Increasing tetrahydrobiopterin in cardiomyocytes adversely affects cardiac redox state and mitochondrial function independently of changes in NO production.

Tetrahydrobiopterin (BH4) represents a potential strategy for the treatment of cardiac remodeling, fibrosis and/or diastolic dysfunction. The effects of oral treatment with BH4 (Sapropterin™ or Kuvan™) are however dose-limiting with high dose negating functional improvements. Cardiomyocyte-specific overexpression of GTP cyclohydrolase I (mGCH) increases BH4 several-fold in the heart.

Mitochondria-targeted spin traps: synthesis, superoxide spin trapping, and mitochondrial uptake.

Development of reliable methods and site-specific detection of free radicals is an active area of research. Here, we describe the synthesis and radical-trapping properties of new derivatives of DEPMPO and DIPPMPO, bearing a mitochondria-targeting triphenylphosphonium cationic moiety or guanidinium cationic group. All of the spin traps prepared have been observed to efficiently trap superoxide radical anions in a cell-free system.

Human endothelial dihydrofolate reductase low activity limits vascular tetrahydrobiopterin recycling.

Tetrahydrobiopterin (BH₄) is required for NO synthesis and inhibition of superoxide release from endothelial NO synthase. Clinical trials using BH₄ to treat endothelial dysfunction have produced mixed results. Poor outcomes may be explained by the rapid systemic and cellular oxidation of BH₄.

Mitochondrial DNA variant for complex I reveals a role in diabetic cardiac remodeling.

Myocardial remodeling and dysfunction are serious complications of type 2 diabetes mellitus (T2DM). Factors controlling their development are not well established. To specifically address the role of the mitochondrial genome, we developed novel conplastic rat strains, i.

Carnitine and lipoate ameliorates lipofuscin accumulation and monoamine oxidase activity in aged rat heart.

In this study we have focused on the levels of lipofuscin, monoamine oxidase and cholesterol phospholipid ratio in the heart muscle of young, middle aged and aged rats. In parallel, we have also investigated the levels of carnitine and lipoic acid during aging. We observed an increase in lipofuscin accumulation and monoamine oxidase activity in both middle aged and aged rats.

L-carnitine and alpha-lipoic acid improve age-associated decline in mitochondrial respiratory chain activity of rat heart muscle.

The aging process is characterized by a general decline in physiological functions that affects many tissues and increases the risk of death. In the present investigation using various substrates, the respiration rate was observed in young, middle-aged, and aged rats upon administration of carnitine (300 mg/kg body weight) and lipoic acid (100 mg/kg body weight). We observed that the rate of respiration, both State 3 and respiratory control ratio, decreased significantly in aged rats after using various substrates (except succinate).

Carnitine and lipoic acid alleviates protein oxidation in heart mitochondria during aging process.

Oxidative modification alters the function of proteins and is thought to play an important role in the decline of cellular function during aging process. In the present study, we have evaluated the levels of oxidant production, protein oxidation, reduced and oxidized glutathione in young, middle aged and aged rats. The animals were divided into six groups, each group consisting of six animals each.

Credentials of Spirulina diet on stability and flux related properties on the biomineralization process during oxalate mediated renal calcification in rats.

Background: High Spirulina diet is a potential risk factor for nephrolithiasis since it has the capacity to increase urinary oxalate and uric acid level, facilitating lithogenesis. Our aim was to identify the effect of Spirulina diet during hyperoxaluric condition in Wistar albino rats.

Methods: The animals were divided into four groups: control (Gl, n=6); ethylene glycol (EG) induced (G2, n=6); EG+Spirulina (G3, n=6); Spirulina alone (G4, n=6).

Oxidative stress on mitochondrial antioxidant defense system in the aging process: role of DL-alpha-lipoic acid and L-carnitine.

Background: Oxidative damage is hypothesized to accumulate throughout the lifetime of an organism, eventually giving rise to aging. The mitochondria may be the primary cellular source and target of endogenous ROS as they are produced as a normal byproduct of the electron transport system.

Methods: Male albino Wistar rats were used in this study.