Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration.

The caveolin-1 scaffolding domain (CSD, amino acids 82-101 of caveolin-1) has been shown to suppress bleomycin-induced lung and skin fibrosis and angiotensin II (AngII)-induced myocardial fibrosis. To identify active subregions within CSD, we split its sequence into three slightly overlapping 8-amino acid subregions (82-89, 88-95, and 94-101). Interestingly, all three peptides showed activity.

The Caveolin-1 Scaffolding Domain Peptide Reverses Aging-Associated Deleterious Changes in Multiple Organs.

Aging is a progressive, multifactorial, degenerative process in which deleterious changes occur in the biochemistry and function of organs. We showed that angiotensin II (AngII)-induced pathologies in the heart and kidney of young (3-month-old) mice are suppressed by the caveolin-1 scaffolding domain (CSD) peptide. Because AngII mediates many aging-associated changes, we explored whether CSD could reverse pre-existing pathologies and improve organ function in aged mice.

Suppression of angiotensin II-induced pathological changes in heart and kidney by the caveolin-1 scaffolding domain peptide.

Dysregulation of the renin-angiotensin system leads to systemic hypertension and maladaptive fibrosis in various organs. We showed recently that myocardial fibrosis and the loss of cardiac function in mice with transverse aortic constriction (TAC) could be averted by treatment with the caveolin-1 scaffolding domain (CSD) peptide. Here, we used angiotensin II (AngII) infusion (2.

Bromelain-induced apoptosis in GI-101A breast cancer cells.

Bromelain is a proteolytic enzyme extracted from the stems and the immature fruits of pineapple that was found to be antitumorigenic in different in vitro models. Bromelain has been reported to promote apoptosis, particularly in breast cancer cells, with the up-regulation of c-Jun N-terminal kinase and p38 kinase. Our study was designed to determine if bromelain could induce apoptosis in GI-101A breast cancer cells.

Site-specific microtubule-associated protein 4 dephosphorylation causes microtubule network densification in pressure overload cardiac hypertrophy.

In severe pressure overload-induced cardiac hypertrophy, a dense, stabilized microtubule network forms that interferes with cardiocyte contraction and microtubule-based transport. This is associated with persistent transcriptional up-regulation of cardiac alpha- and beta-tubulin and microtubule-stabilizing microtubule-associated protein 4 (MAP4). There is also extensive microtubule decoration by MAP4, suggesting greater MAP4 affinity for microtubules.

Modulatory role of glutathione monoester in augmenting age-associated neuronal antioxidant system.

An ever-increasing number of reports show the involvement of free radicals in the functional and structural changes occurring in the brain as a part of the normal aging process. This study aimed to assess the potential efficacy of glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on memory and the antioxidant defense system and lipid peroxidation in discrete brain regions such as cortex, striatum, and hippocampus of young and aged rats. Age-associated decline in memory and activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione, vitamin E, and vitamin C, and elevated levels of lipid peroxidation and oxidized glutathione, were observed in all the brain regions studied (p < .

Age-associated alterations of lipofuscin, membrane-bound ATPases and intracellular calcium in cortex, striatum and hippocampus of rat brain: protective role of glutathione monoester.

Brain aging has become an area of intense research and a subject of much speculation fueled largely from the widely recognized fact that age is the biggest risk factor in most neurodegenerative diseases and age-related increase of reactive oxygen species is particularly detrimental to postmitotic tissues. In the present study, we have evaluated the possible role of glutathione monoester (GME), when administered intraperitoneally (12mg/kg body weight) for 20 days on age-associated changes in the levels of lipofuscin, Na+K+, Mg2+, Ca2+ ATPase activities and intracellular calcium levels in discrete brain regions of young and aged male albino Wistar rats. An age-associated increase in lipofuscin, intracellular calcium in cortex, striatum and hippocampus was observed and contradictorily, a decrease in the activities of membrane-bound enzyme activities was also observed.

Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: role of carnitine and lipoic acid.

Mitochondrial dysfunction has been implicated in the regulation of myofiber loss during aging, possibly by apoptotic pathways. However, the mitochondrial-mediated pathway of apoptosis by cytochrome c in skeletal muscle remains ambiguous. To understand this, we have studied the upstream and downstream events of cytochrome c release, and assessed the efficacy of carnitine and lipoic acid cosupplementation.

Age-associated oxidative macromolecular damages in rat brain regions: role of glutathione monoester.

The generation of reactive oxygen species (ROS) and resultant oxidative stress has been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases. We have evaluated the efficacy of glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on glutathione, ROS, superoxide anion production, lipid peroxidation (LPO), protein carbonyls, thiol status, oxidative DNA damage products such as 8-hydroxy deoxy guanosine and DNA protein cross-links in discrete brain regions of young and aged rats. An age associated increase in ROS, superoxide anion production, LPO, protein oxidation, and DNA damage products in cortex, striatum, and hippocampus was observed which was reversed by GME.

Cytochrome c oxidase rather than cytochrome c is a major determinant of mitochondrial respiratory capacity in skeletal muscle of aged rats: role of carnitine and lipoic acid.

The release of mitochondrial cytochrome c followed by activation of caspase cascade has been reported with aging in various tissues, whereas little is known about the caspase-independent pathway involved in mitochondrial dysfunction. To determine the functional impact of cytochrome c loss on mitochondrial respiratory capacity, we monitored NADH redox transitions and oxygen consumption in isolated skeletal muscle mitochondria of 4- and 24-month-old rats in the presence and absence of exogenous cytochrome c; and assessed the efficacy of cosupplementation of carnitine and lipoic acid on age-related alteration in mitochondrial respiration. The loss of mitochondrial cytochrome c with age was accompanied with alteration in respiratory transition, which in turn was not rescued by exogenous addition of cytochrome c to isolated mitochondria.

Enzymatic and non-enzymatic antioxidant status in stage (III) human oral squamous cell carcinoma and treated with radical radio therapy: influence of selenium supplementation.

Background: Oxidative stress is implicated in oral carcinogenesis and has been found to be aggravated during radiotherapy. A great deal of attention has been focused on the possible therapeutic implications of selenium as a potent antioxidant. We determined whether selenium supplementation to radiation treated oral cancer patients render improvement in the antioxidant status against oxidative stress.

Protective efficacy of alpha-lipoic acid on acetylcholinesterase activity in aged rat brain regions.

The purpose of the present investigation was to measure the activity of acetylcholinesterase in discrete regions of young and aged rat brain before and after DL-alpha-lipoic acid supplementation. Two groups of male albino rats were used in this study (4 and 24 months of age). DL-alpha-lipoic acid was administered intraperitoneally with a regimen of 100 mg/kg body weight per day using alkaline saline as a vehicle for 7 and 14 days.

Emerging role of Centella asiatica in improving age-related neurological antioxidant status.

Free radicals have been hypothesized to play an important role in ageing process. There exists an imbalance between free radical production and antioxidant defense mechanism, which may lead to cell death during ageing. Our study was designed to determine whether extract of Centella asiatica, an antioxidant, when administered orally (300 mg/kg body weight/day) for 60 days would prevent age-related changes in antioxidant defense system, lipid peroxidation (LPO) and protein carbonyl (PCO) content in rat brain regions such as cortex, hypothalamus, striatum, cerebellum and hippocampus.

Combined efficacies of DL-alpha-lipoic acid and meso 2,3 dimercaptosuccinic acid against arsenic induced toxicity in antioxidant systems of rats.

Health hazards caused by heavy metals have become a great concern to the population. Arsenic as an environmental agent is considered to be a toxic substance due to its carcinogenic potential in humans. Since arsenic compounds might exert their toxicity by the generation of reactive oxygen species, we have evaluated the effect of both DL-alpha-lipoic acid (LA) and meso 2,3 dimercapto succinic acid (DMSA) on the antioxidants and lipid peroxidation in arsenic treated rats.

Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid.

The purpose of this study was to examine the effects of DL: -alpha-lipoic acid (LA) on arsenic (As) induced alteration of glutathione (GSH) level and of the activity of glutathione-related enzymes-glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH)-in rat brain regions (cortex, hypothalamus, striatum, cerebellum and hippocampus). Male Wistar rats of 150+/-10 g weight were divided into four groups: control and three experimental groups supplemented with arsenic (sodium arsenite) alone (100 ppm mixed in drinking water), lipoic acid alone (70 mg kg(-1) body weight), arsenic plus lipoic acid (100 ppm arsenic in drinking water plus 70 mg lipoic acid kg(-1) body weight). The arsenic content of brain regions was found to increase with the administration of sodium arsenite.

Protein oxidative damage in arsenic induced rat brain: influence of DL-alpha-lipoic acid.

A body of evidence has accumulated implicating free radical generation and reaction of arsenic with protein thiols in the biochemical and molecular mechanisms of arsenic toxicity. Brain readily undergoes oxidative damage, so it is important to determine whether arsenic-induced changes in rat brain may be associated with oxidative events. An increase in oxidative stress may contribute to the development of protein damage in rat brain.

Age-associated decreased activities of mitochondrial electron transport chain complexes in heart and skeletal muscle: role of L-carnitine.

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-Carnitine (4-N-trimethylammonium-3-hydroxybutric acid) plays an important role in transport of fatty acid from cytoplasm to mitochondria for energy production. Previous studies in our laboratory reported L-carnitine as a free radical scavenger in aged rats.

Ascorbic acid and alpha-tocopherol as potent modulators on arsenic induced toxicity in mitochondria.

Arsenic exists ubiquitously in our environment and various forms of arsenic circulate in air, water, soil and living organisms. Since arsenic compounds have shown to exert their toxicity chiefly by generating reactive oxygen species, we have evaluated the effect of antioxidants ascorbic acid and alpha-tocopherol on lipid peroxidation, antioxidants and mitochondrial enzymes in liver and kidney of arsenic exposed rats. A significant increase in the level of lipid peroxidation and decrease in the levels of antioxidants and in the activities of mitochondrial enzymes were observed in arsenic intoxicated rats.

Effects of levocarnitine on mitochondrial antioxidant systems and oxidative stress in aged rats.

Objective: Levocarnitine is important in beta-oxidation of fatty acids. We evaluated the role of levocarnitine in the skeletal muscle mitochondrial antioxidant system of aged rats.

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

Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and protein oxidation in various brain regions of aged rats.

Free radicals have been implicated in the development of many acute and chronic diseases and in conditions involving brain or neurological tissue. The primary genetic material is subjected to damage by endogenous and exogenous agents, which may lead to instability and transcriptional infidelity. In the present study, we evaluated the protective effect of DL-alpha-lipoic acid, a metabolic antioxidant on lipid peroxidation, protein carbonyl content in various brain regions of aged rats when compared to brain regions of young rats.