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

Kunitomo, Masaru; Yamaguchi, Yu; Kagota, Satomi; Otsubo, Kazumasa

doi:10.1254/jphs.fp0072365

Cited by 81 publications

(48 citation statements)

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“…We have previously found similar results with aortas of SHR-cp and suggested that the protective effects of telmisartan are linked to decreased oxidative-nitrosative stress via reduction of a component of NADPH oxidase, independently of its antihypertensive effect (18). Furthermore, long-term administration of Coenzyme Q10, a strong antioxidant, to SHR-cp has been reported to prevent both increased oxidative-nitrative stress and vascular dysfunction in mesenteric arteries (34). Taken together, continuous production of peroxynitrite formed by the reaction of NO with superoxide via angiotension II in blood vessels may lead to gradual development of functional damage in SHR-cp.…”

Section: Discussionsupporting

confidence: 68%

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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Section: Discussionsupporting

confidence: 68%

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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“…16) However, at present, many people take it as a nutritional supplement with the expectation that it will be effective in anti-aging or preventing metabolic syndrome. 17,18) There are a lot of reports stating that CoQ 10 has high anti-oxidant effects, which are useful in delaying aging of the body. 19,20) Awareness of health issues has been growing in Japan after the introduction of a system regulating "Food for Specified Health Use" (Tokuho), under which the use of "health claims" was allowed, in 1991.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Interaction between Nifedipine and Coenzyme Q10 in Rats: A New Type of Drug-Supplement Interaction

Nishimura

Fujimura

Hasegawa

et al. 2010

JOURNAL OF HEALTH SCIENCE

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We examined pharmacokinetic (PK) and pharmacodynamic (PD) interactions between coenzyme Q 10 (CoQ 10 ) and nifedipine (NFP), which is a popular medicine for treating hypertension, and elucidated possible mechanisms for the interaction between CoQ 10 and NFP in rats. The mean plasma concentrations of NFP in rats after the oral administration of NFP (1 mg/kg) with CoQ 10 (75 mg/kg) were increased over the study period and the area under the plasma concentration-time curve (AUC), showed a 1.47-fold increase compared with that of the control. Rats that received NFP with CoQ 10 showed a continuous decrease in the mean blood pressure over the study period compared with the control. There were no significant changes in the PK parameters of NFP after intravenous administration (1 mg/kg) between with and without oral CoQ 10 pretreatment, and also no significant changes in the intestinal excretion of rhodamine 123 (Rho123) or NFP between with and without CoQ 10 were found. In contrast, the portal plasma concentration of NFP after intra loop administration in the presence of CoQ 10 (75 mg/kg) showed a 1.6-fold increase in the AUC value compared with that of the control. As for physicochemical properties, the partition coefficient of NFP showed a marked increase in the presence of CoQ 10 over 10 mg/ml in the organic phase (n-hexane). From on an analysis of the absorbance spectrum, CoQ 10 showed a shift towards a longer wavelength in hydrophobic environments with NFP, suggesting that CoQ 10 reacts with NFP to form a charge-transfer complex due to a pi-cloud between them. In conclusion, it was found that CoQ 10 increases the oral bioavailability of NFP and that this interaction between NFP and CoQ 10 is not caused by metabolism via cycochrome P450 (CYP) 3A in the liver or intestine or by the inhibition of P-glycoprotein function, by the physicochemical interaction between them. Therefore, the solubility of NFP in a hydrophobic environment could be enhanced by forming a chargetransfer complex with CoQ 10 , and it is considered that NFP deviating from a charge-transfer complex may migrate to the blood circulation from the intestinal tract. This mechanism of interaction is considered a new type of drugsupplement interaction.

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“…Doring et al [23] and Schmelzer et al [24] Page 19 of 42 [53]. In another study, anti-inflammatory properties of CoQ10 on serum CRP levels of baboons have also been observed, but only when combined with vitamin E. This modification of serum CRP level was associated with an increase blood total antioxidant status [54].…”

Section: Page 16 Of 42mentioning

confidence: 93%

Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice

Sohet

Neyrinck

Pachikian

et al. 2009

Biochemical Pharmacology

150

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Please cite this article as: Sohet FM, Neyrinck AM, Pachikian BD, de Backer FC, Bindels LB, Niklowitz P, Menke T, Cani PD, Delzenne NM, Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice, Biochemical Pharmacology (2008Pharmacology ( ), doi:10.1016Pharmacology ( /j.bcp.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Aims:The aim of the study is to investigate the effect of the antioxidant coenzyme Q10 (CoQ10) on hepatic metabolic and inflammatory disorders associated with diet-induced obesity and glucose intolerance.Methods: C57bl6/j mice were fed for 8 weeks, either a control diet (CT) or a high fat diet plus 21% fructose in the drinking water (HFF). CoQ10 supplementation was performed in this later condition (HFFQ).Results HFF mice exhibit increased energy consumption, fat mass development, fasting glycemia and insulinemia and impaired glucose tolerance. HFF treatment promoted the expression of genes involved in reactive oxygen species production (NADPH oxidase), inflammation (CRP, STAMP-2) and metabolism (CPT1) in the liver. CoQ10 supplementation decreased the global hepatic mRNA expression of inflammatory and metabolic stresses markers without changing obesity and tissue lipid peroxides compared to HFF mice. HFF diets paradoxically decreased TBARS (reflecting lipid peroxides) levels in liver, muscle and adipose tissue versus CT group, an effect related to vitamin E content of the diet. Conclusion:In conclusion, HFF model promotes glucose intolerance and obesity by a mechanism independent on the level of tissue peroxides. CoQ10 tends to decrease hepatic stress gene expression, independently of any modulation of lipid peroxidation, which is classically considered as its most relevant effect.

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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

Cited by 81 publications

References 50 publications

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

Pharmacokinetic Interaction between Nifedipine and Coenzyme Q10 in Rats: A New Type of Drug-Supplement Interaction

Coenzyme Q10 supplementation lowers hepatic oxidative stress and inflammation associated with diet-induced obesity in mice

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