Elevation Of Oxidative Damage Research Articles

Melatonin as a Potential Regulator of Oxidative Stress, and Neuroinflammation: Mechanisms and Implications for the Management of Brain Injury-Induced Neurodegeneration

This review covers the preclinical and clinical literature supporting the role of melatonin in the management of brain injury-induced oxidative stress, neuroinflammation, and neurodegeneration, and reviews the past and current therapeutic strategies. Traumatic brain injury (TBI) is a neurodegenerative condition, unpredictably and potentially progressing into chronic neurodegeneration, with permanent cognitive, neurologic, and motor dysfunction, having no standard therapies. Due to its complex and multi-faceted nature, the TBI has highly heterogeneous pathophysiology, characterized by the highest mortality and disability worldwide. Mounting evidence suggests that the TBI induces oxidative and nitrosative stress, which is involved in the progression of chronic and acute neurodegenerative diseases. Defenses against such conditions are mostly dependent on the usage of antioxidant compounds, the majority of whom are ingested as nutraceuticals or as dietary supplements. A large amount of literature is available regarding the efficacy of antioxidant compounds to counteract the TBI-associated damage in animal and cellular models of the TBI and several clinical studies. Collectively, the studies have suggested that TBI induces oxidative stress, by suppressing the endogenous antioxidant system, such as nuclear factor erythroid 2–related factor-2 (Nrf-2) increasing the lipid peroxidation and elevation of oxidative damage. Moreover, elevated oxidative stress may induce neuroinflammation by activating the microglial cells, releasing and activating the inflammatory cytokines and inflammatory mediators, and energy dyshomeostasis. Thus, melatonin has shown regulatory effects against the TBI-induced autophagic dysfunction, regulation of mitogen-activated protein kinases, such as ERK, activation of the NLRP-3 inflammasome, and release of the inflammatory cytokines. The collective findings strongly suggest that melatonin may regulate TBI-induced neurodegeneration, although further studies should be conducted to better facilitate future therapeutic windows.

227 - Neuroprotective efficacy of curcumin in lead (Pb) induced inflammation and cholinergic dysfunction in mice

Curcumin from the rhizomes of Curcuma longa has many pharmacological activities including antioxidant, anti-inflammatory and cancer preventive properties. This study was designed to assess the protective effect of Curcumin against lead induced neurotoxicity. ICR mice were exposed to lead acetate (Pb) in drinking water (1%) with or without orally administrated Curcumin (100 and 200 mg/kgBW) and Vitamine E, the antioxidant positive control, once daily for 38 days. The results exhibited that Curcumin significantly protected against Pb induced learning deficit and memory loss in a concentration dependent manner, indicated by Water maze swimming test and Forced depression test. Pb induced a profound alteration of circulating Tumor necrosis factor-α (TNF-α), alteration inflammatory markers, TNF-α, COX-2 and iNOS, and elevation of oxidative damage, as evidenced by increasing lipid peroxide (malondialdehyde, MDA) levels in blood and brain tissues of mice as found in mice-treated with Vitamine E. The toxic effects of Pb may be mitigated by Curcumin and Vitamine E due to ameliorated inflammatory markers and increased expression of ChAT and AChE proteins lead to increased AChE activity in the brain compared to Pb alone, as shown by Western blot analysis. Taken together, these results suggested that Curcumin significantly alleviates Pb induced neurotoxicity, at least in part, by suppression inflammation, oxidative damage, alteration in neurotransmitter and enzyme expression (AChE and ChAT) with a reduction learning deficit and memory loss.

Pleurotus ostreatus, an edible mushroom, enhances glucose 6-phosphate dehydrogenase, ascorbate peroxidase and reduces xanthine dehydrogenase in major organs of aged rats

Context: Aging is now considered to be associated with an elevation in oxidative damage to macromolecules and enhanced levels of inflammation. Therefore, inhibition of age-related oxidative stress by natural supplement is an important study.Objectives: To investigate whether the treatment with Pleurotus ostreatus (Jacq.: Fr) Kumm, (Pleurotaceae) can ameliorate oxidative damage in aged rats.Materials and methods: Male Wistar rats were divided into three groups of six each: group 1, normal young rats; group 2, normal aged untreated rats; group 3, normal aged rats treated with P. ostreatus (200 mg/kg body wt administered intraperitoneally for 21 days). On the 22nd day, rats were sacrificed by decapitation; the liver, kidneys, heart and brain were removed from each rat for the biochemical and isozyme analyses of the antioxidant enzymes glucose 6-phosphate dehydrogenase (G6PDH), ascorbate peroxidase (Apx) and xanthine dehydrogenase (XDH).Results: An elevated activity of XDH was observed in the liver (G2:13.72 ± 4.1 versus G1: 7.57 ± 1.15; p < 0.05), kidneys (G2:101.48 ± 12.3 versus G1: 31.15 ± 1.71; p < 0.01), heart (G2: 63.21 ± 3.96 versus G1: 37.3 ± 2.70; p < 0.01) and brain (G2: 39.02 ± 3.96 versus G1: 19.84 ± 1.22; p < 0.001). The activities of G6PDH and Apx were lowered in major organs of aged untreated rats. However, treatment of P. ostreatus to aged rats resulted in decreased XDH and increased G6PDH and Apx activities in liver, kidneys, heart and brain. Interestingly, analyses of isozyme pattern of these enzymes are support the results obtained from the spectrophotometric determinations.Conclusion: These results suggest that an extract of P. ostreatus can protect the age-related oxidative damage in major organs of Wistar rats by enhancing the antioxidant enzymes G6PDH and Apx and by reducing XDH.

Abstract 19756: Association of Increased PTEN-Induced Putative Kinase 1 (PINK1) Expression and Oxidative Damage in Gastrocnemius Myofibers of Patients with Peripheral Arterial Disease

Introduction: Oxidative damage (OxD) determined as protein adducts of 4-hydroxy-2-nonenal (HNE) is increased in gastrocnemius myofibers of patients with peripheral arterial disease (PAD) and correlates with disease progression. Mitochondria in PAD gastrocnemius exhibit structural damage and respiratory dysfunction; however, the extent of mitochondrial damage and its relationship to OxD have not been determined. PINK1 is a glycoprotein normally expressed in low abundance on the mitochondrial external membrane. Mitochondrial damage signaled as loss of ion potential across the external membrane produces a marked increase in PINK1, which initiates mitophagy. In this study, we tested the hypothesis that mitochondrial damage is 1) prevalent among gastrocnemius myofibers of PAD patients and 2) linked to OxD. Methods: Gastrocnemius biopsies were collected from five PAD patients with claudication and five controls matched on the basis of age, gender, smoking history and type II diabetes. Biopsy specimens were fixed in methacarn, embedded in paraffin, sectioned and mounted to glass slides. Fluorescence labeled PINK1 protein and HNE adducts in individual myofibers, were quantified by quantitative fluorescence microscopy and expressed as mean pixel intensity in gray scale units (gsu) corrected for background. Results: PINK1 protein expression was increased (p=0.008) in PAD (mean ± S.E.M.; 494.78 ± 0.02 gsu) compared to control myofibers (102.45 ± 0.02 gsu) of the gastrocnemius. PINK1 was increased in 93% of the PAD myofibers. The association of increased (greater than two standard deviations above the control means) PINK1 expression and HNE adducts was determined for PAD myofibers. HNE adducts were increased in 67% of a random sample of PAD fibers expressing increased PINK1. Conclusions: Increased expression of PINK1 protein in the gastrocnemius myofibers of PAD patients with claudication, has established the presence of irreversible mitochondrial damage in a large proportion of myofibers. Elevation of OxD in 67% of PAD myofibers expressing increased PINK1 links OxD and mitochondrial damage. The data are consistent with a contribution of OxD to myofibers in PAD gastrocnemius, by damaged mitochondria.

The free‐radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan

Recent work on a small European cave salamander (Proteus anguinus) has revealed that it has exceptional longevity, yet it appears to have unexceptional defences against oxidative damage. This paper comes at the end of a string of other studies that are calling into question the free-radical damage theory of ageing. This theory rose to prominence in the 1990s as the dominant theory for why we age and die. Despite substantial correlative evidence to support it, studies in the last five years have raised doubts over its importance. In particular, these include studies of mice with the major antioxidant genes knocked out (both singly and in combination), which show the expected elevation in oxidative damage but no impact on lifespan. Combined, these findings raise fundamental questions over whether the free-radical damage theory remains useful for understanding the ageing process, and variation in lifespan and life histories.

Lipoprotein lipase activity and protein oxidative damage are increased in brain by age but not by fish oil ingestion

Dietary fish oil containing n-3 polyunsaturated fatty acids (PUFA n-3) plays a protective role in the prevention of cardiovascular diseases. However they may potentially produce a negative health effect because their susceptibility to free radical-induced oxidative damage. This effect would be particularly significant during aging. In order to investigate if fish oil ingestion is associated with elevation of oxidative damage in the brain, we compared in rats fed 3–4 months (young) or 18–22 months (aged), the effect of three diets: a cereal based diet (N), and a modified cereal based diet supplemented with either 10 wt % fish oil (FO) or 10 wt % coconut oil (CO). We studied the influence of these diets in the fatty acid composition, in the lipoprotein lipase (LPL) and glutamine synthetase (GS) activities, and in the concentration of protein carbonyls and reduced glutathione (GSH) of the rat brains. Results showed that FO may regulate the brain lipid composition of young and aged rats, not affecting the oxidative level of cytosolic proteins. On the other hand, brains from aged rats exhibit increased protein oxidative damage and LPL activity when compared to young rats.