Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy

Abstract

Heart failure (HF) is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ) (70 mg /kg). Riboflavin (20 mg/kg) was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV) remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD), the level of malondialdehyde (MDA) as well as heme oxygenase-1 (HO-1) protein level. Myocardial connective tissue growth factor (CTGF) level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP) rate of pressure rose (+dp/dt), and rate of pressure decay (-dp/dt) were depressed while left ventricular end-diastolic pressure (LVEDP) was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest that riboflavin treatment ameliorates myocardial function and improves heart oxidant status, whereas raising myocardial HO-1 and decreasing myocardial CTGF levels have beneficial effects on diabetic cardiomyopathy.

Keywords: diabetic cardiomyopathy; heme oxygenase-1.; riboflavin.

Figure 1

Effect of riboflavin on the level of CK and LDH in serum after treatment with riboflavin in diabetic rats. All values represent mean±SEM (n=8). **P<0.01, significant difference to control rats; ##P<0.01, significant difference to diabetic rats. CK, creatine kinase; LDH, lactate dehydrogenase.

Figure 2

Effect of riboflavin on the level of MDA (a) and SOD (b) in diabetic rats. All the values represent mean±SED (n=8). **P<0.01, significant difference to control rats; ## P<0.01, significant difference to diabetic rats. SOD, superoxide dismutase; MDA, malondialdehyde.

Figure 3

Western blot of HO-1 (a) and CTGF (b) in heart after treatment with riboflavin in diabetic rats. HO-1and CTGF were normalized with respect to actin in respective controls. Similar results were obtained in four independent sets of experiments. All the values represent mean±SEM (n=4). **P<0.01, significant difference to control rats; ##P<0.01, significant difference to diabetic rats. HO-1, heme oxygenase-1; CTGF, connective tissue growth factor.