Palmitoylethanolamide as antioxidant and for tissue protection

N-Acylethanolamines (NAEs) (fatty acid ethanolamides) are naturally occurring hydrophobic molecules usually present in a very small amount in many mammalian tissues and cells [1] and [2]. Moreover, NAEs are normally present in biological fluids, such as blood [2], in very low concentrations. The physiological levels of important NAEs in mammalian blood plasma are in the range 2.8–5.2 pmol/ml for anandamide (AEA); 9.4–16.7 pmol/ml for PEA; 8.1–10.3 pmol/ml for oleylethanolamide (OEA) [2], [3] and [4]. However, the NAEs levels in blood plasma could be modified in pathological conditions, e.g., the physiological concentrations of AEA in human plasma are 4 pmol/ml, but these concentrations are increased up to 18–30 pmol/ml in sera of patients with endotoxic shocks [5]. In vivo studies demonstrated that NAEs could accumulate in injured tissues, such as, e.g., in myocardium infarcted areas [6], and in post decapitative brain ischemia [7].

AND:

Palmitoylethanolamide (C16:0) (PEA), a shorter and fully saturated analogue of anandamide, exhibits a number of biochemical, physiological and pharmacological effects [12] and [13]. However, its mechanism of action remains unclear [12] and [13] and its effects are not always reproducible. Among the others, it was identified as the anti-inflammatory principle present in many natural products, and its anti-inflammatory properties were confirmed by recent research [12], [13] and [14], although they seem less marked in human systems [13]. In vitro studies demonstrated that PEA inhibits the nitric oxide production in macrophages [15], affects the time course of capacitation of human spermatozoa [16], and increases the PLA2 hydrolytic activity [17]. In those studies, PEA concentrations inducing significant effects ranged from 5 [16] to 30 μM [17]. Physiologically relevant concentrations of PEA (3 nM–3 μM) [18] may also have important physiological and/or pharmacological effects. For example, 300 nM PEA was shown to protect rat isolated heart against ischemia [19].

Forms the introduction of a hallmark paper on the protective aspects of the natural painkiller palmitoylethanolamide, written by Zolese et al. Based on their knowledge of blood fats (cholesterol etc) and the detrimental effects of oxydation, the authors conducted a study in order to evaluate the possible effect of physiologically relevant concentrations of PEA on the resistance of plasma lipoproteins to oxidation.

They found in their in vitro experiments indicatations of anti-oxidative effects of PEA on the oxidation of LDL, isolated from plasma after incubation with this endogenous fatty acid amide.The protective effect of PEA occurs in physiological and supraphysiological conditions, such also takes place during for instance septic shock:

It has to be stressed that the anti-oxidant effect is obtained at low PEA concentrations in plasma is similar to those observed in pathological conditions, such as endotoxic shock

Main source:

Zolese G, Bacchetti T, Ambrosini A, Wozniak M, Bertoli E, Ferretti G. Increased plasma concentrations of palmitoylethanolamide, an endogenous fatty acid amide, affect oxidative damage of human low-density lipoproteins: an in vitro study. Atherosclerosis. 2005 Sep;182(1):47-55.

Other references

[1]
HS Hansen, B. Moesgaard, H.H. Hansen, G. Petersen
N-Acylethanolamines and precursor phospholipids—relation to cell injury
Chem Phys Lipids, 108 (2000), pp. 135–150

[2]
A. Giuffrida, D. Piomelli
Isotope dilution GC/MS determination of anandamide and other fatty acylethanolamides in rat blood plasma
FEBS Lett, 422 (1998), pp. 373–376

[3]
A. Giuffrida, F. Rodriguez de Fonseca, D. Piomelli
Quantification of bioactive acylethanolamides in rat plasma by electrospray mass spectrometry
Anal Biochem, 280 (2000), pp. 87–93

[4]
A. Giuffrida, F. Rodriguez de Fonseca, F. Nava, P. Loubet-Lescoulie, D. Piomelli
Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404
Eur J Pharmacol, 408 (2000), pp. 161–168

[5]
Y. Wang, Y. Liu, Y. Ito et al.
Simultaneous measurement of anandamide and 2-arachidonoylglycerol by polymyxin B-selective adsorption and subsequent high-performance liquid chromatography analysis: increase in endogenous cannabinoids in the sera of patients with endotoxic shock
Anal Biochem, 294 (2001), pp. 73–82

[6]
H.H.O. Schmid, P.C. Schmid, V. Natarajan
N-Acylated glycerophospholipids and their derivatives
Prog Lipid Res, 29 (1990), pp. 1–43

[7]
H.H.O. Schmid, P.C. Schmid, E.V. Berdyshev
Cell signaling by endocannabinoids and their congeners: questions of selectivity and other challenges
Chem Phys Lipids, 121 (2002), pp. 111–134

[SD-008]
[8]
L. De Petrocellis, D. Melck, T. Bisogno, V. Di Marzo
Endocannabinoids and fatty acid amides in cancer, inflammation and related disorders
Chem Phys Lipids, 108 (2000), pp. 191–209

[9]
E.V. Berdyshev, P.C. Schmid, R.J. Krebsbach et al.
Cannabinoid-receptor-independent cell signalling by N-acylethanolamines
Biochem J, 360 (2001), pp. 67–75

[10]
R. Mechoulam, E. Fride, V. Di Marzo
Endocannabinoids
Eur J Pharmacol, 359 (1998), pp. 1–18

[11]
K.O. Jonsson, S. Vandevoorde, D.M. Lambert, G. Tiger, C.J. Fowler
Effects of homologues and analogues of palmitoylethanolamide upon the inactivation of the endocannabinoid anandamide
Br J Pharmacol, 133 (2001), pp. 1263–1275

[SD-008]
[12]
C.J. Fowler
Plant-derived, synthetic and endogenous cannabinoids as neuroprotective agents. Non-psychoactive cannabinoids, ‘entourage’ compounds and inhibitors of N-acyl ethanolamine breakdown as therapeutic strategies to avoid pyschotropic effects
Brain Res Brain Res Rev, 41 (2003), pp. 26–43

[13]
D.M. Lambert, S. Vandevoorde, K.O. Jonssonand, C.J. Fowler
The palmitoylethanolamide family: a new class of anti-inflammatory agents?
Curr Med Chem, 9 (2002), pp. 663–674

[SD-008]
[14]
H.H. Schmid, E.V. Berdyshev
Cannabinoid-receptor-inactive N-acylethanolamines and other fatty acid amides: metabolism and function
Prostaglandins Leukot Essent Fatty Acids, 66 (2002), pp. 363–376

[15]
R.A. Ross, H.C. Brockie, R.G. Pertwee
Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide
Eur J Pharmacol, 401 (2000), pp. 121–130

[16]
A. Ambrosini, G. Zolese, M. Wozniak et al.
Idiopathic infertility: susceptibility of spermatozoa to in-vitro capacitation, in the presence and the absence of palmitylethanolamide (a homologue of anandamide), is strongly correlated with membrane polarity studied by Laurdan fluorescence
Mol Hum Reprod, 9 (2003), pp. 381–388

[17]
G. Zolese, M. Wozniak, P. Mariani, L. Saturni, E. Bertoli, A. Ambrosini
Different modulation of phospholipase A2 activity by saturated and monounsaturated N-acylethanolamines
J Lipid Res, 44 (2003), pp. 742–753
E.V. Berdyshev, E. Boichot, N. Germain, N. Allain, J.P. Anger, V. Lagente
Influence of fatty acid ethanolamides and delta9-tetrahydrocannabinol on cytokine and arachidonate release by mononuclear cells
Eur J Pharmacol, 330 (1997), pp. 231–240

[19]
P. Lepicier, J.F. Bouchard, C. Lagneux, D. Lamontagne
Endocannabinoids protect the rat isolated heart against ischaemia
Br J Pharmacol, 139 (2003), pp. 805–815

[20]
N.M. Gulaya, A.I. Kuzmenko, V.M. Margitich et al.
Long-chain N-acylethanolamines inhibit lipid peroxidation in rat liver mitochondria under acute hypoxic hypoxia
Chem Phys Lipids, 97 (1998), pp. 49–54

[21]
N.L. Parinandi, H.H. Schmid
Effects of long-chain N-acylethanolamines on lipid peroxidation in cardiac mitochondria
FEBS Lett, 237 (1988), pp. 49–52

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: