Elevated circulating levels of markers of oxidative-nitrative stress and inflammation in a genetic rat model of metabolic syndrome

Yamaguchi, Yu; Yoshikawa, Norishige; Kagota, Satomi; Nakamura, Kazuki; Haginaka, Jun; Kunitomo, Masaru

doi:10.1016/j.niox.2006.04.264

Cited by 67 publications

(61 citation statements)

References 49 publications

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“…They have been used as an animal model of MetS (16 -18). We have previously reported that oxidative and nitrative stress, together with inflammation are systemically elevated with the development of metabolic disorders characteristic to SHR / cp rats (19).…”

Section: Introductionmentioning

confidence: 95%

Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

et al. 2008

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Abstract. Metabolic syndrome (MetS) is a group of cardiovascular risk factors, including visceral obesity, glucose intolerance, hypertension, and dyslipidemia. Increased oxidative and nitrative stress and inflammation and decreased endothelial function occur in an animal model of metabolic syndrome, SHR / NDmcr-cp (SHR / cp) rats. The present study investigated the effects of coenzyme Q10 (CoQ10), one of the important antioxidants, on the abnormal oxidative condition and characteristic components of metabolic syndrome in SHR / cp rats by maintaining them on a diet supplemented with 0.07% -0.7% CoQ10 for 26 weeks. We determined serum levels of oxidatively modified low-density lipoprotein (Ox-LDL) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as oxidative stress markers, 3-nitrotyrosine as a nitrative stress marker, 3-chlorotyrosine as a marker of myeloperoxidase (MPO)-catalyzed oxidation and high-sensitivity C-reactive protein (hsCRP) as an inflammatory marker. The administration of CoQ10 significantly attenuated the increase of oxidative and nitrative stress markers and inflammatory markers in a dose-dependent manner. CoQ10 prevented the elevated serum insulin levels, although it did not affect the elevated glucose level and dyslipidemia. CoQ10 also reduced elevated blood pressure, but did not affect body weight gain. In addition, CoQ10 improved endothelial dysfunction in the mesenteric arteries. These findings suggest that the antioxidant properties of CoQ10 can be effective for ameliorating cardiovascular risk in MetS.

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Section: Introductionmentioning

confidence: 95%

Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

et al. 2008

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“…We have previously demonstrated that systemic oxidative-nitrosative stress is increased in SHR/ NDmcr-cp rats (SHR-cp), which display typical symptoms of metabolic syndrome (16), and proposed that peroxynitrite is involved in dysfunction of vasorelaxation in aortas of SHR-cp (17,18). However, it is currently unclear whether peroxynitrite is actually generated in the vascular walls per se via angiotensin II-induced NADPH-oxidase activation and contributes to dysfunction of vasodilation in SHR-cp.…”

Section: Introductionmentioning

confidence: 99%

Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome

et al. 2009

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Abstract. We have previously reported that peroxynitrite is involved in dysfunction of nitric oxide (NO)-mediated vasorelaxation in SHR/NDmcr-cp rats (SHR-cp), which display typical symptoms of metabolic syndrome. This study investigated whether peroxynitrite is actually generated in the vascular wall with angiotensin II-induced NADPH-oxidase activation, thus contributing to the dysfunction. In isolated mesenteric arteries of male 18-week-old SHR-cp, relaxations in response to acetylcholine and sodium nitroprusside were impaired compared with that in Wistar-Kyoto rats. This impaired relaxation was not restored by treatment with apocynin, an NADPH-oxidase inhibitor. Protein expression of endothelial NO synthase increased while that of soluble guanylyl cyclase (sGC) decreased in the artery. We observed increased production of superoxide anions and peroxynitrite from the artery and their inhibition by apocynin, and also increased contents of nitrotyrosine, a biomarker of peroxynitrite, in mesenteric arteries and angiotensin II in aortas. Long-term (8 weeks) administration of telmisartan, an angiotensin II type 1-receptor antagonist, prevented the impaired vasorelaxation, decreased sGC expression and increased nitrotyrosine content in mesenteric arteries. These findings suggest that in the vascular wall of SHR-cp, peroxynitrite is continually produced by the reaction of NO with NADPH oxidase-derived superoxide via angiotensin II and gradually denatures sGC protein, leading to vasorelaxation dysfunction.

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“…This statement is supported by the fact that NO is consumed in a reaction with superoxide anion yielding a strong oxidant species, ONOO -, which in turn accelerates the lipid peroxidation reaction (15,21,22). Peroxynitrite production is also supported by the elevated levels of nitrotyrosine, a marker of endogenous peroxynitrite generation found in both human and animal models (23,24). An increased concentration of uric acid may also contribute to the reduced NO, increased oxidative stress and impaired endothelial function found in the present study (20,25), leading to increased risk factors for the development of obesity, hypertension, and cardiovascular disease, which have been associated with oxidative stress (26).…”

Section: Discussionmentioning

confidence: 97%

Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress

Simão¹,

Lozovoy²,

Simão³

et al. 2011

Braz J Med Biol Res

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Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman’s rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism

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Elevated circulating levels of markers of oxidative-nitrative stress and inflammation in a genetic rat model of metabolic syndrome

Cited by 67 publications

References 49 publications

Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

Beneficial Effect of Coenzyme Q10 on Increased Oxidative and Nitrative Stress and Inflammation and Individual Metabolic Components Developing in a Rat Model of Metabolic Syndrome

Chronic Production of Peroxynitrite in the Vascular Wall Impairs Vasorelaxation Function in SHR/NDmcr-cp Rats, an Animal Model of Metabolic Syndrome

Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress

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