The antioxidant butylated hydroxytoluene prevents early cholesterol-induced microcirculatory changes in rabbits.

Xiu, Ruijuan; Freyschuss, Anna; Ying, Xiaoyou; Berglund, Lars; Henriksson, Peter; Björkhem, Ingemar

doi:10.1172/jci117288

Cited by 22 publications

(6 citation statements)

References 22 publications

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“…endothelial dysfunction; shear-dependent dilation; arteriolar heterogeneity; ApoE3-Leiden HYPERCHOLESTEROLEMIA is a primary risk factor for coronary artery disease. Although atherosclerosis itself is confined to larger sized arteries, vascular changes extend into the microcirculation (18,20,33). In patients and animal models, hypercholesterolemia and atherosclerosis have been generally associated with an endothelial dysfunction of the resistance vasculature, representing a diminished bioavailability of nitric oxide (NO) as reflected by an impaired agonist-induced endotheliumdependent flow increase (3,8).…”

mentioning

confidence: 99%

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle

VanTeeffelen¹,

Constantinescu²,

Vink³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Hypercholesterolemia and atherosclerosis have been associated with changes in the microvasculature, in particular with endothelial dysfunction. In the present study, the impact of atherogenic conditions on arteriolar vasomotor control was determined. Arteriolar [second-order (2A) and third-order (3A) arterioles; diameter range: 9-37 microm] responses during reactive hyperemia (RH) were determined in cremaster muscle of anesthetized mice. C57Bl/6 mice on normal rodent chow were used as controls and high-fat/high-cholesterol (HFC)-fed C57Bl/6 and ApoE3-Leiden mice as hypercholesterolemic mice. The HFC diet resulted in time-dependent increases in plasma cholesterol and triglyceride concentrations (P < 0.001), which were more pronounced in ApoE3-Leiden mice (P < 0.001). In control mice, inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine (L-NNA) reduced baseline diameter from 17.9 +/- 1.2 to 15.9 +/- 1.3 microm (P < 0.05) and decreased the duration of RH [time to 50% (t50) of recovery: 23.3 +/- 3.6 vs. 12.5 +/- 1.3 s (P = 0.003)]. t50 was longer in 2A versus 3A arterioles (33 +/- 3 vs. 18 +/- 2 s, P < 0.001) and increased with wall shear rate at the beginning of RH in 2A arterioles only. Compared with control mice, RH duration was reduced in 2A arterioles of HFC mice (t50: 11 +/- 2 s, P < 0.001 vs. control) but not affected in 3A vessels. L-NNA did not affect baseline diameter in HFC mice and reduced t50 only in "slow" responders (t50 > or = 10 s). It is concluded that hypercholesterolemia results in an impairment of NO-mediated vasomotor control in 2A but not 3A arterioles during dynamic changes of perfusion like RH. 2A arterioles likely therefore represent the functional locus of endothelial dysfunction during atherogenic conditions.

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confidence: 99%

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle

VanTeeffelen¹,

Constantinescu²,

Vink³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…Active agents are characterized by a low anti-TMP index and a high ␣-tocopheroxyl radical-reducing ability (24). The bisphenolic probucol metabolite 3,3Ј,5,5Ј-tetra-tertbutyl-4,pr-bisphenol (H 212/43) is an effective coantioxidant ( Table 1), somewhat more active than butylated hydroxytoluene (BHT), a coantioxidant that inhibits atherosclerosis in rabbits (25,26). Compared with ␣-TOH, H 212/43 is a kinetically inferior radical scavenger that only moderately increases the 'lag-time' of LDL undergoing oxidation induced by high concentrations of Cu 2ϩ (27).…”

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confidence: 99%

Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice

et al. 1999

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Antioxidants can inhibit atherosclerosis in animals, though it is not clear whether this is due to the inhibition of aortic lipoprotein lipid (per)oxidation. Coantioxidants inhibit radical-induced, tocopherol-mediated peroxidation of lipids in lipoproteins through elimination of tocopheroxyl radical. Here we tested the effect of the bisphenolic probucol metabolite and coantioxidant H 212/43 on atherogenesis in apolipoprotein E and low density lipoprotein (LDL) receptor gene double knockout (apoE-/-;LDLr-/-) mice, and how this related to aortic lipid (per)oxidation measured by specific HPLC analyses. Dietary supplementation with H 212/43 resulted in circulating drug levels of approximately 200 microM, increased plasma total cholesterol slightly and decreased plasma and aortic alpha-tocopherol significantly relative to age-matched control mice. Treatment with H 212/43 increased the antioxidant capacity of plasma, as indicated by prolonged inhibition of peroxyl radical-induced, ex vivo lipid peroxidation. Aortic tissue from control apoE-/-;LDLr-/- mice contained lipid hydro(pero)xides and substantial atherosclerotic lesions, both of which were decreased strongly by supplementation of the animals with H 212/43. The results show that a coantioxidant effectively inhibits in vivo lipid peroxidation and atherosclerosis in apoE-/-;LDLr-/- mice, consistent with though not proving a causal relationship between aortic lipoprotein lipid oxidation and atherosclerosis in this model of the disease.

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“…The investigation of Yu et al (2012) showed the presence of butylated hydroxytouline (BHT) 47.5% and 42.22% in mycelia culture by solid media and submerged fermentation, respectively. BHT (V33) is well known for inhibition of LDL-oxidation (Xiu et al 1994), with IC 50 value of 2.1 µM . Presence of BHT in a significant amount can be reason of O. sinensis efficacy in treating hyperlipidemia and hypercholesterolemia (Jilal & Devraj 1996).…”

Section: Hepatoprotectionmentioning

confidence: 99%

Chemical Constituents of Yarsagumba (Ophiocordyceps sinensis (Berk.) Sung et al.), a Valued Traditional Himalayan Medicine

Shrestha

Park

et al. 2013

Nepal Journal of Science and Technology

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Ophiocordyceps sinensis (Berk.) Sung et al. is popularly known as Yarsagumba (winter worm summer grass) in Nepal. It is a well-known entomogenous fungus distributed in alpine nival zone of trans-Himalayas and Tibetan Plateau. Its occurrence in extreme biological niche and cohabitation with insect [Thitarodes (Hepialus)] larvae has led to unique assemblage of metabolites including proteins and nitrogenous compounds, polysaccharides, sterols, nucleosides, fatty acids and their derivatives, vitamins and inorganics. In traditional Chinese medicine, it is one of the most trusted main ingredients for several preparations of remedy from wide range of human health conditions. Several biological activities from O. sinensis have been reported that include anti-inflammatory, antioxidant, antitumor, anti-metastatic, immunomodulatory, antimicrobial, insecticidal, hypolipidaemic, hypoglycemic, anti-ageing, lipolytic, neuroprotective, renoprotective effects, etc. The chemical constituents and their pharmacological uses are reviewed here highlighting the potentiality of this highly esteemed traditional Himalayan medicine. Nepal Journal of Science and Technology Vol. 13, No. 1 (2012) 43-58 DOI: http://dx.doi.org/10.3126/njst.v13i1.7398

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The antioxidant butylated hydroxytoluene prevents early cholesterol-induced microcirculatory changes in rabbits.

Cited by 22 publications

References 22 publications

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle

Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice

Chemical Constituents of Yarsagumba (Ophiocordyceps sinensis (Berk.) Sung et al.), a Valued Traditional Himalayan Medicine

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