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.