Dietary n-3 polyunsaturated fatty acids revert renal responses induced by a combination of 2 protocols that increase the amounts of advanced glycation end product in rats

Abstract

Renal dysfunction is a severe complication that is caused by diabetes mellitus. Many factors associate the progression of this complication with high levels of proinflammatory and pro-oxidant substances, such as advanced glycation end products (AGEs), which form a heterogeneous group of compounds that can accumulate in tissues such as retinas, joints, and kidneys. The hypothesis of this study is that n-3 polyunsaturated fatty acids (n-3 PUFAs) have a nephroprotective effect on rats after exposing them to a combination of 2 protocols that increase the AGE amounts: a high-fat diet enriched with AGEs and a diabetes rat model. Adult Wistar rats were divided into 6 groups that received the following diets for 4 weeks: (1) control group; 2) HAGE: high AGE fat-containing diet group; (3) HAGE + n-3: high AGE fat-containing diet plus n-3 PUFAs group; (4) diabetic group; (5) Db + HAGE: high AGE fat-containing diet diabetic group; and (6) Db + HAGE + n-3: high AGE fat-containing diet plus n-3 PUFAs diabetic group. Diabetes mellitus was induced by an intraperitoneal injection of alloxan (150 mg kg(-1)). In diabetic and nondiabetic rats, the high HAGE fat-containing diet increased the serum creatinine, tumor necrosis factor-α, thiobarbituric acid reactive substances, and reactive oxygen species levels, as well as the superoxide dismutase/catalase + glutathione peroxidase ratio and the superoxide dismutase 2 and receptor for advanced glycation end products immunocontent of the kidneys. n-3 Polyunsaturated fatty acids attenuated these alterations and influenced the receptor for advanced glycation end products/oxidative stress/tumor necrosis factor-α axis. In summary, this study showed that the extrinsic AGE pathway (HAGE diet) had a greater effect on renal metabolism than the intrinsic AGE pathway (diabetes induction) and that n-3 PUFAs appear to prevent renal dysfunction via antioxidant and anti-inflammatory pathways.

Dietary fat quantity and quality modifies advanced glycation end products metabolism in patients with metabolic syndrome

“…Also PUFA have been associated with anti‐inflammatory effects . Indeed, a recent study observed that dietary supplementation of n‐3 PUFA appears to prevent renal dysfunction on diabetic rats after exposing them to high levels of AGE, via antioxidant and anti‐inflammatory pathways . Our data suggest that both low‐fat diets (LFHCC and LFHCC n‐3) provide a healthy effect on MetS patients compared to HSFA diet, but show an intermediate effect regarding to AGE content, compared to the HMUFA diet.…”

Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression

“…The renal protective effect for n-3 PUFAs is inconsistency among the diet manipulation studies. Many epidemiologic and animal studies show the correlation of n-3 PUFAs deficiency and CKD progression151617181920. And PUFAs may interfere with renal fibrogenesis via inhibiting pro-inflammatory cytokine production as well as renin and nitric oxide (NO) systems21.…”

Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats

“…The optimal dosage regimen for intraperitoneally administered alloxan is a single high dose between 150 and 200 mg/kg (Federiuk et al, 2004; de Assis et al, 2015). Although most rats developed type-1 DM after administration of alloxan, a few rats developed type-2 DM, characterized by stable high blood glucose values, with normal ketone concentration (Federiuk et al, 2004).…”

“…Proteins (20 μg) were separated by SDS-PAGE on 10% (w/v) acrylamide and 0.275% (w/v) bisacrylamide gels and then electrotransferred onto nitrocellulose membranes according to (de Assis et al, 2015). Membranes were incubated for 12 h with the appropriate primary antibody (MCT1, 1:800; MCT2, 1:600; Pierre et al, 2000) and β-tubulin, 1:2000 (Santa Cruz Biotechnology, Heidelberg, Germany).…”