Dietary DHA/EPA supplementation ameliorates diabetic nephropathy by protecting from distal tubular cell damage

Uljević, Marija Vitlov; Starčević, Kristina; Mašek, Tomislav; Bočina, Ivana; Restović, Ivana; Kević, Nives; Racetin, Anita; Kretzschmar, Genia; Grobe, Maximilian; Vukojević, Katarina; Saraga-Babić, Mirna; Filipović, Natalija

doi:10.1007/s00441-019-03058-y

Cited by 30 publications

(26 citation statements)

References 58 publications

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“…The duration of the intervention lasted for 44 days: 14 days before induction of the DM1 and then 30 days after DM1 induction. In our previous works we proved that the same intervention resulted in substantial changes in total fatty acid composition of different tissues, as well as profound changes in fatty acid composition of phospholipids [27,28].…”

Section: Experimental Designmentioning

confidence: 74%

“…Hearts were extracted and stored in buffered 4% paraformaldehyde for histological analyses. Tissues were dehydrated by ethanol and embedded in paraffin wax as described previously [ 28 ]. Paraffin blocks were cut in 5 μm-thick sections and mounted on histological slides.…”

Section: Methodsmentioning

confidence: 99%

“…Diabetes was induced in three groups: stz, stz+n6 and stz+DHA, two weeks after the beginning of special diet protocol, by injecting intraperitoneally with 55 mg/kg body weight of streptozotocin dissolved in citrate buffer (pH 4.5) after overnight fasting. The group c received pure citrate buffer solution intraperitoneally, as described previously [28]. The same diet protocol lasted until the end of the experiment.…”

Section: Experimental Designmentioning

confidence: 99%

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Effects of Different n6/n3 PUFAs Dietary Ratio on Cardiac Diabetic Neuropathy

Urlić

Urlic

et al. 2020

Nutrients

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We studied the influence of experimentally induced DM1, in combination with different dietary n6:n3 polyunsaturated fatty acid (PUFA) ratios on different types of nerve fibers in rat myocardium, in order to reveal whether protective/unfavorable effects of different PUFAs on myocardial function in diabetic patients could be a (partial) repercussion of their effect on the changes in cardiac innervation. The control group (c) and diabetic group (stz) were fed with an n6/n3 ratio of ≈7; the diet of the stz+n6 group had an n6/n3 ratio ≈60, while the diet for the stz+DHA group contained 2.5% of fish oil (containing 16% eicosapentaenoic acid—EPA and 19% docosahexaenoic acid—DHA), n6/n3 ratio of ≈1. DM1 was induced by i.p. injection of streptozotocin (55 mg/kg) and rats were euthanized 30 days after induction. Immunohistochemistry was used for the detection and quantification of different types of neuronal fibers in the cardiac septum. We found changes in cardiac innervations characteristics for the initial phase of experimental DM1, which manifested as an increase in total number and area density of all neuronal fibers, measured by Pgp9.5 immunoreactivity. By detailed analysis, we found that this increase consisted mostly of heavy myelinated NF200 immunoreactive fibers and TH immunoreactive sympathetic fibers, while the density of ChAT immunoreactive parasympathetic fibers decreased. In the deep (middle) part of the myocardium, where rare fibers (of all studied types) were found, significant differences were not found. Surprisingly, we found a more consistent protective effect of n6 PUFAs, in comparison to n3 PUFAs supplementation. These results may provide a better understanding of the potential impacts of different PUFA ratios in the diet of diabetic patients on cardiac innervation and genesis and outcome of diabetic autonomic cardiomyopathy.

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Section: Experimental Designmentioning

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

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Effects of Different n6/n3 PUFAs Dietary Ratio on Cardiac Diabetic Neuropathy

Urlić

Urlic

et al. 2020

Nutrients

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“…Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson's staining were performed as per standard protocols, and the tissue sections were observed under a light microscope (Leica DM60008, Kyoto, Japan). For transmission electron microscopy (TEM), the renal cortices were fixed in 2% glutaraldehyde (Servicebio, Wuhan, China), cut into ultrathin sections, and stained accordingly [ 34 ]. The samples were observed under a TEM (JEM-1400 plus, JEOL, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Ginsenoside Rg1 Alleviates Podocyte Injury Induced by Hyperlipidemia via Targeting the mTOR/NF‐κB/NLRP3 Axis

Wang

Gao

Yue

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Podocyte injury plays an important role in diabetic nephropathy (DN). The aim of this study was to determine the potential therapeutic effects of the ginsenoside Rg1 on hyperlipidemia-stressed podocytes and elucidate the underlying mechanisms. Methods. In vitro and in vivo models of DN were established as previously described, and the expression levels of relevant markers were analyzed by Western blotting, real-time Polymerase Chain Reaction (PCR), immunofluorescence, and immunohistochemistry. Results. Ginsenoside Rg1 alleviated pyroptosis in podocytes cultured under hyperlipidemic conditions, as well as in the renal tissues of diabetic rats, and downregulated the mammalian target of rapamycin (mTOR)/NF-κB pathway. In addition, Rg1 also inhibited hyperlipidemia-induced NLRP3 inflammasome in the podocytes, which was abrogated by the mTOR activator L-leucine (LEU). The antipyroptotic effects of Rg1 manifested as improved renal function in the DN rats. Conclusion. Ginsenoside Rg1 protects podocytes from hyperlipidemia-induced damage by inhibiting pyroptosis through the mTOR/NF-κB/NLRP3 axis, indicating a potential therapeutic function in DN.

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“…In particular, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) are found to be in high concentrations in various species of fish, such as herring [ 10 , 11 , 12 ], tuna [ 13 ], sea bream [ 14 ], beluga [ 15 ], rainbow trout [ 16 ], salmon [ 12 , 17 , 18 ], boarfish [ 12 ], and teleost [ 2 ]. Both EPA and DHA exert beneficial effects on various inflammatory diseases, such as Alzheimer’s disease [ 19 ], cardiovascular diseases [ 20 ], cancer [ 21 , 22 ], diabetes [ 23 , 24 ], thrombosis [ 12 , 17 , 18 ], and inflammatory activity [ 25 , 26 ]. A recent research study has reported that when n-3 PUFA binds with polar lipids, it exerts differential bioavailability and biological effects upon consumption in contrast to neutral forms of n-3 PUFA [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Neutral Lipids, Glycolipids, and Phospholipids, Isolated from Sandfish (Arctoscopus japonicus) Eggs, Exhibit Anti-Inflammatory Activity in LPS-Stimulated RAW264.7 Cells through NF-κB and MAPKs Pathways

et al. 2020

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Total lipids were extracted from sandfish (Arctoscopus japonicus), and then they were separated into the following three lipid fractions: neutral lipids, glycolipids, and phospholipids. In this study, we analyzed the lipid fractions of A. japonicus eggs and we determined their anti-inflammatory activity in RAW264.7 macrophage cells. In these three lipid-fractions, the main fatty acids were as follows: palmitic acid (16:0), oleic acid (18:1n-9), docosahexaenoic acid (DHA, 22:6n-3), and eicosapentaenoic acid (EPA, 20:5n-3). Among the lipid fractions, phospholipids showed the highest concentration of DHA and EPA (21.70 ± 1.92 and 18.96 ± 1.27, respectively). The three lipid fractions of A. japonicus significantly suppressed the production of NO in macrophages. Moreover, they also significantly inhibited the expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α, in a dose-dependent manner. Furthermore, the lipid fractions of A. japonicus suppressed the nuclear translocation of NF-κB p65 subunits in a dose-dependent manner. In addition, they attenuated the activation of MAPKs (p38, ERK1/2, and JNK) phosphorylation in LPS-stimulated RAW264.7 cells. These results indicate that all the lipid fractions of A. japonicus exert anti-inflammatory activity by suppressing the activation of NF-κB and MAPK pathways. Therefore, the lipid fractions of A. japonicus might be potentially used as anti-inflammatory agents.

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Dietary DHA/EPA supplementation ameliorates diabetic nephropathy by protecting from distal tubular cell damage

Cited by 30 publications

References 58 publications

Effects of Different n6/n3 PUFAs Dietary Ratio on Cardiac Diabetic Neuropathy

Effects of Different n6/n3 PUFAs Dietary Ratio on Cardiac Diabetic Neuropathy

Ginsenoside Rg1 Alleviates Podocyte Injury Induced by Hyperlipidemia via Targeting the mTOR/NF‐κB/NLRP3 Axis

Neutral Lipids, Glycolipids, and Phospholipids, Isolated from Sandfish (Arctoscopus japonicus) Eggs, Exhibit Anti-Inflammatory Activity in LPS-Stimulated RAW264.7 Cells through NF-κB and MAPKs Pathways

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