Antioxidants (Basel). , 2021, Apr 27;10(5):681. doi: 10.3390/antiox10050681.

Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model.

Mattioli S Collodel G Signorini C et al.

Abstract

Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups (n = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3.5% fish oil + 200 mg/kg vitamin E. Antioxidants (enzymatic and non-enzymatic), oxidative status (malondialdehyde and isoprostanoids), and n-3 and n-6 PUFAs of tissues were analysed. A chain mechanism of oxidant/antioxidant molecules, which largely depended on the particular PUFA composition, was delineated in the different organs. The liver showed an oxidant/antioxidant profile and lipid pathways widely modulated by PUFA and vitamin E administration; on the other hand, the testis’ oxidative profile rather than its lipid profile seemed to be particularly affected, an outcome opposite to that of the brain (modulation operated by dietary PUFA).

Link to Full Text

Key Points

Due to the susceptibility of PUFA to oxidation, the role of antioxidants has received extensive attention. Accordingly, antioxidant protection is always required when dietary PUFAs are supplied. Some studies in rabbits have shown an improvement in muscle oxidative stability by feeding animals with supra-nutritional levels of various antioxidants. As an antioxidant, vitamin E works in synergy with an endogen antioxidant system to scavenge free radicals. This system includes ascorbic acid and thiol antioxidants (e.g., glutathione). This study evaluated the implication of n-3 PUFA dietary supplementation (precursor and LCPs) on the PUFA profile and oxidative status of specific rabbit organs. The lipid oxidative status, isoprostanoid generation, and enzymatic/non-enzymatic antioxidant content were evaluated in the liver, brain, and testis of rabbit bucks fed flaxseed- or fish-oil-enriched diets.

In this study, there was a cooperative interaction among antioxidants, and this activity varied in each organ. The testis showed the highest MDA concentration followed by the brain and the liver, with a trend affected by the dietary supplementation (PUFA and/or vitamin E). Besides the dietary PUFA content, the MDA level was also related to the antioxidant content of tissues: CNT− group showed higher MDA levels in all organs, such as FO and FLAX groups. AA had an important role in restoring oxidised vitamin E: low AA levels were associated with higher vitamin E levels.

The vitamin E levels recorded in the brain and testis were related to the remarkable increase in ALA (testis) and LCPn-3 (brain), which probably determined an exceptional consumption of vitamin E. As the centre of lipid metabolism, the liver displayed a strong oxidant/antioxidant pathway chain, mainly modulated by the GPX activity and secondarily by vitamin E and CAT. Furthermore, the main lipid pathway seemed to be isoprostanoid generation, mainly constituted by F2-IsoPs. In the brain, LCPn-3 had a greater, although mild, influence; this is expected because this organ is the main n-3 PUFA–sensitive tissue. However, the brain showed low isoprostanoid production. The antioxidant pathway was mainly characterised by the activity of secondary antioxidant molecules—i.e., GR and AA—which functioned to restore key molecules (e.g., vitamin E).

The addition of dietary PUFA affects the oxidative status of several organs. In particular, the level of different isoprostanoids can be considered valid biomarkers, besides the evaluation of MDA, to estimate the specific oxidative status of tissues. We delineated a chain mechanism of antioxidant molecules in the different organs; it largely depends on the PUFA composition and the biological fate of the tissues. It was confirmed that the liver is the primary metabolic site because both antioxidant and lipid pathways are widely modulated by PUFA and vitamin E administration. On the other hand, the brain seemed to be particularly affected by the dietary lipid source, whereas the testis was affected by the oxidant/antioxidant pathway. Nevertheless, further investigations are needed to understand the respective role of various isoprostanoids in the different organs (F2-IsoPs, F3-IsoPs, and F4-NeuroPs), also considering that every organ showed a unique trend, associated with the FA profile and their interaction with the antioxidants contained in each organ.