Τόμος 16 (1998) – Τεύχος 1 – Άρθρο 1 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 16 (1998) – Issue 1 – Article 1 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Από | | Άρθρο - Article, Νικόλαος Αθανασιάδης,Νicolas Athanasiadis, Πλήρες Κείμενο στα Ελληνικά - Full Text in Greek, Σταύρος Τ. Πλέσσας - Stavros T. Plessas, Στυλιανός Παπαδάκης,Stylianos Papadakis

 

Τίτλος – Title

Πο­λυα­κό­ρε­στα ω-3 Λι­πα­ρά Ο­ξέ­α και Εικοσανοειδή: Προ­έ­λευ­ση, Βιο­χη­μεί­α και Ρό­λος τους σε Φυ­σιολο­γι­κές Κα­τα­στά­σεις και σε Καρ­διαγ­γει­α­κή Νόσο. Σύγ­χρο­νη Θε­ώ­ρη­ση

ω-3 Polyunsaturated Fatty Acids and Eicosanoids: Sources, Biochemistry and Functions in Physiological Condi­tions and in Car­diovascular Disease. Current Status
Συγγραφέας – Author

Σταύρος Τ. Πλέσσας, Νικόλαος Αθανασιάδης, Στυλιανός Παπαδάκης

Εργαστήριο Φυσιολογίας, Τμήμα Νοσηλευτικής, Πανεπιστήμιο Αθηνών, Αθήνα

Stavros T. Plessas, Νicolas Athanasiadis, Stylianos Papadakis

Laboratory of Physiology, Department of Nurs­ing, University of Athens, 3 Dilou str., 115 27 Athens, Greece
Παραπομπή – Citation

Πλέσσας,Σ.Τ.,Αθανασιάδης,Ν., Παπαδάκης,Σ.  : Πο­λυα­κό­ρε­στα ω-3 Λι­πα­ρά Ο­ξέ­α και Εικοσανοειδή: Προ­έ­λευ­ση, Βιο­χη­μεί­α και Ρό­λος τους σε Φυ­σιολο­γι­κές Κα­τα­στά­σεις και σε Καρ­διαγ­γει­α­κή Νόσο. Σύγ­χρο­νη Θε­ώ­ρη­ση , Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 16 : 5-29 (1998)

Plessas,S.T., Athanasiadis,N., Papadakis,S. : ω-3 Polyunsaturated Fatty Acids and Eicosanoids: Sources, Biochemistry and Functions in Physiological Condi­tions and in Car­diovascular Disease. Current Status, Epitheorese Klin. Farmakol. Farmakokinet. 16: 5-29 (1998)
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Λέξεις κλειδιά – Keywords

ω-3 Πο­λυα­κό­ρε­στα λι­πα­ρά ο­ξέ­α (ω-3 ΠΑ­ΛΟ), α-λι­νο­λε­νι­κό ο­ξύ, ει­κο­σι-­ðå­íôá­å­íï­ú­êü ο­ξύ, ει­κο­σι­δυο-­å­îá­å­íï­úêü ο­ξύ, ε­πι­δη­μιο­λο­γί­α, αθηροσκλήρυνση και θρόμ­βω­ση στα ζώ­α, πα­ρά­γο­ντες κιν­δύ­νου καρ­διαγ­γει­α­κής νό­σου (ΚΑΝ), λι­πί­δια και λι­πο­πρω­τε­ΐ­νες πλάσματος, λει­τουρ­γί­α αι­μο­πε­τα­λί­ων, τοί­χω­μα αγ­γεί­ων, λει­τουργί­α λευ­κο­κυτ­τά­ρων, αρ­τη­ρια­κή πί­ε­ση αί­μα­τος, πή­ξη και ι­νω­δό­λυ­ση, ρε­ο­λο­γί­α, α­σθε­νείς με ΚΑΝ, α­σθε­νείς υ­ψη­λού κιν­δύ­νου για ΚΑΝ, α­σθε­νείς με υ­πε­ρλι­πι­δαι­μί­α, α­σθε­νείς με αρτηριακή υ­πέρ­τα­ση, α­σθε­νείς με σακ­χα­ρώ­δη δια­βή­τη, α­σφά­λει­α ω-3 ΠΑ­ΛΟ

ω-3 Polyunsaturated fatty acids (ω-3 PUFA), α-linolenic acid, ei­cosapen­taenoic acid, docosahexaenoic acid, epidemiology, atherosclerosis and thrombo­sis in animals, risk factors for cardiovascular disease (CVD), plasma lipids and lipoproteins, platelet function, vessel wall, leucocyte function, blood pressure, coagu­lation and fi­brinolysis, rheology, patients with CVD, patient at high risk for CVD, patients with hyper­lipidaemia, patients with hypertension, patients with dia­betes mellitus, safety of ω-3 PUFA
Λοιποί Όροι – Other Terms

Άρθρο

Article
Περίληψη – Summary

Τα ω-3 και ω-6 πο­λυα­κό­ρε­στα λι­πα­ρά ο­ξέ­α (ΠΑ­ΛΟ) εί­ναι ση­μα­ντι­κά συ­στα­τι­κά των μεμ­βρα­νών ζω­ι­κών και φυ­τι­κών κυτ­τά­ρων. Α­πό τα ω-3 ΠΑΛΟ, τα οξέα ει­κο­σι-πε­ντα­ε­νο­ϊ­κό (Ε­ΡΑ, 20:5ù-3) και ει­κο­σι­δυο-ε­ξα­ε­νο­ϊ­κό (DHA, 22:6ù-3) προ­έρ­χο­νται σχε­δόν α­πο­κλει­στι­κά α­πό θα­λάσ­σιες πη­γές. Τα ω-3 ΠΑ­ΛΟ της δια­τρο­φής εν­σωμα­τώ­νο­νται στις μεμ­βρά­νες των κυτ­τά­ρων υ­πό μορ­φή ε­στέ­ρων με φω­σφολι­πί­δια, ε­πη­ρε­άζουν ο­ρι­σμέ­να χα­ρα­κτη­ρι­στι­κά των μεμ­βρα­νών και α­πο­τε­λούν τις μη­τρι­κές ου­σί­ες για τη βιο­σύν­θε­ση βιο­λο­γι­κώς ε­νερ­γών ει­κο­σανο­ει­δών. Ου­σί­ες χρη­σι­μεύ­ου­σες ως αγ­γε­λια­φό­ροι για την πα­ρα­γω­γή ει­κο­σα­νο­ει­δών συν­δέ­ο­νται με υ­πο­δο­χείς τους στην κυτ­τα­ρι­κή μεμ­βρά­νη και ε­νερ­γο­ποι­ο­ύν φω­σφο­λι­πά­σες, οι ο­ποί­ες α­πε­λευ­θε­ρώ­νουν τα ΠΑ­ΛΟ α­πό τα φω­σφο­λι­πί­δια της μεμ­βρά­νης. Το Ε­ΡΑ με­τα­βο­λί­ζε­ται στα αι­μο­πε­τά­λια προς τη θρομ­βο­ξά­νη Α3 (ΤΧΑ3), στα λευ­κο­κύτ­τα­ρα προς το λευ­κο­τριέ­νιο Β5 (LTB5) και στα εν­δο­θη­λια­κά κύτ­τα­ρα προς την προ­στα­κυ­κλί­νη Ι3 (PGI3). Το DHA πι­θα­νώς δεν με­τα­βο­λίζε­ται στα θη­λα­στι­κά προς ου­σί­ες βιο­λο­γι­κής σπου­δαι­ό­τη­τας, ό­μως μπο­ρεί να ε­πη­ρε­ά­σει ά­με­σα κυτ­τα­ρι­κές λει­τουρ­γί­ες και να ε­πα­να­με­τα­τρα­πεί σε Ε­ΡΑ. Τα ω-3 ΠΑ­ΛΟ ε­λατ­τώ­νουν τις συ­γκε­ντρώ­σεις των τρια­κυ­λο­γλυ­κε­ρο­λών με­τά το γεύ­μα και σε νή­στεις υ­γιε­ίς, μει­ώ­νουν τη δρα­στι­κό­τη­τα των αι­μο­πε­τα­λί­ων (μεί­ω­ση συ­γκόλ­λη­σης αι­μο­πε­τα­λί­ων: α­ντα­γω­νι­σμός με­τα­ξύ α­ρα­χι­δο­νι­κού ο­ξέ­ος και Ε­ΡΑ για την κυ­κλο­ο­ξυ­γο­νά­ση κα­τα­λή­γει σε ε­λάτ­τω­ση σχη­μα­τι­σμού της θρομ­βο­ξά­νης ΤΧΑ2) και των λευ­κο­κυτ­τά­ρων (με­τα­τρο­πή του Ε­ΡΑ σε LTB5 μέ­σω της πο­ρεί­ας της λι­πο­ο­ξυ­γο­νά­σης και μεί­ω­ση σχη­μα­τι­σμού του LTB4 α­πό το α­ρα­χι­δο­νι­κό ο­ξύ), αυ­ξά­νουν την ι­κα­νό­τη­τα των ε­ρυ­θρο­κυτ­τά­ρων για αλ­λα­γή σχή­μα­τος, μπο­ρεί να ε­λατ­τώ­σουν ε­λα­φρώς την αρτηριακή πί­ε­ση του αί­μα­τος, να ε­πη­ρε­ά­σουν ευ­νο­ϊ­κά τα χα­ρα­κτη­ρι­στι­κά του τοι­χώ­μα­τος των αγ­γεί­ων και της ρε­ο­λο­γί­ας του αί­μα­τος (μεί­ω­ση ι­ξώ­δους), να ελατ­τώ­σουν την ι­νω­δό­λυ­ση, να αυ­ξή­σουν την ο­ξεί­δω­ση των λι­πο­πρω­τε­ϊ­νών και να μει­ώ­σουν την τά­ση για σχη­μα­τι­σμό θρομ­βώ­σε­ων. Πολ­λές με­λέ­τες δεί­χνουν ό­τι οι ε­πι­πτώ­σεις των ω-3 ΠΑΛΟ στα λι­πί­δια ο­ρού ε­ξαρ­τώ­νται α­πό τον τύ­πο του α­σθε­νούς και α­πό την πο­σό­τη­τα των κε­κο­ρε­σμέ­νων λι­πα­ρών ο­ξέ­ων στη δί­αι­τα. Σε α­σθε­νείς με υ­περχο­λη­στε­ρο­λαι­μί­α, πο­λύ υ­ψη­λές δό­σεις ω-3 ΠΑ­ΛΟ (άνω των 10 g/η­μέ­ρα) μπο­ρεί να μει­ώ­σουν με­τρί­ως την LDL χο­λη­στε­ρό­λη. Σε α­σθε­νείς με υ­περ­τρια­κυ­λο­γλυ­κε­ρο­λαι­μί­α η συ­μπλη­ρω­μα­τι­κή χο­ρή­γη­ση ω-3 ΠΑ­ΛΟ μει­ώ­νει τις τρια­κυ­λο­γλυ­κε­ρό­λες του πλά­σμα­τος κα­τά τρό­πο δο­σο­-ε­ξαρ­τώμε­νο. Σε α­σθε­νείς με οι­κο­γε­νή συνδυα­σμέ­νη υ­περ­λι­πι­δαι­μί­α, τα ω-3 ΠΑ­ΛΟ μει­ώ­νουν τις συ­γκε­ντρώ­σεις των τρια­κυ­λο­γλυ­κερο­λών του πλά­σμα­τος, δεν ε­πη­ρε­ά­ζουν ό­μως την LDL ή την HDL χο­λη­στε­ρό­λη. Σε α­σθε­νείς με αρτηριακή υπέρταση, τα ω-3 ΠΑ­ΛΟ ε­λατ­τώ­νουν την πί­ε­ση του αί­μα­τος κα­τά τρό­πο δο­σο­-ε­ξαρτώ­με­νο. Σε α­σθε­νείς με ιν­σου­λι­νο-ε­ξαρ­τώ­με­νο σακ­χα­ρώδη δια­βή­τη, η συ­μπλη­ρω­μα­τι­κή χο­ρή­γη­ση Ε­ΡΑ και DHA ε­πη­ρε­ά­ζει ευ­νο­ϊ­κά τις πα­ρα­τη­ρού­με­νες στα ά­το­μα αυ­τά με­τα­βο­λές στο με­τα­βο­λι­σμό των λι­πι­δί­ων, τη μει­ω­μέ­νη ι­κα­νό­τη­τα των ε­ρυ­θρο­κυτ­τά­ρων για αλ­λα­γή σχή­μα­τος, την ηυ­ξημέ­νη συ­γκόλ­λη­ση αι­μο­πε­τα­λί­ων και στην υ­ψη­λή αρτηριακή πί­ε­ση του αί­μα­τος. Σε α­σθε­νείς με μη ιν­σου­λι­νο-ε­ξαρ­τώ­με­νο σακ­χα­ρώ­δη δια­βή­τη, η χο­ρή­γη­ση ω-3 ΠΑ­ΛΟ συ­νή­θως ε­πι­δει­νώ­νει τον έ­λεγ­χο της γλυ­και­μί­ας, φαι­νό­με­νο που μπο­ρεί να εί­ναι δο­σο­-ε­ξαρ­τώ­με­νο και α­να­στρε­φό­με­νο με τη δια­κο­πή της χο­ρή­γη­σής τους. Οι δυ­νη­τι­κές α­νε­πι­θύ­μη­τες ε­νέρ­γει­ες των ω-3 ΠΑ­ΛΟ δεν πρέ­πει να α­γνο­ού­νται, αλ­λά να συνε­κτι­μού­νται με τα ευ­ερ­γε­τι­κά τους απο­τελέ­σμα­τα

The ω-3 and ω-6 polyunsaturated fatty acids (PUFA) are important components of animal and plant membranes. Amongst these PUFA, eicosapentaenoic acid (EPA, 20:3ù-3) and docosahexaenoic acid (DHA, 22:6ù-3) are nearly exclusively derived from marine sources. Dietary PUFA are incorporated into cell membranes es­terified to phospholipids, where they affect mem­brane characteristics and give rise to biologically active compounds. Compounds that serve as sig­nals for ei­cosanoids production bind to cell mem­brane re­ceptors and activate phospholipases that cleave the polyunsaturated fatty acids from cell mem­brane phospolipids. EPA is metabolised to TXA3 in platelets, LTB5 in leukocytes and PGI3 in endothelial cells. These products derived from EPA are called eicosanoids. DHA is probably not metabolised in mammalian cells to products of biological significance, but DHA may directly influ­ence cellular functions and can be retroconverted to EPA. ω-3 PUFA reduce fasting and post­prandial triglycerides, decrease the reactivity of platelets (decrease of platelet aggregation: com­petition between arachidonic acid and EPA for the cyclo-oxygenase reduce platelet formation of TXA2) and leukocyte reactivity (conversion of EPA to LTB5 through the 5-lipoxygenase path­way and decrease of LTB4 formation from arachidonic acid), increase erythrocyte deform­ability, and may slightly decrease blood pressure. ω-3 PUFA may also beneficially influence vessel wall characteris­tics and blood rheology (decrease of blood viscos­ity). Further­more, these com­pounds may impair fibrinolysis and could lead to increased oxi­dation of lipopro­teins. Many clinical studies show that the effects of ω-3 PUFA on serum lipids de­pend on the type of patient and whether the amount of saturated fatty acids in the diet is held constant. In patients with hypercholes­terolaemia very high dosages of ω-3 PUFA (above 10 g/day) may modestly decrease LDL cholesterol. Dietary ω-3 PUFA reduce plasma tri­glycerides in patients with hypertriglyceridaemia in a dose-dependent way. In patients with familial combined hyperlipi­daemia, dietary ω-3 PUFA re­duce plasma triglyc­erides, but have no effect on LDL cholesterol or HDL cholesterol. ω-3 PUFA dose-dependently lower blood pressure in hyper­tensive patients. Changes of lipid metabolism, re­duced erythrocyte deformability, increased plate­let aggregation and high blood pressure often found in subjects with diabetes mellitus are all fa­vourably influenced by the administration of EPA and DHA. In non-insu­lin-dependent patients sup­plementation with ω-3 PUFA usually worsens the glycaemic control; this may be a dose-related phenomenon and is re­versed after discontinuation of the supplementa­tion. Potential adverse effects of ω-3 PUFA must not be negleted, but should be viewed in light of their beneficial effects.

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