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Effects of n−3 and n−6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZB×NZW F1 mice

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Lipids

Abstract

Menhaden fish oil (FO) containing n−3 fatty acids dramatically extends the life span and delays the onset and progression of autoimmune disease in (NZB×NZW)F1 (B/W) female mice as compared to those fed corn oil (CO) rich in n−6 lipids. As an inefficient antioxidant defense system has been linked to autoimmune diseases, the present study was undertaken to determine whether the protective action of n−3 lipids is mediated through their antioxidant defense system. Weanling B/W mice were fed a nutritionally adequate, semipurified diet containing CO or krill oil (KO) or FO at 10% level (w/w)ad libitum until the mice were 6.5 months old. All diets contained the same level of vitamin E (21.5 mg/100 g diet). We compared the effects of feeding n−6 and n−3 lipids on survival, kidney disease, hepatic microsomal lipid composition, peroxidation, and on the activity and mRNA expression of the antioxidant enzymes catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in 6.5-month-old B/W mice. The results showed that when compared to livers from CO-fed mice, livers from KO- and FO-fed mice showed: (i) significantly higher (P<0.001) activities and expression of CAT, GSH-Px and SOD; (ii) significantly lower (P<0.001) arachidonic acid (20∶4n−6) and linoleic acid (18∶2n−6) and higher (P<0.001) eicosapentaenoic acid (20∶5n−3) and docosahexaenoic acid (22∶6n−3) levels in hepatic microsomes; and (iii) significantly lower (P<0.001) estimated peroxidation indices and thiobarbituric acid reactive substances generation. The data indicate that one of the mechanisms through which the n−3 lipids delay the onset of autoimmune diseases in B/W mice may be through maintenance of higher activities and expression of hepatic antioxidant enzymes.

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Abbreviations

B/W mice:

(NZB×NZW) F1 mice

CAT:

catalase

CO:

corn oil

EDTA:

ethylenediaminetetraacetic acid

FO:

fish oil

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

GSH:

glutathione reduced form

GSH-Px:

glutathione peroxidase

KO:

krill oil

NADPH:

β-nicotinamide adenine dinucleotide phosphate, reduced form

SDS:

sodium dodecylsulfate

SLE:

systemic lupus erythematosus

SOD:

superoxide dismutase

SSC:

sodium chloride/sodium citrate buffer

TBARS:

thiobarbituric acid reactive substances

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Venkatraman, J.T., Chandrasekar, B., Kim, J.D. et al. Effects of n−3 and n−6 fatty acids on the activities and expression of hepatic antioxidant enzymes in autoimmune-prone NZB×NZW F1 mice. Lipids 29, 561–568 (1994). https://doi.org/10.1007/BF02536628

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