Objective:
Metabolic syndrome (MetS), generally characterized with insulin-resistance, leads to severe cardiovascular disorders, however, the underlying mechanisms of this syndrome has not yet been fully determined. In addition, there are some controversies related with unti-diabetic agents used for treat-ment of MetS-induced complications, including their aggravating effects on the depressed cardiac function. Therefore, in this study, we first aimed to investigate the effects of pioglitazone, known as a insulin-sensitizer, on MetS-induced heart dysfunction. Second, for a comparative study to determine whether MetS-induced heart dysfunction is due to increased oxidative stress, we used a known antioxidant (querce-tin) to MetS rats for the same period.
Material and Methods:
Total 28 male Wistar rats (3 months) were grouped as control group, (Con), MetS group (MetS; added 32% sucrose to drinking water for 18-week), MetS group supplemented with pioglita-zone (Piog; 30 mg/kg/day via gavage for 2-week, from 16th-week of MetS-group) and MetS with quercetin (Quer; 75 mg/kg/day via gavage for 2-weeks from 16th-week of MetS group). All rats were fed with standard rat-diet and tap water at standard condition. At the end of experimental period, the body weights and blood glucose levels, and total oxidative status (TOS) and total antioxidant status (TAS) in serum by using special kits were measured for all animals. By using Langendorff-isolated-organ system, left ventricle pressu-re changes (LVPC) were measured in isolated hearts. The basal level of intracellular free Ca2+ ([Ca2+]i) and Ca2+ transients under electrical-situmulation (under action-potential) were measured in freshly isolated cardiomyocytes by enzymatic-method (loaded with Ca2+-sensitive fluorescence dye, Fura-2AM).
Results and Discussion:
Either pioglitazone or quercetin application have positive effects on body weight and high blood sugar levels in MetS-group rats. Additionally, both agents caused a small but significant increase on serum TAS levels (p<0.05) while they could not affect the increased serum TOS levels, signifi-cantly. Furthermore, quercetin has no significant effect on depressed LVPC levels, while pioglitazone treat-ment caused even more depression on LVPC levels (p<0.05). Nonetheless, both treatments induced signifi-cant protection against MetS-induced alterations in calculated parameters of [Ca2+]i levels and the Ca2+ transients obtained under electrical stimulation (p<0.05). Under the light of our data, such as positive effects on cellular level including parameters of [Ca2+]i changes in isolated cardiomyocytes and no similar positive effects in isolated-organ level, we can assert that these two-agents may have no effects on MetS-induced marked generation of fibrosis in the heart with high sucrose diet in rats.
Keywords: Diabetes, Antioxidants, Oxidative Stress, Insulin-Resistance, Tension, Ca2+ - Homeostasis
