocol including respiratory substrates and inhibitors. The results revealed that RAG protects the heart against diabetes-associated injury by improving the mitochondrial bioenergetics, thus suggesting a possible novel pharmacological strategy for cardioprotection.

Amelioration of altered antioxidant enzymes activity and glomerulosclerosis by coenzyme Q10 in alloxan-induced diabetic rats

“…Treatment of diabetic animals with coenzyme Q10 significantly inhibited an increase of serum and kidney lipid peroxidation in comparison with the untreated diabetic animals. There are reports that natural antioxidants such as vitamin E, vitamin C, lipoic acid, aminoguanidine (Di Naso et al, 2010;Labieniec-Watala, Siewiera, & Jozwiak, 2011), turine, N-acetylcysteine, allopurinol lycopene (Ahmad et al, 2012), and natural phenolic compounds have protective effects on lipid peroxidation in diabetics disease (Bose & Agrawal, 2007;Kaliora & Dedoussis, 2007). Also there are reports that coenzyme Q10 has protective effects on lipid peroxidation.…”

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

“…For the present study, a diabetic model is defined as an experimental model characterized by a non-fasting blood glucose measurement of 16.7 mmol/L or higher, detected by two consecutive measurements, following the second STZ injection [24,25] . Thirty-two animals were divided equally and evenly into four groups: the control group (Ctrl), the matrine group (Mat), the DCM group (DCM) and the treatment group (DCM+Mat).…”

Activation of protein kinase C‑α/heme oxygenase‑1 signaling pathway improves mitochondrial dynamics in lipopolysaccharide‑activated NR8383 cells

“…According to the methods described by Carlson et al (27), mitochondria were isolated and stored at 0˚C in a buffer containing 250 mM sucrose, 10 mM Tris-hydrochloric acid (HCl), 0.5 mM EDTA, and 0.5 g/l fatty acid-free bovine serum albumin (BSA; Invitrogen; Thermo Fisher Scientific, Inc.) (pH 7.2) (21). The respiratory control ratio (RCR) was measured by a Clark-type oxygen electrode (Hansatech, King's Lynn, United Kingdom) at 37˚C (28). The respiration medium contained 110 mM sucrose, 60 mM K-lactobionate, 0.5 mM EGTA, 1 g/l BSA essentially fatty acid-free, 3 mM MgCl 2 , 20 mM taurine, 10 mM KH 2 PO 4 , 20 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (pH 7.1) and 280 IU/ml catalase (Nanjing Jiancheng Bioengineering Institute) (28).…”

“…The respiratory control ratio (RCR) was measured by a Clark-type oxygen electrode (Hansatech, King's Lynn, United Kingdom) at 37˚C (28). The respiration medium contained 110 mM sucrose, 60 mM K-lactobionate, 0.5 mM EGTA, 1 g/l BSA essentially fatty acid-free, 3 mM MgCl 2 , 20 mM taurine, 10 mM KH 2 PO 4 , 20 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (pH 7.1) and 280 IU/ml catalase (Nanjing Jiancheng Bioengineering Institute) (28). A 60-µl mitochondrial suspension was incubated in the chamber for 10 min at 25˚C.…”