<p>Cardioprotective effects of a ruthenium (II) Schiff base complex in diet-induced prediabetic rats</p>

Abstract

Background Prediabetes and the onset of cardiovascular diseases (CVD) are strongly related. Prolonged hyperglycemia has been identified as a major contributing factor in the pathogenesis of CVD and diabetic complications. The management of hyperglycemia and prediabetes-associated vascular complications rely on pharmacotherapy and lifestyle intervention strategies. However, patients still take the conventional drugs and neglect lifestyle intervention; therefore, newer alternative drugs are required. The synthesized ruthenium Schiff base complex has been shown to have elevated biological and antidiabetic activity. Thus, the research investigated the cardio-protective effects of ruthenium (II) Schiff base complex in diet-induced prediabetic (PD) rats. Materials and methods The rats were randomly allocated to respective groups and treated for 12 weeks. Ruthenium (15 mg/kg) was administered to PD rats once a day every third day. Blood pressure and plasma glucose were monitored throughout the study. Blood and heart tissue were collected for biochemical assays. Results Ruthenium complex with dietary intervention lead to reduced mean arterial blood pressure which correlated with a restored heart to body weight ratio. Additionally, there was a significant decrease in tissue malondialdehyde and increased superoxide dismutase and glutathione peroxidase concentration in both the plasma and heart tissue. Furthermore, there was a decrease in plasma triglycerides, low-density lipoprotein with an increased high-density lipoprotein concentration in ruthenium-treated rats. This was further evidenced by reduced plasma tumor necrosis factor-α, IL-6, and cardiac C-reactive protein concentrations in ruthenium-treated rats. Conclusion Ruthenium coupled with dietary intervention decreased the risk of developing cardiac injury, thus preventing CVD in prediabetes. Therefore, this complex may be a beneficial therapeutic agent in the prevention of PD cardiovascular complications.

The dysregulation of the hypothalamic–pituitary–adrenal axis in diet-induced prediabetic male Sprague Dawley rats

“…However, studies indicate that complications often associated with T2DM begin during pre-diabetes [ 7 ]. Previous studies done in our laboratory have found that micro- and macrovascular changes leading to complications such as cardiovascular complications and non-alcoholic fatty liver disease seen in T2DM have been shown to begin during a prediabetic state [ 37 , 38 ]. Hence, this current study was aimed at investigating the changes in the functioning of the HPA axis in a HFHC diet-induced prediabetic rat model.…”

Hepatoprotective Effects of a Ruthenium(II) Schiff Base Complex in Rats with Diet-Induced Prediabetes

“…All chemicals and drugs were of analytical grade and purchased from standard commercial suppliers. Previous studies showed that the dose of the ruthenium complex used in this study was nontoxic 23 , 24 …”

“…We speculate that these findings may be due to the metal complex activating several key reactions, in particular those catalyzed by heme oxygenase 1, biliverdin reductase, and UDP-glucuronosyltransferase enzymes, which play an important role in bilirubin homeostasis 47 , 49 . Although we have not investigated these reactions in this study, this metal compound has been shown to have cardioprotective properties in diet-induced prediabetes rats and we speculate that these effects could be, in part, attributed to its effects on the synthesis of bilirubin in the liver 24 . Recent studies have identified bilirubin to be a major contributor to the total antioxidant capacity in blood 47 .…”

“…Ruthenium (II)-derived complex has been shown to possess anti-inflammatory properties and exhibited protective effect against lipopolysaccharide-induced liver injury in mice through mediation the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathways 22 . Furthermore, recent studies have reported that ruthenium(II) complex with a diimine uracil chelating ligand possesses antidiabetes properties that improved glycemic control, insulin sensitivity, and decreased risk of developing diabetes-related cardiovascular diseases in diet-induced prediabetic rats 23 , 24 . However, the effects of this metal complex on hepatic complications in the prediabetic state remain unknown.…”

The Dysregulation of the Hypothalamic-pituitary-adrenal Axis in Diet-induced Prediabetic Male Sprague Dawley Rats

“…However, studies indicate that complications often associated with T2DM begin during prediabetes (7). Previous studies done in our laboratory have found that micro-and macrovascular changes leading to complications such as cardiovascular complications and non-fatty liver disease seen in T2DM have been shown to begin during a prediabetic state (36,37). Hence, this current study was aimed at investigating the changes in the functioning of the HPA axis in a HFHC diet-induced prediabetic rat model.…”