ABSTRACT
Activation of nuclear factor-κB (NF-κB) by increased production of reactive oxygen species (ROS) might induce transcription and expression of different antioxidant enzymes and also of nitric oxide synthase (NOS) isoforms. Thus, we aimed at studying the effect of NF-κB inhibition, caused by JSH-23 (4-methyl-N (1)-(3-phenyl-propyl)-benzene-1,2-diamine) injection, on ROS and NO generation in hereditary hypertriglyceridemic (HTG) rats. 12-week-old, male Wistar and HTG rats were treated with JSH-23 (bolus, 10 µmol, i.v.). After one week, blood pressure (BP), superoxide dismutase (SOD) activity, SOD1, endothelial NOS (eNOS), and NF-κB (p65) protein expressions were higher in the heart of HTG rats compared to control rats. On the other hand, NOS activity was decreased. In HTG rats, JSH-23 treatment increased BP and heart conjugated dienes (CD) concentration (measured as the marker of tissue oxidative damage). Concomitantly, SOD activity together with SOD1 expression was decreased, while NOS activity and eNOS protein expression were increased significantly. In conclusion, NF-κB inhibition in HTG rats led to decreased ROS degradation by SOD followed by increased oxidative damage in the heart and BP elevation. In these conditions, increased NO generation may represent rather a counterregulatory mechanism activated by ROS. Nevertheless, this mechanism was not sufficient enough to compensate BP increase in HTG rats.
Subject(s)
Myocardium/metabolism , Transcription Factor RelA/metabolism , Animals , Blood Pressure/drug effects , Body Weight/drug effects , Gene Expression/drug effects , Glutathione/analysis , Heart Ventricles/metabolism , Hyperlipoproteinemia Type IV/pathology , Hyperlipoproteinemia Type IV/veterinary , Male , Nitric Oxide/metabolism , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/metabolism , Oxidative Stress/drug effects , Phenylenediamines/pharmacology , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Transcription Factor RelA/geneticsABSTRACT
Male Sprague-Dawley IVA-SIV rats were compared to male Sprague-Dawley Charles River rats of the same age, body weight, and daily food intake. The IVA-SIV rats demonstrated hypertriglyceridemia (182 +/- 9.4 v 131 +/- 9.4 mg/dL, P less than 0.001), associated with increased fasting plasma glucose (115 +/- 3 v 84 +/- 2 mg/dL, P less than 0.001), and plasma insulin (35 +/- 5 v 19 +/- 2 microU/mL, P less than 0.001) levels. Furthermore, IVA-SIV rats responded to an oral glucose load with higher plasma glucose and insulin levels. Very-low-density lipoprotein (VLDL)-triglyceride (TG) turnover studies were performed, documenting a higher TG production rate, which correlated with the plasma TG concentrations, (r = 0.58, P less than 0.01) in the IVA-SIV rats. Since lipoprotein lipase activity in both adipose tissue and muscle was not significantly different in the two groups of rats, it appears that the hypertriglyceridemia in IVA-SIV rats is due to increased VLDL-TG secretion, associated with hyperglycemia, hyperinsulinemia, and increased plasma FFA levels. The IVA-SIV rats provide a model of endogenous hypertriglyceridemia, independent of obesity.
Subject(s)
Hyperlipoproteinemia Type IV/veterinary , Rats, Inbred Strains/blood , Adipose Tissue/enzymology , Animals , Blood Glucose/metabolism , Body Weight , Disease Models, Animal , Fatty Acids, Nonesterified/blood , Hyperlipoproteinemia Type IV/blood , Insulin/blood , Lipoprotein Lipase/metabolism , Lipoproteins, VLDL/blood , Male , Muscles/enzymology , Rats , Rodent Diseases/blood , Species Specificity , Triglycerides/bloodABSTRACT
Sprague-Dawley male rats from the Ivanovas-Sieve colony (IVA-SIV) show higher plasma triglyceride levels compared to the standard Charles River (CR) rats. The triglyceride enrichment occurs primarily in the very-low-density lipoproteins (VLDL), otherwise of a normal % composition, suggesting that the number of particles is increased, rather than their triglyceride (TG) content. High-density lipoprotein (HDL) particles, corresponding to HDL1, appear to be increased in the IVA-SIV rats, as confirmed by rate-zonal ultracentrifugation. The apoprotein composition of isolated lipoproteins (apo B content and isoelectric focusing pattern), does not differ in the two strains. The IVA-SIV rats are remarkably more TG inducible, compared to the standard CR. This can be shown with fructose loading and with a cholesterol-cholic acid diet. The plasma TG increase, after Triton administration, indicative of the VLDL-TG production, is fourfold higher in the IVA-SIV, compared to the CR rats. These findings provide evidence for some similarities between the IVA-SIV rat and human endogenous hypertriglyceridemia, and suggest an increased TG biosynthesis in this model.
