editorial lipid peroxidation products in human health and...

EditorialLipid Peroxidation Products in Human Health and Disease 2014

Kota V. Ramana,1 Sanjay Srivastava,2 and Sharad S. Singhal3

1 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA2 Environmental Cardiology, University of Louisville, Louisville, KY 40202, USA3Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute, City of Hope National Medical Center,Duarte, CA 91010, USA

Correspondence should be addressed to Kota V. Ramana; [email protected]

Received 25 August 2014; Accepted 25 August 2014; Published 14 September 2014

Copyright © 2014 Kota V. Ramana et al.This is an open access article distributed under theCreative CommonsAttribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Lipid peroxidation is a complex chain reaction process dueto the oxygen-free radicals mediated attack of cell membranelipids such as polyunsaturated fatty acids (PUFA) resultingin cell damage and dysfunction. The end products of lipidperoxidation yield a variety of highly reactive electrophilicaldehydes, which can act as endogenous danger signalsthat alter important cell signaling pathways responsiblefor disease pathogenesis. Recent studies identified potentialrole of lipid peroxidation products as markers of oxidativestress and biomarkers of human diseases. Indeed, a numberof preclinical and clinical studies suggest the involvementof lipid peroxidation products in numerous pathologicalconditions such as inflammation, atherosclerosis, diabetes,ageing, neurodegenerative diseases, and cancer.Thewealth ofknowledge we are gathering from the past decade or so willsignificantly help us to better understand the mechanismsby which lipid peroxidation products trigger pathologicalaspects and will help to identify novel potential targets forfuture therapeutic strategies.

The 2014 special issue of lipid peroxidation products inhuman health and disease compiles 16 excellent manuscripts,including clinical studies, research articles and reviews,which provides comprehensive evidence demonstrating thesignificance of lipid peroxidation products in various patho-logical conditions.

The 3 review articles of this issue discuss how lipidperoxidation products are involved in cell signaling whichleads to various pathological conditions. An excellent reviewarticle by A. Ayala et al. described in depth how lipidperoxidation-derived aldehydes such as malondialdehyde

(MDA) and 4-hydroxynonenal (HNE) are formed fromPUFA and their metabolism. Further, they described howMDA and HNE are involved in cell signaling that causeseither cell survival or cell death. At the end, they alsodiscussed various in vivo mammalian model systems usedfor investigating lipid peroxidation. The review article by E.Miller et al. described the significance of isoprostanes andneuroprostanes as biomarkers of oxidative stress in variousneurodegenerative diseases. Specifically, authors have nicelydiscussed the relationship between F2-isoprostanes and F4-neuroprostanes as biomarkers of lipid peroxidation in thepathogenesis of human neurodegenerative diseases such asmultiple sclerosis, Alzheimer’s disease, Huntington’s disease,and Creutzfeldt-Jakob disease. Joshi and Pratico in theirreview article discussed how lipid peroxidation is involvedin the pathophysiology of psychiatric diseases. Specifically,the authors have nicely described recent clinical data sup-porting the involvement of lipid peroxidation aldehydes inschizophrenia, bipolar, and other major depressive disorders.The review articles in this special issue provide widespreadinformation on the formation of lipid peroxidation-derivedaldehydes and their involvement in the neurological andpsychiatric diseases.

The research article by M. E. Soto et al. investigatesthe role of oxidative stress in various aortopathies. In thisstudy, aorta fragments from patients with systemic arte-rial hypertension, Marfan’s syndrome, Turner’s syndromeand Takayasu’s arteritis were evaluated for oxidative stressenzymes and structural and functional proteins. This studyindicates that the activities of glutathione peroxidase and

Hindawi Publishing CorporationOxidative Medicine and Cellular LongevityVolume 2014, Article ID 162414, 3 pageshttp://dx.doi.org/10.1155/2014/162414

2 Oxidative Medicine and Cellular Longevity

glutathione-S-transferase were decreased and the rate oflipid peroxidation was increased in all types aortopathies.However, activities of other oxidative and functional proteinsshowed variations depending upon the type of aortopathy. Across-sectional study by F. Moreto et al. examines the rela-tionship between plasma lipid peroxidation product MDAand metabolic syndrome in 148 free-living human subjects.Authors found interesting data that subjects with higherplasma MDA showed higher prevalence of metabolic syn-drome accompanied by higher waist circumference, highervalues of glucose, triglycerides, insulin resistance, and higherdietary sugar-intake. These studies indicate that MDA is amajor determinant of glucolipotoxic state in subjects withmetabolic syndrome.

Studies by P. Stiuso et al. report oxidant/antioxidantstatus and lipidomic profile in the serum of NASH patientsat the basal conditions and after one-year treatment withthe silibinin-based food integrator Realsil, they found thatchronic treatment with Realsil significantly changed the basalseverity of the disease as determined by NAS scores andmostimportantly decreased the serum lipid peroxidation. Thesedata indicate that lipidomic status in the serum of patientswith NASH could be a useful prognostic marker for theantioxidant therapies. In another study by S. Dziegielewska-Gesiak et al. investigated the role of lipid peroxidationproducts, plasma total antioxidant status andCu-, Zn-SODasbiomarkers of oxidative stress in elderly prediabetic subjects.Based on the data obtained from 52 elderly persons, thisstudy identified SOD-1 and TAS as initial stage biomarkersand thiobarbituric acid-reacting substances (TBARS) as laterstage biomarkers of oxidative stress in the elderly prediabet-ics.

Another study by P. Sutkowy et al. examined the influenceof exercise combined with whole-body cryotherapy on lipidperoxidation products formation in healthy kayakers. Thisstudy reports data on various oxidative stress and antiox-idative markers such as MDA, conjugated dienes, proteincarbonyls, total antioxidant capacity, vitamin E, cortisol, andtestosterone in 16 kayakers of the Polish National Team.The findings indicate that combining exercise during longertraining cycles with whole-body cryotherapy could be advan-tageous in kayakers. A multicentric research study reportedby L. M. Gomez-Olivan et al. examined the impact of invol-untary exposure of antineoplastic drugs in nurses in Mex-ican hospitals. When compared to occupationally exposednurses with control subjects who are not occupationallyexposed to antineoplastic drugs, the occupationally exposednurses show significantly increased levels of oxidative stressmarkers, including lipid peroxidation levels, protein carbonylcontent, super oxide dismutase, catalase, and glutathioneperoxidase. This study again addresses the significance oflipid peroxidation products as biomarkers of oxidative stressin antineoplastic exposed subjects.

M. Saenz-de-Viteri et al. created an interesting modelto investigate phototoxicity in the rabbits exposed to light.By using this model, they found that retinas from rabbitsexposed to light showed higher levels of lipid peroxida-tion than unexposed controls. They demonstrate that lightdamage causes an increase in the retinal oxidative stress

immediately after light exposure that decreases with timeof exposure, although, some morphological and apoptoticevents still appear days after light exposure. Buttari et al.investigated the effect of polyphenolic compound resveratrolto regulate the 7-oxo-cholesterol-triggered proinflammatorysignaling in M1 and M2 human macrophage subsets. Thesestudies demonstrate that in the M1 subset, resveratrol pre-vents the 7-oxo-choesterol-induced downregulation of CD16and the upregulation of MMP-2 extracts whereas in M2subset, resveratrol prevents the upregulation of CD14, MMP-2, MMP-9, and downregulation of endocytosis.These studiesalso indicate that regulation of NF-kB activation is themain signaling mechanism by which 7-oxo-choesterol andresveratrol mediate inflammatory effects.

S. A. Ganie et al. in their article reported the antioxidantand cytotoxic activities of Arnebia benthamii, an endangeredmedicinal plant of Kashmir Valley. By using rat liver micro-somes and human cancer cell lines, authors have shown theantioxidant potential of this plant extract. Specifically, theyhave shown that extract of Arnebia inhibits Fe2+/ascorbicacid-induced lipid peroxidation in rat liver microsomes andalso shows cytotoxic effects towards various cancer cell lines.The effect of antihypertensive drug Enalapril on oxidativestress markers and antioxidant enzymes in the kidneys ofspontaneously hypertensive rats was reported by G. Chan-dran et al. in their article. Particularly, they demonstrate thatEnalapril treatment significantly enhanced total antioxidantstatus and superoxide dismutase and decreased the TBARSlevels in the kidneys of hypertensive rats. These studiesindicate that Enalapril, besides its antihypertensive effect, alsodecreases the oxidative stress and lipid peroxidation in thehypertensive rat kidneys. In another research article by S.Ojha et al. reported the effect of Withania coagulans fruitextract on oxidative stress and inflammatory response in thekidneys of streptozotocin-induced diabetic rats. They haveshown that treatment of diabetic rats with Withania plantextract significantly decreased hyperglycemia, glutathionelevels, inflammatory cytokines such as IL-1b, IL-6, andTNF-𝛼, and subsequent renal injury. These studies indicatepotential antioxidative and anti-inflammatory actions of thisfruit extract in prevention of diabetic complications.

S. Perrone et al. in their clinical study investigated thehypothesis that neonatal supplementation of lutein in thefirst hours of life reduces neonatal oxidative stress in theimmediate postpartum period. This hypothesis was tested ina randomized, double-blinded clinical trial conducted among150 newborns by investigating the levels of total hydroper-oxides, advanced oxidation protein products, and biologicalantioxidant potential in the blood samples collected from thecord. Their findings indicate that neonatal supplementationof lutein in the first hours of life increases biological antiox-idant potential and reduce total hydroperoxides when com-pared to babies without lutein supplementation. In anotherinteresting randomized cross-over clinical study, L. D. Renzoet al. evaluated the outcome of consumption of McDonald’smeal and a Mediterranean meal without and with red winein healthy population. Red wine decreased the ox-LDL andincreased the expression of antioxidant enzymes in peopletaking McDonald’s or Mediterranean meals. These studies

Oxidative Medicine and Cellular Longevity 3

indicate the positive effect of red wine intake combined withwidely consumed meal types on oxidative and inflammatorygene expressions.

As an end note, it is obvious from the recently pub-lished studies and current special issue papers that lipidperoxidation products play a major role in human healthand disease. Lipid peroxidation products are now recognizedas biomarkers of oxidative stress and endogenous dangermediators of multiple cell signaling pathways. Although, overthe past several years, substantial research has shown thatlipid peroxidation has a crucial pathophysiological role inthe development of various human diseases, the exact natureof the significance of lipid peroxidation on cellular home-ostasis that maintain cell survival, differentiation, and deathleading to pathological consequences and their responsesto antioxidant therapies requires further detailed investi-gations. Newly developed technologies such as lipid fingerprinting/lipidomics and metabolomics are important toolsthat will help to define how the lipid peroxidation productsadapt and provide a buffer against increased oxidative stressin various pathological conditions. Therefore, the moleculesthat interrupt or neutralize the effects of lipid peroxidationproducts-mediated signaling pathways could be the nextimportant targets for future drug discovery studies.

Acknowledgments

Wewould like to thank all the authors and reviewerswho tookpart in the success of this special issue.

Kota V. RamanaSanjay SrivastavaSharad S. Singhal

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