research platform aiming to improve the understand-ing, monitoring and control of LPO in medicine and biomedical research. To achieve these goals more than 200 researchers from 26 European countries, USA, Japan and Canada developed an interdisciplinary network involving 49 research teams (www.irb.hr/costb35). The COST B35 Action was structured according to its scientifi c objectives in four working groups: (1) Improvement of methods for the deter-mination of LPO products; (2) Studies of the funda-mental aspects of LPO; (3) Pathological aspects of LPO; and (4) Development and validation of anti-oxidants. Researchers involved in these working groups were interacting in their research activities and the entire B35 Action was interacting with comple-mentary COST Actions and professional societies, in particular with the Society of Free Radical Research-Europe (SFRR-E), organizing joint workshops and conferences in 2008 (Berlin) and 2009 (Rome) and a COST B35/SFRR-E joint summer school on ‘ Lipid Peroxidation and Free Radical Signalling: Role in Pathophysiology ’ in Greece in 2008. Accordingly, even the fi nal conference of COST B35 Action in 2010 (Turin) is a particular attempt of promotion of research on LPO organized jointly with the Interna-tional 4-Hydroxynonenal Club, an interest group within the SFRR. This conference, denoted ‘ Lipid Peroxidation, Human Diseases and Ageing ’ , involved not only well known experts but in particular young researchers in the fi eld. Quantitatively summarized results of COST B35 Action are given in Table I, while their qualitative scientifi c highlights are described below.

The results of the COST action B35 refl ect fundamental activity principles of the COST system.

Lipid peroxidation research in Europe and the COST B35 action ‘ Lipid Peroxidation Associated Disorders ’

TILMAN GRUNE 1 , NEVEN ZARKOVIC 2 & KOSTELIDOU KALLIOPI 3

1 Associate Editor, Free Radical Research; Vice-Chair, COST B35, 2 Chair, COST B35, and 3 Offi cer, COST Domain: Biomedicine and Molecular Biosciences

Lipid peroxidation research

In the fi eld of free radical and oxidative stress research, lipid peroxidation (LPO) has been studied intensively over decades. Starting in the areas of chemistry and food chemistry, lipid peroxidation research shifted to become a hot topic in biological research. It is now widely acknowledged that LPO processes play a role in several diseases and the ageing process. This is based on the effects of LPO on cellular metabolism and cell functioning. Scientifi c research in the fi eld of LPO started from the dogma that LPO-related pro-cesses are always damaging. Current understanding of LPO is more complex and numerous modulatory effects are known which are important for maintain-ing cellular integrity and adaptive cellular responses.

The work on LPO is focused in particular on the development of analytical methods, the formation rate of various metabolites and, of course, on the suppres-sion of LPO by various antioxidants. However, research in LPO was, until recently, carried out in numerous laboratories that exchanged experience and results, but did not intensively interact and coordinate their research activities. Therefore, a joint initiative was cre-ated during the past 4 years within the European Cooperation in the fi eld of Scientifi c and Technical Research (COST), denoted COST B35 Action ‘ Lipid Peroxidation Associated Disorders: LPO ’ .

The COST initiative ‘ Lipid Peroxidation Associated Disorders ’ (COST B35 Action, 2006 – 2010)

In order to increase and disseminate the knowledge on LPO, the COST B35 Action provided a networking

Correspondence: Dr. Tilman Grune, Research Institute for Environmental Medicine (IUF), Dusseldorf, Germany

Free Radical Research, October 2010; 44(10): 1095–1097

ISSN 1071-5762 print/ISSN 1029-2470 online © 2010 Informa UK, Ltd. DOI: 10.3109/10715762.2010.504395

GUEST EDITORIAL

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1096 T. Grune et al.

The B35 Action was the fi rst European initiative coordinating research in the fi eld of LPO and oxida-tive stress. Being very successful, COST B35 Action was followed by several COST actions afterwards that interacted fruitfully and served as a base for new research and networking activities in the fi elds of oxidative stress and alterations of structure and function of major bioactive molecules, in particular molecular biosciences dealing with lipid and protein metabolism.

COST in EUROPE; the benefi ts of networking in science

So, what is COST under which COST B35 was funded? COST is an inter-governmental framework for European CO operation in S cience and T echnol-ogy (www.cost.eu). It promotes and coordinates nationally-funded research in Europe and thus con-tributes to reducing the fragmentation in European research investments, while at the same time opening the European research area to cooperation world-wide. Together with EUREKA and the EU FP pro-grammes, COST is one of the three pillars of joint European research initiatives, with COST being the oldest one (since 1971).

COST has nine scientifi c Domains (Table II), one of which is the Domain of Biomedicine and Molecu-lar Biosciences (BMBS). COST Action B35 was funded under the BMBS Domain, which currently funds a total of 29 Actions. COST is unique in that it invites multi- and inter-disciplinary proposals under the ‘ Trans-Domain ’ track; proposals scanning across different areas and thus not fi tting in a single Domain are submitted in the Trans-Domain track.

COST provides funds for research networks, called Actions, which form the main COST instrument. A COST Action is a consortium of — mainly — European scientists working on a common research area. Actions are supported for 4 years for networking and dis-semination activities, like meetings, exchange visits, publications, dissemination, training, and average funding is 100 kEuros per year per action.

COST is often criticized in that it does not fund research and that its funding is limited. Yet, COST caters for such important aspects of the research envi-ronment like networking activities, which remain either non-funded by the research grants or are bound by complex management and pre-determined par-ticipations (of the consortia members only). In con-trast, a COST action remains dynamic and allows the addition of new members throughout its life span of 4 years and is based on fl exible management and fast-track procedures acting as a catalyst to bring scientists together.

A COST action will allow a total of 8 – 10 large work-shops with 60 – 70 scientists/workshop (also from part-ners who joined after the start of the action) (on average this translates into up to 600 scientists network-ing for the lifetime of an action). The continuity of meetings with colleagues over 4 years supports in-depth discussion of scientifi c matters, creates new coopera-tions (especially with scientists who join the action after its start) and sustains pre-existing collaborations.

COST action B35 on ‘ Lipid peroxidation and asso-ciated disorders ’ , was such an example of a very suc-cessful COST Action which attracted more researchers into the fi eld, stimulated and sustained future collaboration of the members and advanced the knowledge on LPO. As a result, the current issue of Free Radical Research serves as the fi nal publication of COST B35, but again we hope that it is also a starting point for new ways in LPO research.

The COST B35 action tribute to the LPO research

The COST B35 action as networking research-initiative was well aware of the fact that development

Table I. Quantitative summary of results of the activities during the 4-year period (2006 – 2010) of COST B35 action lipid peroxidation associated disorders.

Activity/result Value

Meetings (Workshops, Conferences) 19Research and training summer schools 2Short-term scientifi c missions (exchange study visits of researchers)

41

Validation of the LPO methods/assays 3 ∗ Joint COST B35 acknowledging publications � 200

∗ Results of validation of MD (HPLC), HNE-His adducts (ELISA), F2-IsoPs (ELISA, GC/LC-MS) methods applied on human UVA-treated plasma presented by Breusing et al. [3] in this issue.

Table II. COST scientifi c domains.

Cluster of Life Sciences

BMBS, Biomedicine and Molecular BiosciencesFA, Food and AgricultureFPS, Forests, their Products and Services

Cluster of Natural Sciences

CMST, Chemistry and Molecular Sciences and TechnologiesESSEM, Earth System Science and Environmental ManagementMPNS, Materials, Physical and Nanosciences

Cluster of Science and Society

ISCH, Individuals, Societies, Cultures and HealthICT, Information and Communication TechnologiesTUD, Transport and Urban Development

Trans Domain area (not a separate Domain currently) allows for multidisciplinary proposals which cannot be submitted to a single Domain.

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Guest Editorial 1097

of LPO was always triggered by the availability of methods. This development started already with early possibilities to detect malondialdehyde (or rather thiobarbituric acid reactive substances) developed by Yagi and colleagues [1,2], and is continued today using a modern repertoire of immunochemistry and MS-based techniques. However, the detection of lipid peroxidation is still not satisfactory, especially the comparison of the results from different laboratories is far from desirable. Therefore, inter-laboratory com-parisons, standardizations of methods and distribu-tion of stabilized standards are still on the agenda of LPO research. The publication of Breusing et al. [3] describes the most recent attempt and gives some ideas about current possibilities. Interestingly, out of the standard methods the determination of thiobar-bituric acid reactive substances based on HPLC with fl uorescence detection seems to be still the most con-venient for human plasma samples used in this study [3]. Since all thiobarbituric acid-based tests have seri-ous disadvantages, the search for new methods is important for the exact evaluation of LPO related processes. As Spickett et al. [4] point out, there are two principal ways to go: (i) the use of new methods (GS-MS, ELISA-based, etc.) and (ii) the identifi ca-tion and detection of more specifi c, stable products of LPO (oxysterols, isoprostanes, etc.). Interestingly, this approach was already undertaken for the fi rst time many years ago, by analysing the complex spec-trum of fatty acid oxidation products in the early 1960s. This led to the discovery of 4-hydroxynonenal (HNE) in 1962 by Schauenstein and Esterbauer. Since then, much work has been performed to study the formation, the effects and the detoxifi cation of this compound. The focusing on HNE led to the impression that HNE is the only LPO product, but one should not forget that LPO is a complex process accompanied by oxidative degradation of many cel-lular lipids and the formation of a whole array of products. However, the effects of LPO are not limited to the ‘ pure ’ chemical formation. Numerous enzymes are able to transform LPO products, secondary metabolites are formed and some of these have a more damaging effect when compared to the original LPO products. Knowledge on the chemistry and biochemistry of LPO is summarized by Guéraud et al. [5]. Highlighting hot research topics on bio-transformation, modifi cation of macromolecules and signalling effects, this review gives an excellent overview.

Many, if not all, of these products infl uence cellular metabolism and are contributing eventually to patho-logical processes, as reviewed by Negre-Salvayre et al. [6]. Evidence is given that LPO takes part in neuro-degenerative diseases, in atherosclerosis, diabetes, cancer, infl ammatory diseases and fi nally in the

ageing process itself. Since it is well-established that over-production of LPO products will have pathological consequences, the suppression of unwanted LPO to reduce the load with LPO products is a major research fi eld. New natural and synthetic antioxidants are used to achieve the desired effects and target these compounds to their site of action. LPO is clearly not only a pathological but also a phys-iological process for various cells and tissues. There-fore, antioxidants may be considered as biological stress – response modifi ers interacting with cellular components during homeostasis and hormesis. This is reviewed by Augustyniak et al. [7].

COST B35 action ‘ Lipid peroxidation and associ-ated disorders ’ was attracting many new researchers into LPO research. Therefore, the current issue on Free Radical Research is formally the fi nal publication of COST B35 action, but it is hopefully also a starting point for new ways in LPO research and scientifi c and technological collaborations.

Declaration of interest: The authors report no con-fl icts of interest. The authors alone are responsible for the content and writing of the paper.

References

Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in [1] animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351 – 358. Yagi K. Assay for blood plasma or serum. Methods Enzymol [2] 1984;105:328 – 331. Breusing N, Grune T, Andrisic L, Atalay M, Bartosz G, Biasi [3] F, Borovic S, Bravo L, Casals I, Casillas R, Dinischiotu A, Drzewinska J, Faber H, Fauzi NM, Gajewska A, Gambini J, Gradinaru D, Kokkola T, Lojek A, Ł uczaj W, Margina D, Mascia C, Mateos R, Meinitzer A, Mitjavila MT, Mrakovcic L, Munteanu MC, Podborska M, Poli G, Sicinska P, Skrzydlewska E, Vina J, Wiswedel I, Zarkovic N, Zelzer S, Spickett CM. An interlaboratory validation of methods of lipid peroxidation measurement in UVA-treated human plasma samples. Free Radic Res 2010;44:1203–1215. Spickett CM, Wiswedel I, Siems W, Zarkovic K, Zarkovic N. [4] Advances in methods for the determination of lipid peroxida-tion products. Free Radic Res 2010;44:1172–1202 . Gu é raud F, Atalay M, Bresgen N, Cipak A, Eckl PM, Huc L, [5] Jouanin I, Siems W, Uchida K. Chemistry and biochemistry of lipid peroxidation. Free Radic Res 2010;44:1098–1124. Negre-Salvayre A, Auge N, Ayala V, Basaga H, Boada J, [6] Chapple S, Cohen G, Feher J, Grune T, Lengyel G, Mann GE, Pamplona R, Poli G, Portero-Otin M, Riahi Y, Salvayre R, Sasson S, Serrano J, Shamni O, Siems W, Siow RCM, Zarkovic K, Zarkovic N. Pathological aspects of lipid peroxi-dation. Free Radic Res 2010;44:1125–1171. Augustyniak A, Bartosz G, C[7] ˇ ipak A, Duburs G, Hor á kov á L, Ł uczaj W, Majekova M, Odysseos AD, Rackova L, Skrzydlewska E, Stefek M, Strosov á M, Tirzitis G, Venskutonis R, Viskupicova J, Vraka S, Ž arkovi c N. Natural and synthetic antioxidants for prevention of lipid peroxidation. Free Radic Res 2010;44:1216–1262.

This paper was fi rst published online on Early Online on 16 July 2010.

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