EFAD Animals Are Hard To Kill With Mechanical Trauma?

[paymanz]

in one of ray's speaks he mentioned it ,do you guys have any detailed info about this? any reference?

its very interesting.

 

[paymanz]

About one year ago i asked him this question and here is his respond:

"My computer is freezing up, if i can find the whacked-rat publication I’ll send it later.

Prostaglandins Leukot Med. 1986 Aug;23(2-3):123-7.
Essential fatty acid deficiency: a new look at an old problem.
Lefkowith JB, Evers AS, Elliott WJ, Needleman P.
Essential fatty acid (EFA) deficiency is a useful tool to study the role of arachidonate and its metabolites in various physiologic and pathologic states.
Recent studies have clarified the effects of EFA deficiency on membrane arachidonate and its metabolites, and have demonstrated that 20:3(n-9) (which accumulates in EFA deficiency) can be metabolized to a variety of eicosanoids. EFA deficiency has been shown to exert an anti-inflammatory effect. The mechanism of this effect may in part be mediated through a decrease in leukocyte leukotriene formation. In contrast, studies using the novel fatty acid, columbinic acid, have shown that the epidermal dysfunction seen in EFA deficiency may be a function of linoleate and its lipoxygenase metabolites rather than of arachidonate and the prostaglandins. Finally, it has recently been shown that EFAdeficiency potentiates the effects of volatile anesthetics. EFA deficiency may thus provide a useful tool to investigate the molecular mechanism of these drugs.

Circ Shock. 1990 Jun;31(2):159-70.
Resistance of essential fatty acid-deficient rats to endotoxin-induced increases
in vascular permeability.
Li EJ, Cook JA, Spicer KM, Wise WC, Rokach J, Halushka PV.
Department of Physiology, Medical University of South Carolina, Charleston
29425.
Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is
associated with reduced synthesis of certain arachidonic acid metabolites. It
was hypothesized that EFAD rats would manifest decreased vascular permeability
changes during endotoxemia as a consequence of reduced arachidonic acid
metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric
localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red
blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera
imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats
exhibited less hemoconcentration as determined by % HCT than normal rats (47 +/-
2% vs. 54 +/- 1% respectively, P less than 0.01). Endotoxin caused a less severe
change in permeability index in the splanchnic region in EFAD rats than in
normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1
respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric
localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats.
Supplementation with ethyl-arachidonic acid did not enhance susceptibility of
EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA.
Leukotrienes have been implicated as mediators of increased vascular
permeability in endotoxin shock. Since LTC3 formation has been reported to be
increased in EFA deficiency, we hypothesized that LTC3 may be less potent than
LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was
compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial
pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm
Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs.
75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4
receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.
Infusion of LTC4 (4 micrograms/kg/min) in normal rats induced a rise in HCT from
44 +/- 1% to 51 +/- 1% (P less than 0.01), which was greater (P less than 0.05)
than the rise induced by LTC3 (47 +/- 1% to 49 +/- 1%). The results showing that
EFAD rats are resistant to endotoxin-induced increases in HCT and vascular
permeability raise the possibility that this may, in part, be a result of
preferential LTC3 production that is less potent than LTC4.

Agents Actions Suppl. 1977;2:47-59.
Comparison of the mediator release from platelets and the development of acute
inflammation in rats which lack prostaglandin precursors.
Bult H, Bonta IL.
Rat platelet rich plasma (PRP) generates prostaglandin endoperoxide-like
activity, thromboxane A2 (TXA2) and stable prostaglandins (PGs) after collagen
addition. Of the stable PGs, PGE is the main product and its formation is
related to the dose of collagen. Indomethacin and eicosatetraynoic acid (TYA),
both cyclo-oxygenase inhibitors, inhibit TXA2 and PGE formation simultaneously.
PRP of essential fatty acid deficient (EFAD) rats, however, generates far less
PG-endoperoxide like activity, TXA2 and PGE, though the release of serotonin
(5-HT) is unaltered. In normal rats a marked inhibition of the cyclo-oxygenase
by TYA also has no effect on 5-HT release. For these 2 reasons the role of PG
endoperoxides and TXA2 seems to be unimportant for the 5-HT release reaction.
The diminished biosynthesis of PGs and TXA2 in EFAD PRP is not due to an
impaired cyclo-oxygenase activity since addition of AA causes an equal formation
of PGE in both types of PRP. The use of platelets as in-vitro model for testing
anti-inflammatory activity of drugs is discussed. The results, obtained with
platelets support the hypothesis that the main reason for the decreased acute
inflammatory reaction in EFAD rats is a diminished supply of endogenous PG
precursors.

J Pharm Pharmacol. 1977 Jan;29(1):1-7.
Acute anti-inflammatory effects of aspirin and dexamethasone in rats deprived of
endogenous prostaglandin precursors.
Bonta IL, Bult H, Vincent JE, Zijlstra FJ.
Paw oedema, induced by carrageenan, was potentiated in normal rats by
arachidonic acid and bishomo-gamma-linoleic acid, but not by
5,8,11-eicosatrienoic acid. The latter is not an endogenous prostaglandin
precursor, but replaces the other two in essential fatty acid deficient (EFAD)
rats. Carrageenan oedema was partially suppressed in these EFAD rats. Aspirin
exhibited equal suppression of carrageenan oedema in both normal and EFAD rats,
despite the fact that, in the latter, prostaglandins are of negligible
importance. The anti-inflammatory effect of dexamethasone was also identical in
both normal and EFAD rats. The view that interference with the
prostaglandin-system explains the acute anti-inflammatory effects of the two
drugs, is discussed, in relation to the present results.

J Exp Med. 1993 Dec 1;178(6):2261-5.
Effect of dietary supplementation with n-9 eicosatrienoic acid on leukotriene B4
synthesis in rats: a novel approach to inhibition of eicosanoid synthesis.
James MJ, Gibson RA, Neumann MA, Cleland LG.
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia.
Studies were undertaken to assess the biochemical effects of dietary
supplementation with n-9 eicosatrienoic acid (ETrA), an arachidonic acid
analogue that is normally present in cell membranes at very low levels but is
raised in the presence of essential fatty acid deficiency (EFAD). The
incorporation of dietary ETrA into rat neutrophils and its effect on
A23187-stimulated 5-lipoxygenase metabolism in these cells was examined; in
addition, the effect of ETrA was compared with that of another arachidonic acid
analogue, eicosapentaenoic acid (EPA), which is known to accumulate in cell
membranes and inhibit synthesis of leukotriene B4 (LTB4) a product of the
5-lipoxygenase metabolic pathway. Rats were fed a defined diet that was
sufficient in essential fatty acids and that contained EPA or ETrA (0.014% of
energy) or no added fatty acid, for 3 wk. In the cells from ETrA-fed rats, LTB4
synthesis was inhibited relative to control values, but synthesis of the other
products of 5-lipoxygenase metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE)
and the all-trans isomers of LTB4, were not inhibited. This pattern indicates
inhibition of LTA hydrolase in ETrA-fed rats. In EPA-fed rats, there was
inhibition of LTB4 and the all-trans isomers of LTB4, but there was no
inhibition of 5-HETE. This pattern indicates inhibition of LTA synthase in
EPA-fed rats. The results establish that dietary ETrA effectively
inhibits
synthesis of the inflammatory mediator, LTB4, and suggest that ETrA may confer
antiinflammatory benefits similar to those observed with EFAD or dietary fish
oil (which contains EPA). Because ETrA is substantially less unsaturated than
EPA, it can be expected to have greater chemical stability, which could be an
important practical advantage when used as a dietary constituent or supplement.