Omega-3 polyunsaturated fatty acids alleviate adenine-induced chronic renal failure via regulating ROS production and TGF-β/SMAD pathway

J. Xu, Z.-P. Feng, H.-Y. Peng, P. Fu

Kidney Research Institute, Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China. fupinghx@scu.edu.cn

---

• Pharmacology

OBJECTIVE: To explore the role of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in adenine-induced rat chronic renal failure and its underlying mechanism.

MATERIALS AND METHODS: 30 Sprague Dawley (SD) rats were randomly assigned into three groups, namely sham group, adenine induction group (adenine group) and adenine induction + ω-3 PUFAs treatment group (ω-3 PUFAs group), with 10 rats in each group. Serum and kidney samples were collected after rats were sacrificed. Serum levels of Cr (creatinine) and BUN (urea nitrogen) were detected using commercial kits. HE (hematoxylin and eosin) staining was performed to evaluate the pathological changes of kidneys. Levels of oxidative stress indicators in rat kidney homogenate were detected by relative commercial kits, including SOD (superoxide dismutase), GSH (reduced glutathione), CAT (catalase), and T-AOC (total antioxidant capacity). Reactive oxygen species (ROS) production was also detected by immunofluorescence. Protein expressions of nuclear factor E2 related factor 2 (Nrf2) and transforming growth factor-beta (TGF-β)/SMAD pathway-related genes were detected by Western blot.

RESULTS: Serum levels of Cr and BUN in ω-3 PUFAs group were remarkably decreased compared with those of adenine group. Higher contents of SOD, GSH, CAT and T-AOC were observed in ω-3 PUFAs group compared with those of adenine group. Besides, MAD content and ROS production were lower in ω-3 PUFAs group than those of adenine group. Pathological changes of kidneys were alleviated after ω-3 PUFAs treatment. Western blot results demonstrated that ω-3 PUFAs treatment remarkably upregulates Nrf2, HO-1, NQO1, but downregulates relative genes in TGF-β/SMAD pathway.

CONCLUSIONS: ω-3 PUFAs alleviated adenine-induced chronic renal failure through enhancing antioxidant stress and inhibiting inflammatory response via regulating Nrf2 and TGF-β/SMAD pathway.

This article has been retracted. The Publisher apologizes for any inconvenience this may cause.

Free PDF Download