ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of curcumin on nitric oxide (NO) in plasma of atherosclerotic rabbits, activity of constitutive nitric oxide synthase (cNOS) and asymmetric dimethylarginine (ADMA), and discuss curcumin's effect against AS and its correlation with ADMA.</p><p><b>METHOD</b>Thirty-eight male Japanese white rabbits were randomly divided into four groups: the control group (eight rabbits fed with standard diets), the model group (ten rabbits fed with high-fat diets), the low dose curcumin group (ten rabbits fed with high-fat diets and 100 mg . kg-1 d -1 ) and the high dose curcumin group (ten rabbits fed with high-fat diets and 200 mg kg-1 d-1 curcumin). At the end of the 12th week, their plasmas were tested for TC, LDL-C, NO, endothelin (ET) , ADMA and activity of aortic cNOS. Aortic tissues were collected for histological examinations.</p><p><b>RESULT</b>The three groups fed with high-fat diets showed higher plasma ADMA and ET than the control group (P <0. 01) , but with decrease in plasma NO concentration and arterial cNOS activity (P <0. 01). Compared with the model group (P <0. 05) , the curcumin groups showed lower plasma ADMA and ET (P <0. 05), but higher plasma NO concentration and arterial cNOS activity than the model group (P <0. 01). There was no significant difference between the two curcumin groups.</p><p><b>CONCLUSION</b>Curcumin may play an important protective role in AS process by reducing plasma ADMA level. [Key words] atherosclerosis; asymmetric dimethylarginine; crucumin; nitric oxide; nitric oxide synthase</p>
Subject(s)
Animals , Male , Rabbits , Arginine , Blood , Atherosclerosis , Blood , Drug Therapy , Metabolism , Curcumin , Therapeutic Uses , Endothelium, Vascular , Nitric Oxide Synthase , MetabolismABSTRACT
<p><b>BACKGROUND</b>Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6).</p><p><b>METHODS</b>Twenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet beta cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Significant elevation in serum glucose levels was observed one month and six months after STZ induction (P < 0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet beta cells, while in pancreas of diabetic minipigs islet beta cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-alpha level in aotic intima conditioned medium, and significant elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR.</p><p><b>CONCLUSIONS</b>The present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) significantly elevated in aortic intima of diabetic minipigs.</p>