COMMENT:

In your mind.  LOL.

If you'd actually take a look at the literature, you'd see that we've
progressed a long way from the simplistic PUFA = radical = disease
model. In fact, omega-3 EFAs decrease inflammation, and whereever you
decrease inflammation, you decrease free radical activity. Does giving
fish oil increase free radical activity. No, in most cases and in most
models, quite the other way.

1: Ann Clin Lab Sci. 2005 Spring;35(2):169-73.

Brief communication: omega-3 essential fatty acid supplementation and
erythrocyte oxidant/antioxidant status in rats.

Iraz M, Erdogan H, Ozyurt B, Ozugurlu F, Ozgocmen S, Fadillioglu E.

Department of Pharmacology, Inonu University Faculty of Medicine,
Malatya.
mustafairaz@yahoo.com

Fish oil contains large amounts of essential omega-3 fatty acids, such
as
eicosapentaenoic and docosahexaneoic acids, which are building
structures of
cell membranes. The goal of this study was to elucidate the effects of
dietary
omega-3 fatty acid supplementation on the oxidant/antioxidant status of
erythrocytes in rats. The malondialdehyde (MDA) and nitric oxide (NO)
levels and
the catalase (CAT), superoxide dismutase (SOD), and glutathione
peroxidase
(GSH-PX) activities were assayed in erythrocytes of male Wistar albino
rats
after 30 days of dietary supplementation with fish oil (0.4 g/kg/day).
Erythrocyte CAT activity in the treated group was increased in
comparison with
the control group. Erythrocyte MDA and NO levels were lower in the
treated group
than the controls. Erythrocyte GSH-Px and SOD activities did not differ
significantly in the 2 groups. Negative correlations were found between
SOD and
CAT activities, and between SOD and GSH-Px activities in the treated
group. In
conclusion, omega-3 fatty acid supplementation helps to prevent lipid
peroxidation and to safeguard erythrocytes from oxidative injury.
Dietary
supplementation with omega-3 fatty acids might possibly protect tissues
from
oxygen free radical injury in the various diseases in which the
oxidant/antioxidant defense mechanisms are disturbed.

PMID: 15943181 [PubMed - indexed for MEDLINE]

2: Prostaglandins Leukot Essent Fatty Acids. 2005 Apr;72(4):257-65.

Fish oil before cardiac surgery: neutrophil activation is unaffected
but
myocardial damage is moderated.

Charman A, Muriithi EW, Milne E, Wheatley DJ, Armstrong RA, Belcher PR.

Centre for Nutrition & Food Research, Queen Margaret University
College,
Edinburgh EH12 8TS, UK.

Could pre-operative dietary intervention with fish oil reduce
neutrophil
activation and myocardial damage associated with cardiopulmonary bypass
(CPB)?
Patients were randomised to receive either 8 g/day fish oil (n=22) or
placebo
(n=18) for 6 weeks. Neutrophil activation, apoptosis and cardiac damage
were
measured. Demographics and operative variables were similar. Fish oil
diet
decreased plasma VLDL from 0.69+/-0.34 to 0.51+/-0.24 mmol/l and
triglycerides
from 1.68+/-0.70 to 1.39+/-0.54 mmol/l. HDL cholesterol increased from
0.94+/-0.27 to 1.03+/-0.26 mmol/l demonstrating significant treatment
effects
(P=0.007, 0.02 and 0.0003, respectively) as well as compliance with
treatment.
There were no significant differences in ex vivo
N-formyl-methionyl-leucyl-phenylalanine-stimulated neutrophil
superoxide anion
generation or myeloperoxidase release at recruitment, pre-operatively
and at
end-CPB. Apoptosis at end-CPB was equally reduced in both groups from
23+/-9% to
13+/-4% in the fish oil group (P<0.001) and 35+/-14% to 15+/-3% in the
placebo
group (P=0.001). At end-CPB overall troponin I levels averaged
0.91+/-0.60 ng/ml
which clearly exceeded diagnostic levels (0.15 ng/ml). At 24h troponin
I fell
significantly in the fish oil group to 46+/-23% of end-CPB levels
(P=0.0002)
whereas it peaked in the placebo group to 107+/-72% (P=0.098 vs.
end-CPB); this
difference was significant: P=0.013. At 48 h the placebo-treated
patients had
higher troponins but not significantly so (P=0.059).
Area-under-the-curve
analysis did not conclusively support this (P=0.068). We conclude that
fish oil
did not significantly decrease post-CPB neutrophil activation (as
detected ex
vivo) but may moderate post-operative myocardial damage.

Publication Types:
   Clinical Trial
   Randomized Controlled Trial

PMID: 15763437 [PubMed - indexed for MEDLINE]

3: Pharmacol Biochem Behav. 2004 Dec;79(4):651-9.

Protective effect of chronic ethyl docosahexaenoate administration on
brain
injury in ischemic gerbils.

Cao DH, Xu JF, Xue RH, Zheng WF, Liu ZL.

Department of Biology, Nanjing University, 22 Hankou Road, Jiangsu
210093, PR
China.

There is evidence that the excessive generation of reactive oxygen free
radicals
contributes to the brain injury associated with cerebral ischemia. In
the
present study, the protective effect of chronic administration of ethyl
docosahexaenoate (E-DHA) against oxidative brain injury was evaluated
in the
gerbil model of transient cerebral ischemia. Weanling male gerbils were
orally
pretreated with either E-DHA (200 mg/kg) or vehicle, once a day, for 10
weeks
and subjected to bilateral occlusion of common carotid arteries for 10
min. At
the different reperfusion times, E-DHA pretreatment significantly
inhibited the
increases in the production of brain salicylate-derived
2,5-dihydroxybenzoic
acid (2,5-DHBA) and content of brain malonildialdehyde (MDA). The
superoxide
dismutase (SOD) activity was not modified; however, pretreatment with
E-DHA
significantly prevented the level of brain-reduced glutathione (GSH)
and
activities of brain glutathione peroxidase (GSH-P(X)) and catalase
(CAT) from
declines caused by cerebral ischemia. Moreover, ischemia and
reperfusion-induced
delayed neuronal loss in the hippocampus CA1 sector and locomotor
hyperactivity
were also significantly attenuated by pretreatment with E-DHA. These
results
suggested that the neuroprotective effect of E-DHA might be due to its
antioxidant property.

PMID: 15582673 [PubMed - indexed for MEDLINE]

4: Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jul;28(4):693-8.

Hypothalamic superoxide dismutase, xanthine oxidase, nitric oxide, and
malondialdehyde in rats fed with fish omega-3 fatty acids.

Songur A, Sarsilmaz M, Sogut S, Ozyurt B, Ozyurt H, Zararsiz I,
Turkoglu AO.

Department of Anatomy, Afyon Kocatepe University Medical School,
Turkey.

Phospholipids located in the cellular membrane play a critical role in
the
fluid-mosaic model of membrane structure and membrane function.
Evidence is
mounting for the role of abnormal phospholipid metabolism in some
neuropsychiatric disorders including schizophrenia. As an important
essential
fatty acid (EFA), omega-3 (omega-3) fatty acid series are found in
large amounts
in fish oil. The aim of this experimental study was to assess the
changes of
some of the oxidant and antioxidant parameters in the hypothalamus of
rats fed
with omega-3 EFA diet (0.4 g/kg/day) for 30 days. Eight control rats
and nine
rats fed with omega-3 were decapitated under ether anesthesia, and
hypothalamus
was removed immediately. Malondialdehyde (MDA) and nitric oxide (NO)
levels as
well as superoxide dismutase (SOD) and xanthine oxidase (XO) enzyme
activities
in the hypothalamus were measured. SOD activity was significantly
decreased in
omega-3 EFA treated group compared to control group (p < 0.014). Tissue
MDA and
NO levels were also decreased in omega-3 EFA treated group compared to
control
rats (p < 0.0001). Xanthine oxidase activity was found to be increased
in
omega-3 EFA treated rats when compared to the control group (p <
0.0001). Taken
together, this preliminary animal study provides strong support for a
therapeutic effect of omega-3 EFA in some neuropsychiatric disorders in
which
reactive oxygen species (ROS) are recently accused to be an important
physiopathogenetic factor.

PMID: 15276695 [PubMed - indexed for MEDLINE]

5: Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):149-52.

Effect of fish oil supplementation on plasma oxidant/antioxidant status
in rats.

Erdogan H, Fadillioglu E, Ozgocmen S, Sogut S, Ozyurt B, Akyol O,
Ardicoglu O.

Department of Physiology, Faculty of Medicine, Gaziosmanpasa
University, Tokat
60100, Turkey. herdogan@gop.edu.tr

The aim of this study was to investigate effect of dietary omega-3
fatty acid
supplementation on the indices of in vivo lipid peroxidation and
oxidant/antioxidant status of plasma in rats. The plasma thiobarbituric
acid
reactive substances (TBARS) and nitric oxide (NO) levels, and
activities of
xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione
peroxidase
(GSH-PX) were studied in male Wistar Albino rats after ingestion of 0.4
g/kg
fish oil (rich in omega-3 fatty acids, eicosapentaenoic acid and
docosahexaenoic
acid) for 30 days and compared to untreated control rats. The rats in
the
treated group had significantly higher SOD activity (P < 0.001), NO
levels (P <
0.01) and decreased TBARS levels (P < 0.05) with respect to controls
whereas
GSH-Px and XO activities were not significantly different between the
groups.
None of the measured parameters had significant correlation with each
other in
both groups. We conclude that dietary supplementation of omega-3 fatty
acids may
enhance resistance to free radical attack and reduce lipid
peroxidation. These
results support the notion that omega-3 fatty acids may be effective
dietary
supplements in the management of various diseases in which
oxidant/antioxidant
defence mechanisms are decelerated.

PMID: 15253883 [PubMed - indexed for MEDLINE]

6: Metabolism. 2004 Jan;53(1):59-65.

Effects of different dietary oils on inflammatory mediator generation
and fatty
acid composition in rat neutrophils.

de La Puerta Vazquez R, Martinez-Dominguez E, Sanchez Perona J,
Ruiz-Gutierrez
V.

Departamento de Farmacologia, Facultad de Farmacia, Universidad de
Sevilla,
Seville, Spain.

Virgin olive oil (VOO) compared with fish oil (FO) and evening primrose
oil (PO)
on the ability of stimulated leukocytes to produce inflammatory
mediators was
investigated in rats. Weaned Wistar rats were fed a basal diet (BD) (2%
by
weight of corn oil) or diets containing 15% by weight of VOO, PO, or
FO. After 8
weeks, glycogen-elicited peritoneal polymorphonuclear leukocytes,
mainly
neutrophils, were isolated. The calcium-ionophore stimulated
neutrophils (2.5 x
10(6) cells/mL) obtained from rats fed the different oils produced a
higher
release of lysosomal enzymes (beta-glucuronidase, lysozyme, and
myeloperoxidase
[MPO]) compared with those fed BD. The production of reactive oxygen
species
(ROS) in response to the stimulant,
12-O-tetradecanoyl-phorbol-13-acetate (TPA),
by neutrophils from the VOO group (15.44 nmol of O(2)(-) and 6.56 nmol
of
H(2)O(2)) was similar to the BD group (12.01 nmol O(2)(-) and 8.49 nmol
H(2)O(2)) and significantly lower than the PO (20.90 nmol O(2)(-) and
10.84 nmol
H(2)O(2)) and FO (20.93 nmol O(2)(-) and 12.79 nmol H(2)O(2)) groups.
The
cyclooxygenase-derived eicosanoid production was reduced by the lipid
enrichment
of the diets. Whereas the generation of prostaglandin E(2) (PGE(2)) was
significantly decreased in VOO (5.40 ng/mL), PO (4.95 ng/mL), and FO
(1.44
ng/mL) groups compared with BD (8.19 ng/mL), thromboxane B(2) (TXB(2))
reduction
was especially significant in neutrophils from the FO diet group (14.67
ng/mL
compared with 26.69 ng/mL from BD). These experimental data suggest
that FO and
PO, as well as VOO, could be considered a valuable strategy in
preventing the
generation of some inflammatory mediators.

PMID: 14681843 [PubMed - indexed for MEDLINE]

7: J Am Coll Nutr. 2003 Oct;22(5):388-99.

Effect of dietary n-3 and n-6 oils with and without food restriction on
activity
of antioxidant enzymes and lipid peroxidation in livers of
cyclophosphamide
treated autoimmune-prone NZB/W female mice.

Bhattacharya A, Lawrence RA, Krishnan A, Zaman K, Sun D, Fernandes G.

Department of Medicine, University of Texas Health Science Center, San
Antonio,
Texas 78229-3900, USA.

OBJECTIVE: Cyclophosphamide (CTX), an alkylating agent, is extensively
used in
the treatment of lupus nephritis, but its administration has been
associated
with free radical mediated oxidative stress. The present study was
designed to
investigate the effect of dietary corn oil (CO), fish oil (FO) and food
restriction (FR) on the activities of hepatic antioxidant enzymes,
fatty acid
composition and lipid peroxidation following CTX administration in
autoimmune-prone NZB/W female mice. METHODS: Autoimmune-prone NZB/W
female mice
were fed either ad libitum (AL) or food restricted (60% of AL intake),
semipurified diets containing 5% CO or 5% FO supplemented with equal
levels of
antioxidants and injected with either phosphate buffered saline (PBS),
or CTX
(50 mg/kg body weight) every 10 days. Proteinuria was measured
biweekly. The
treatment was stopped at 10 months and diets were continued until the
mice were
killed at 12 months. Fatty acid composition, activity of antioxidant
enzymes and
lipid peroxidation were analyzed in liver homogenates, and anti-DNA
antibodies
were analyzed in the serum. RESULTS: Mice in the FO/AL dietary group
exhibited
significantly higher liver catalase (CAT), superoxide dismutase (SOD)
and
glutathione peroxidase (GSH-Px) activities compared to the CO/AL
dietary group.
CTX significantly decreased SOD and GSH-Px activity in the FO/AL group
and CAT
and GSH-Px in the CO/AL group. In AL fed mice given CTX, activities of
CAT,
GSH-Px and GST were significantly higher in mice fed FO diets than in
mice fed
CO diets. FR increased the activity of enzymes in both the CO and FO
diet
groups. In FR mice, CTX decreased CAT and GSH-Px activity in both the
CO and FO
dietary groups, but glutathione S-transferase (GST) only in the CO
group. The
decrease in SOD activity was not significant in either of the
restricted groups.
CTX significantly increased generation of thiobarbituric acid reactive
substances (TBARS) in both AL groups. FR significantly decreased lipid
peroxidation in both the CO and FO groups, with or without CTX. CTX
decreased
serum anti-DNA antibody levels in both the CO and FO dietary groups. FR
also
decreased antibody titer in both the CO and FO dietary groups, and it
was
decreased further with CTX treatment. FO fed animals had higher levels
of n-3
fatty acids, whereas CO fed animals had high levels of n-6 fatty acids.
CTX
significantly increased 20:4 and decreased 18:1 in CO/AL fed animals,
whereas it
increased 18:1 and decreased 22:6 in FO/AL fed animals. CONCLUSIONS:
Results
obtained in the present study suggests that FO and, more significantly,
FO
combined with FR can have a beneficial effect in hepatic tissues
subjected to
CTX induced oxidative stress by regulating the activity of antioxidant
enzymes.
In addition, the study also indicates that n-3 and n-6 dietary lipids
are
susceptible to lipid peroxidation, particularly in the presence of a
prooxidant
like CTX, and that FR is beneficial in decreasing lipid peroxidation.
The study
also suggests that FO and CTX can have additive effects in preventing
kidney
disease in NZB/W mice.

PMID: 14559931 [PubMed - indexed for MEDLINE]

8: Nutrition. 2003 Oct;19(10):837-42.

Decreased oxidative stress in patients with ulcerative colitis
supplemented with
fish oil omega-3 fatty acids.

Barbosa DS, Cecchini R, El Kadri MZ, Rodriguez MA, Burini RC, Dichi I.

Laboratory of Biochemistry, Londrina State University, Londrina,
Parana, Brazil.

OBJECTIVE: The potential pathogenicity of free radicals may have a
pivotal role
in ulcerative colitis. Fish oil omega-3 fatty acids exert
anti-inflammatory
effects on patients with ulcerative colitis (UC), but the precise
mechanism of
the action of fish oil on oxidative stress is still controversial. The
aim of
the present work was to verify the blood oxidative stress in patients
with UC
and determine whether the association of sulfasalazine to fish oil
omega-3 fatty
acids is more effective than isolated use of sulfasalazine to reduce
the
oxidative stress. METHODS: Nine patients (seven female and two male;
mean age =
40 +/- 11 y) with mild or moderate active UC were studied in a
randomized
crossover design. In addition to their usual medication (2 g/d of
sulfasalazine), they received fish oil omega-3 fatty acids (4.5 g/d) or
placebo
for 2-mo treatment periods that were separated by 2 mo, when they only
received
sulfasalazine. Nine healthy individuals served as control subjects to
study the
oxidative stress status. Disease activity was assessed by laboratory
indicators
(C-reactive protein, alpha1-acid glycoprotein, alpha1-antitrypsin,
erythrocyte
sedimentation rate, albumin, hemoglobin, and platelet count),
sigmoidoscopy, and
histology scores. Analysis of oxidative stress was assessed by plasma
chemiluminescence and erythrocyte lipid peroxidation, both induced by
tert butyl
hydroperoxide (t-BuOOH) and by plasma malondialdehyde. Antioxidant
status was
assayed by total plasma antioxidant capacity (TRAP) and microsomal
lipid
peroxidation inhibition (LPI). Superoxide dismutase (SOD) and catalase
erythrocyte enzymatic activities were also determined. RESULTS: No
significant
changes were observed in any laboratory indicator or in the
sigmoidoscopy or
histology scores, with the exception of erythrocyte sedimentation rate,
which
decreased with both treatments. Oxidative stress was demonstrated by
significant
decreases in TRAP and LPI levels, increased chemiluminescence induced
by
t-BuOOH, and higher SOD activity in patients with UC. Treatment with
fish oil
omega-3 fatty acids reverted the chemiluminescence induced by t-BuOOH
and LPI to
baseline levels but that did not occur when patients received only
sulfasalazine. Levels of plasma malondialdehyde, erythrocyte lipid
peroxidation,
and catalase were not different from those in the control group.
CONCLUSIONS:
The results indicated that plasma oxidative stress occurs in patients
with UC,
and there was a significant decrease when the patients used
sulfasalazine plus
fish oil omega-3 fatty acids. However, there was no improvement in most
laboratory indicators, sigmoidoscopy, and histology scores. The results
suggested that omega-3 fatty acids may act as free radical scavengers
protecting
the patients against the overall effect of oxidative stress.

Publication Types:
   Clinical Trial
   Randomized Controlled Trial

PMID: 14559317 [PubMed - indexed for MEDLINE]