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

This paper demonstrates how CR can protect from the negative effects
of Omega-3: "FR significantly decreased lipid peroxidation"

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