Renal Oxidation of ESS diabetic rats is minimized by EPA

Abstract

Salt sensitivity (SS) is associated with increased cardiovascular risk in diabetic patients. This abnormal mechanism results in an increased renal oxydation and decreased urinary sodium excretion and if it is maintained over time can develop hypertension and its complications. Currently the Western diet has limited content of polyunsaturated fatty acids, with antioxidant capacity such as ecoisapentaneoico acid (EPA). Therefore we hypothesized that nutritional supplementation with EPA, prevents SS in DM rats by decreasing renal oxidative stress. Our objectives were; to asses SS of eSS diabetic rats and to investigate the ability of EPA to prevent SS in these rats.MethodsWistar rats were used as healthy controls. Type II diabetic rat group (eSS), 3 months old, were divided in 3 groups, diabetic control (eSS), eSS treated with arachidonic acid (pro‐oxidant)(2.5mg / ip, per month) (eSS + AA) and eSS treated with EPA (2.5mg / ip per month) (eSS + EPA). Animals were treated during 1 year, then placed in metabolic cages and subsequently underwent 2 experimental periods of 7 days each with normal sodium diet (0.4% NaCl)(NNaD) and high salt diet (4% NaCl)(HNaD). At the end of each period weight, systolic blood pressure (SBP), HbA1c, triglycerides (Trig), cholesterol (Chol), creatinine (Cre), kidney γ‐glutamyl transpeptidase activity (γGTP)​​, urinary protein excretion (UprotV).ResultseSS rats had elevated HbA1c, Tri, Chol and reduced body weight vs. Wistar control group. Renal function was normal during the experimental period. The eSS + AA group also showed elevation of HbA1c, Trig, with no change in Cre and Chol. During NNaD SBP was 119 ± 3 mmHg and after HNaD 125 ± 1 mmHg (p <0.05). In contrast, EPA + eSS lowered HbA1c (5.6 ± 0.3% vs 7.0 ± 0.2%, p <0.05), Trig (175±1 mg/dl vs 245±12 mg/dl p <0.05), and increased body weight (424±11 g vs 511±22gr, p <0.05) vs eSS. EPA supplement prevented the increase of SBP during the HNaD (126±2 mmHg vs. 128±2 mmHg p> 0.5). eSS + AA did not differ from eSS group. No significant difference was observed in UprotV between groups. Urinary sodium excretion increased with HNAD. Renal interstitium γ‐GT activity in eSS group was 0.65±0.04 au and 0.61±0.02 au in eSS + AA group, while in EPA + eSS 0.5±0.03 (p <0.05).ConclusionThe salt sentitive eSS rats have hypertriglyceridemia and elevated HbA1c. Nutritional supplementation with EPA prevented the salt sensitivity, the increased of HbA1c and triglycerides. These changes were associated with lower kidney γ‐GT ​​activity, suggesting that the EPA dietary supplement can be used in diabetic patients to prevent salt sensitivity and improve metabolic abnormalities.