@article {271,
	title = {Eicosapentaenoicacidpreventssaltsensitivityindiabeticratsdecreasingoxidativestress},
	journal = {Nutrition},
	year = {2020},
	abstract = {Salt sensitivity (SS) is associated with increased cardiovascular risk in\&nbsp;type-2 diabetes mellitus (T2-DM) patients due to an increase in renal oxidation. ω-3\&nbsp;polyunsaturated fatty acids have shown antioxidant effects, but a typical Western diet\&nbsp;has limited content of them. In particular, ω-3 PUFAs are able to activate Nrf-2 (nuclear\&nbsp;factor erythroid 2-related factor) to prevent DM-related complications by mitigating\&nbsp;oxidative stress. Therefore, we hypothesized that eicosapentaenoic acid (EPA, ω-3)\&nbsp;modulates SS in T2-DM rats, by decreasing renal oxidative stress via Nrf-2 activation,\&nbsp;and enhancing the anti-inflammatory response via IL-6 modulation. 3-months-old male rats (n=40) were fed with a normal Na-diet (NNaD) and randomly\&nbsp;selected into 4 groups: i. healthy Wistar rats, non-diabetic rats (Wi), ii. diabetic control\&nbsp;(eSS), iii. arachidonic acid-treated eSS (ω-6) (AA), iv. EPA-treated eSS (ω-3) (EPA).\&nbsp;After one year, rats were placed in metabolic cages for 7 days and fed with a NNaD and\&nbsp;followed by a 7 days period with high Na-diet (HNaD). Systolic blood pressure (SBP),\&nbsp;body weight (BW), serum interleukin-6 (IL-6) and reactive oxygen species (ROS) levels\&nbsp;were determined at the end of each 7-day period. Glycated hemoglobin (HbA1c),\&nbsp;triglycerides (TAG), creatinine and cholesterol (Chol) were determined. ROS levels and\&nbsp;Nrf-2 expression in kidney lysates were also assayed. Histological changes were\&nbsp;evaluated. T-test or ANOVA were used for statistical analysis. Following\&nbsp;HNaD, SBP increased in both control eSS and AA groups, but not in EPA and Wi groups. However, HbA1c remained unchanged by the treatments, suggesting that the\&nbsp;beneficial effect observed was independent of HbA1c level. IL-6 levels were higher in\&nbsp;eSS and AA, but it remained unaltered in EPA and Wi rats following HNaD diet. Interestingly, EPA protected against serum ROS in rats fed the HNaD, whereas AA did\&nbsp;not. In kidney lysates, ROS decreased significantly in EPA compared to eSS, and\&nbsp;consistently, Nrf-2 expression was higher compared to AA and eSS. Diabetic rats\&nbsp;presented focal segmental sclerosis, adherence to Bowman capsule and mild to\&nbsp;moderate interstitial fibrosis. EPA and AA treatment prevented the kidney damage.\&nbsp;An adequate ω3:ω6 prevents SS in diabetic rats, by a mechanism\&nbsp;independent of glucose metabolism but associated to the prevention of renal oxidative\&nbsp;stress generation. These data suggest that EPA antioxidant properties may prevent the\&nbsp;development of hypertension or kidney damage.},
	url = {https://doi.org/10.1016/j.nut.2019.110644},
	author = {Marianela Vara-Messler and Jorge Humberto Mukdsi and Natalia Osieki and E. Benizio and Gast{\'o}n Repossi and Ebenezer I. O. Ajayi and N{\'e}stor H. Garc{\'\i}a}
}
