Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Geroscience ; 46(1): 795-816, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38041783

ABSTRACT

In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang-Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.


Subject(s)
Flavonols , Hydrogen Sulfide , Longevity , Phenylbutyrates , Female , Mice , Male , Animals , Meclizine/pharmacology , Hydrogen Sulfide/pharmacology , Dimethyl Fumarate/pharmacology , Mycophenolic Acid/pharmacology , Xanthophylls
2.
Am J Cardiol ; 101(10A): 58D-68D, 2008 May 22.
Article in English | MEDLINE | ID: mdl-18474276

ABSTRACT

Oxidative stress and inflammation are implicated in several different manifestations of cardiovascular disease (CVD). They are generated, in part, from the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that activate transcriptional messengers, such as nuclear factor-kappaB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Despite this connection between oxidative stress and CVD, there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, "upstream" approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. However, human clinical trials with several different well-known agents, such as vitamin E and beta-carotene, have been disappointing. Does this mean antioxidants as a class are ineffective, or rather that the "right" compound(s) have yet to be found, their mechanisms of action understood, and their appropriate targeting and dosages determined? A large class of potent naturally-occurring antioxidants exploited by nature-the oxygenated carotenoids (xanthophylls)-have demonstrated utility in their natural form but have eluded development as successful targeted therapeutic agents up to the present time. This article characterizes the mechanism by which this novel group of antioxidants function and reviews their preclinical development. Results from multiple species support the antioxidant/anti-inflammatory properties of the prototype compound, astaxanthin, establishing it as an appropriate candidate for development as a therapeutic agent for cardiovascular oxidative stress and inflammation.


Subject(s)
Antioxidants/therapeutic use , Cardiovascular Diseases/drug therapy , Inflammation/drug therapy , Oxidative Stress/drug effects , Xanthophylls/therapeutic use , Animals , Antioxidants/pharmacology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Humans , Inflammation/metabolism , Inflammation Mediators/metabolism , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism , Xanthophylls/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...