Natural substance rutin versus standard drug atorvastatin in a treatment of metabolic syndrome-like condition.

BACKGROUND: Metabolic syndrome is a cluster of metabolic risk factors. The clear causes of its development are not known yet and there is no comprehensive treatment of this disease. There is a trend to use natural substances in the treatment of various diseases, but their effects need to be well explored. We decided to test effect of rutin compared to the effect of the standard drug atorvastatin. METHODS: As a model of metabolic syndrome we used males of hypertriacylglycerolemic rats in combination with high-fat-high-fructose diet. Rutin (100 mg/kg) and atorvastatin (50 mg/kg) were administered orally daily for 5 weeks. RESULTS: We determined biochemical parameters from blood: HDL-cholesterol, LDL-cholesterol, total cholesterol, triacylglycerols. Relaxation and contraction response of aorta was measured to determine vessel dysfunctions and possible predisposition to cardiovascular disease. The negative influence on cognitive functions could be associated with the development of metabolic cognitive syndrome. Therefore we aimed to monitor spatial memory by Morris water maze test. Both rutin and atorvastatin had a tendency to decrease levels of serum triacylglycerols, but only atorvastatin significantly reduced levels od LDL-cholesterol and increased HDL-cholesterol levels. Both compounds significantly reduced the phenylephrine-induced contractile response of the aorta and improved the relaxation response. Further, treated animals learned better compared to untreated rats in the Morris water maze. CONCLUSION: Based on our results we can assume that atorvastatin and rutin had positive effect on spatial memory and vessel reactivity. Atorvastatin optimized lipid profile of blood serum.

Rosmarinic acid administration attenuates diabetes-induced vascular dysfunction of the rat aorta.

OBJECTIVES: Oxidative stress as well as inflammation processes are engaged in diabetic vascular complications. Rosmarinic acid, a natural phenol antioxidant carboxylic acid, was found to have multiple biological activity, including anti-inflammatory and antitumour effects, which are a consequence of its inhibition of the inflammatory processes and of reactive oxygen species scavenging. The aim of this work was to study effects of rosmarinic acid administration on vascular impairment induced by experimental diabetes in rats. METHODS: Diabetes was induced by streptozocin (3 × 30 mg/kg daily, i.p.) in Wistar rats. Rosmarinic acid was administered orally (50 mg/kg daily). Ten weeks after streptozocin administration, the aorta was excised for functional studies, evaluation by electron microscopy and real time PCR analysis. KEY FINDINGS: In the aorta of diabetic rats, decreased endothelium-dependent relaxation was accompanied by overexpression of interleukin-1ß, tumour necrosis factor-α, preproendothelin-1 and endothelin converting enzyme-1. Structural alterations in the endothelium, detected by electron microscopy, indicated aortic dysfunction caused by diabetes. The diabetes-induced aortic disorders were prevented by rosmarinic acid administration. CONCLUSIONS: Rosmarinic acid protected aortic endothelial function and ultrastructure against diabetes-induced damage. Both antioxidant and anti-inflammatory effects of rosmarinic acid seemed to participate in the mechanism of this protection.

Effects of sesame oil in the model of adjuvant arthritis.

OBJECTIVES: The goal of this study was to evaluate the effect of sesame oil on functional damage induced by adjuvant arthritis (AA) and on changes of selected biochemical parameters reflecting oxidative tissue injury. DESIGN: Mycobacterium butyricum in incomplete Freund's adjuvans was intradermally administered to Lewis male rats. Hind paw edema and endothelium-dependent relaxation of the aorta were determined on day 28. Further, plasmatic levels of TBARS, gamma-glutamyltransferase (GGT) activity in the joint and spleen tissues, level of protein carbonyls and total antioxidant capacity (TAC) in plasma, as well as activity of the lysosomal enzyme N-acetyl-glucosaminidase (NAGA) in serum were assessed. The effect of sesame oil (SO, 1ml/kg, daily oral administration) was evaluated on day 28. RESULTS: The beneficial effect of sesame oil on markers of oxidative stress accompanying AA was demonstrated by decrease of plasma TBARS and decrease of GGT activity in the joint and spleen tissues. Level of protein carbonyls, TAC in plasma and activity of NAGA in serum and in the kidney were improved, yet not significantly. In the hind paw edema the maximal increase was found on day 28 of AA, and in the same time we observed a significant decrease of aortic endothelium-dependent relaxation. Administration of SO resulted in mild, non-significant decrease of hind paw swelling and in significantly increased acetylcholine-evoked relaxation. CONCLUSION: We conclude that SO has beneficial effects on oxidative stress induced biochemical changes occurring in AA, moreover it improves endothelium-dependent relaxation of the aorta and tends to decrease hind paw edema.

Role of inflammatory cytokines and chemoattractants in the rat model of streptozotocin-induced diabetic heart failure.

OBJECTIVE: It is not yet clear how oxidative stress, free radicals, inflammatory cytokines and chemoattractants produced in the heart induce chronic heart failure. The myocardial damage caused by chronic diabetes results either from the persistence of inflammatory signaling directly in the heart or from the dysregulation of anti-inflammatory signaling systems. In the rat model of streptozotocin-induced diabetes (STZD) we investigated 1/ the concentration of free radicals (FR), 2/ reduced glutathione (GSH), 3/ lysozomal enzymes, 4/ inflammatory cytokines (tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6)), and monocyte chemoattractant protein-1 (mcp-1) in the myocardium. METHODS: Diabetes was induced in 12 male Wistar rats by injection of streptozotocin (STZ). The free radical scavenger and cardiac protectant SMe1EC2 (10 mg/kg/d.) was given orally for 5 days and 5 weeks and these animals were compared with the diabetic and non-diabetic controls. RESULTS: We found reduced heart rate and rate dependent functions of the rat heart, early release of free radicals triggering the release of cytotoxic inflammatory cytokines (like TNF-? and IL-6) and chemoattractants (mcp-1) as an example of this type of pathogens, resulting in the initiation and progression of cardiac pathology. The reduced myocardial contractility after STZD was accompanied with the increased reactive responsiveness of isolated aorta and mesenteric artery to phenylephrine, with increased production of chemoattractive proteins directly in the myocardium, with increased activity of peripheral beta-N-acetyl-glucosaminidase (NAGA), as representative of lysosomal activation processes. The pretreatment of SME1EC2 reduced increase in vascular reactivity, reduced myocardial depression and protected against myocardial toxicity. CONCLUSION: The newly identified and specific cardiac protectant SMe1EC2 could serve as a prospective target in the treatment of increased myocardial cytokine and chemoattractive proteins in diabetic cardiomyopathy.

Cardiovascular toxicity of the first line cancer chemotherapeutic agents: doxorubicin, cyclophosphamide, streptozotocin and bevacizumab.

OBJECTIVES: Although the mechanisms responsible for the occurrence of congestive heart failure after anti-cancer therapy are largely unknown, both the formation of free radicals in the myocardium and inflammatory cytokines with resultant production of neurohormones could be operative. The common manifestations of cardiovascular toxicity after anti-cancer therapy may include cardiac ischemia, ST-segment elevation, or depression, serious hypotension and bradyarrhythmias with resultant cardiac depression and congestive heart failure, or hyper-tension, serious ventricular tachycardia, cardiac edema, QT prolongation and thrombo-embolism. METHODS & RESULTS: The mechanisms of cardiotoxicity of four representative anti-cancer agents 1) anthracycline doxorubicin, 2) and 3) alkylating agents cyclophosphamine and streptozotocin and 4) the new humanized monoclonal antibody bevacizumab (directed solely against myocardial and vascular endothelial growth factors), were investigated in chronic experiments on rodents for the occurrence and intensity of early electrocardiographic signs of cardiotoxicity, for late biochemical markers, and for the late production of congestive heart failure. Our results suggested a sneaking ascension of long-term multifactorial cardiotoxicity of the four anti-cancer agents tested. Of these quasi-selective bevacizumab (Avastin) that binds to and inhibits endothelial growth factor and thus neoangiogenicity in rats showed unexpectedly high overexpression of inflammatory cytokines and monocyte chemoattractant protein (mcp-1), both in plasma and in the myocardium. CONCLUSIONS: Thus, suddenly increased and coincidental expression of inflammatory cytokines, neurohormones and chemoattractants in plasma during anti-cancer therapy could be the long-awaited markers of imminent cardiotoxicity.