EDITORIAL Dietary polyunsaturated fatty acids and

EDITORIAL Dietary polyunsaturated fatty acids and peroxidative risks in sport practice. Alternatives J. R. HLERTAS, F. .T l\JATAIX, I\\. \JANAS, A. xt. BARGOSSr, ;\\. BATTINO"; From IIIc' 111,'1. Ii( .\llIrlillil! II'T!l!, /)"I',

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tissue and muscle lipoprotein lipase g roxv vc rv much in long distance runners.'

An a t h lct« undergoing a rest period s lowl , loses the changes previous!v ac­ quired L'\'L'n il, paradoxicallv, some en­ zvrncs rerna in cx t rcmc lv active for a long t irnc (~IS occur" for exnrnple for cyto­ chrome oxidase ~Ind monoamine oxidase) that might power some negative eflect s as it xvill 11L' [u rt hc r d iscussed." The linal aim of all these important changc" is the increased ene rgv produc­ tion ca pab ili tv (i.c., o:\ygL'n consumption) of muscle mitochondria. This process cou ld sirnult ancouslv lead to an increase in the extent of free radicals produced and the [ol lowing endogenous lipid pcrox ida­ rion provoking phvsico-chemical altern­ t ions of cell membrane functions with par­ ticular regard to the mitochondrial ones (disorganization of mitochondrial mem­ branes wir h subsequent modification of its Iluiditv. decrement in the efficiency of cncrgv production, structure damaging and/or aging, etc.). These topics arc of increasing world­ \\ ide interest among investigators as well as in the application of competitive train­ ing programs. However recent i nvestiga­ tions in nutrition comparing different fat sources let us inquire upon topics of rele­ vant consequence in sport practice: "Is it possible to succeed in obtaining cell mern­ branes characterized by' peculiar fatty

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acid l'(JI11!'USI t lUll and ut her p ro pcrt ie s (i.c. much rno rc rcsi s i aut tu IreL' radical insu lt) h\ means of t hc i nt ak c ol suit able f~lt sources?", This is i he rcallv main topic of the present ediroriul. A free radicul is si mp!v clclincd as am species capable 01 independent existence that con ta in s one o r more unpaired e lcc­ Irons, an unpaired clect ron being one that is a lorie in an orbital, Examples uf free radicals arc su pc rox idc (0 2 - an oxvgcn­ centered radiculj, hvd roxvl radical (HO'), The dot designates the presence of orie or more unpaired e lcct ron s. This feature makes free r~\dicals cx t rernc lv rcact ivc molecules, being capab!c 01 in t c ract ing xvi t h seve ru l organic molecules (protc ins, nucleic acids, polv unsa tu ratcd fatty acids of membrane phospholipids) and interfcr­ ing \\ ith their structure and metabolism." Sornc radicals arc sufficient lv stable to diffuse some distance in the cell, whereas others (such as HO') arc so reactive that they react with in 1 to .5 molecular di­ ameters of their site of formation, A major site of free radical production is mitochon­ drial electron transfer chain." 8 A great 102

olt ot a I O2- cc II prod uct ion comes Irom mi tochondrin and the rate of its gL'ller~ltion is direcr lvjoincd to mitochon­ drial oxvgcn consumption (7,8, for more dcra i ls seL' also previous editorial in this J OUI'll ~J1), Uncont rol lcd or elevated production of lrcc radicals is involved in long term tis­ sue inju rv, scve ra] Kinds o! cancer, im­ rnunological disorders, brain and my­ ocardial ischemia, rheumatoid arthritis, muscular dvst rophics." ') However, in the short term. the more evident result of high level lrec radical production in mitochon­ dria is a clear oxidant cllect whose main targets are the fat tv acids of membrane phospholipids, The lipid peroxidat ion process begins rupid lv with a proton ab­ straction from a mct hvl group adjacent to a cis-double bond of an unsaturated fatty acid thus producing a l at t v acid radical that could react with O 2 to produce lipid­ peroxv-radical. Later, the lipid radicals de­ veloped in the mitochondrial membrane could act ive lv react unspecificallv. Their reaction with polvunsaturated fatty acids (PUFA) may generate lipid hydroperoxide, ~\mOUIl I

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which spontaneouslv breaks down to give malondialdehyde (MDA), ethane and pen­ tane among other products (Fig 1). MDA can react with the amino group of lvsine causing the cross-linking of proteins (Fig. 2), and with other primary s-amino groups on phospholipids and nucleic acids. The lipid-pe roxv-radicals could also undergo other reactions, including cvc lizat ion ones, \\hich needs fat t v acids with two or more unsaturated bonds. It must be un­ derlined that the degradation of these cy­ clic peroxides is one of the major sources 01' MDA.IO MDA, or better ThioBarhituric Acid Rcact ive Substances (TBARS), is current lv used as a good marker or free radical product ion in biologx and medicine. Con­ seque nt lv such indicators could be fruit­ Iul!v used Cor detecting free radical gener­ ation or better their role in the induction of lipid peroxidation during intense sport­ ing practice. Lovli n et ill. 1 1 proved that plasmatic levels of MDA increase 26 0 0 in healthy ma le sportsmen that undc rwcnt exhaustive exercise, being also a pos it ive correlation with lactate levels. We recent­ h obtained similar results, as it is shown in Figure 3, with marathon runners that have also undergone an cxhaust ive exer­ cise. Taking into account that these data were referred to TBARS plasmatic values it could he supposed that the amounts of free rndica ls produced in the mitochon­ dria were much higher; mitochondrial product ion of free radicals was so high t hat the enzymatic and non-enzvrnat ic . . mechanisms by which they are usually scavenged had probably been overcome. This situation is even more evident af­ ter 30 minutes rest when TBARS values ;\IT still higher. On the other hand, it is well known that the propagation cvcle of lipid pcroxidat ion is enhanced in cell membranes because of the unsat urat ion degree of its lipids and it is reduced according to the availabil itv of the same lipids. In fact, studies in vitro showed that for each monounsaturated

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rats fed 8°0 corn oil as unique fat sc.urce: are characterized for a PUFAMCFA ratio of 4: 1 while the same ratio lowe red to 1:2 in case of solely monounsaturated dietary fat source (virg in olin.' oil), Likewise TBARS leve ls are higher in mitochondria and microsornes of rats fed CO than those Icd va (Fig. -+), so producing evidences that the degree of mcrnbrane fat tv acid en­ dogenous perox idat ion incrcases accord­ ing to t hc increment of po lvunsat u rar ion degree of d ict a rv fats. 16 On the other hand: it could be of deep interest to know if this behaviour also takes place in t hc ccl l mernbrancs of laboratory animals as \\'ell as in humans who underwent intense' sport act ivi tv peri­ ods. Therefore, wc arc actually carrving out di llc rcu t inves t igat ions in this field. However, there arc other situations which can lead to a significant endogenous production of free radicals wit h subse­ quent increase in the pcroxidat ion of phos­ pholipids' PUFA from cell mcmhranes, in this wav irid i rcc t lv monitoring the changes that might take place in athletes. An example could be the efIect induced in animals and humans by xenobiot ics ad­ ministration. Among them. Adriamvc in (ADR) is an anth rac vcl inc antibiotic that is wide lv used in cancers chcrnot herupv. ADR has been shown "in vi t ro " to initiate lipid perox idat ion. measured as TBARS production in mitochondria and micro­ somes from rat live r.!" accompanied 11\ release of PUFA,I~ a rapid accumulation of free unsatu ratcd fat tv acids, especial­ ly arachidonic acid (20:4) and docosahex­ acno ic acid (22:6), due to enhanced phos­ pholipase A 2 at tack.!? When ADR has been int rapcri toneallv administered to rats, in the last three days of 7. 8. Bc;\eris A, Ch a nc c i3 Biuchcm J 197~; 11'+;707 -16. LJ. Slam H, Hulsmann WC, Jungkind .JF, Vander k raai i AM"I, Kuster .JF. Eicosaoic]» ILJ~LJ; 21-1'+. 10. Scva ni an A, Hochrst cin P. Ann Re\ 'uli' ILJ8:;; 5;36:;90. 11. l.ovlin R, Cot tl.- W. P,kL' I, Kavanaph \1, Bclcas­ t ro A'\I. Em J Appl P\1\siol ILJ87;:;6;313-6. 12. Periauo JL, De-Lucchi C, Gil A, Suarez ;VID, Pila 1\11.. Biochelll Biophv-, AcLI lY88; Y62;f,6-72. 1~. Giron MD, Mat a i« FJ, Su.ucv I\ID . .Biochom Bi­ ophv-, All,! I LJLJO; 10'+:;:f,Y-73 1'+. Pcriauo JL. SU,Ul'/ \10, Pit o 1\11 . J Nu i r IY90; 120 986-Y'+. I:;. Leuer CL, CUl'/l'nnl'l CY, f1a,,,,\ni '\IKI, Sat'lbin P.'C1Il Nut r Did lLJ92: 278:;2-879.

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16. Hucrt as JR, Battinu 1\1, Barzant i \' C[ al . Life Sciences 1992; 50:2111-8. 17. Solaini G, Landi L. Pasquali P, Rossi CA. Bi­ orhem Biophvs Res Commun 1987: 147:573-~0. IS. Goormauht iuh E, Pollakis G, Ruvsschacrt .11\1. Biochen; Ph:lrmaco! 1983; 32;88'9-93. IY. Dernant EJF, Jensen PK. Eur J Biochern ILJ84: 132:551-8. 20. Chapman D, Wallach DFH. In: Chapman D L'd, Hio lou ica l membrane". Lundon: Acadcmic Prc"s: lLJ68: 125-202. 21. Sh ini t zk v ;VI, Inbar 1\1. Biochim Biophvs Actn 197f,; '+'3: 133-'+9. 22. Abu irmc i lch '\11\1, Elson CF.. Lipids 1980; 15:'12:;31. 23. lIuerws JR, BattillO 1\1, Mat a i x r.r. Lena> G. Bi­ oclicm Hiophvs Re" Commun ILJLJ 1; 181 :375-82. 2.+ l.cnaz G. J Membrane Biul 1'188; 10'+: ILJ3-20LJ. 25. Bever RE. Free Rad Biul &: I\kd 19'10; 8:5'+:;-6'+. 26. l luert a-, JR, Bat i ino M, l.cnn> G, Matai, FJ. FEBS L.« 1YLJI; 287:8LJY2. ,\ddl'ess rc-prin t icqucxt , tu: J. R. Hucrt a-, - l n st i lull' ul 'ull'iliun (I'\lYTAI, Dcpart m.-u t ul Phvxio]o­ g'. lni\L'I'sit\ 01 Gran,lcb - Granud«. Spain.

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