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24‐week exposure to dietary oxidized tyrosine (O‐Tyr) induces renal injury in rats through activation of p38 signaling
Author(s) -
Li Zhuqing,
Shi Yonghui,
Le Guowei,
Ding Yinyi,
Zhao Qi,
Tang Xue
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb225
Subject(s) - oxidative stress , chemistry , endocrinology , superoxide dismutase , kidney , malondialdehyde , medicine , blood urea nitrogen , glutathione peroxidase , biochemistry
Oxidized tyrosine (O‐Tyr) products such as Dityrosine (Dityr) and 3‐nitrotyrosine (3‐NT) have been widely detected in many commercial protein products. Since dietary O‐Tyr has been demonstrated to induce health harmful effects in our previous study, the objective of the present study was to examine renal toxicity of dietary O‐Tyr, focusing on oxidative stress and fibrosis changes. Male Sprague‐Dawley (SD) rats were treated with 0, 2, 4 and 8 g O‐Tyr/kg diet each day for 24 weeks. A group of rats treated with 8 g Tyr/kg diet were set as Tyr control. The kidney index, urine volume (UV), serum creatinine (Scr), blood urea nitrogen (BUN) and oxidative stress indexes were tested to evaluate renal injury. Expression of extra cellular matrix (ECM) contents, including hyaluronic acid (HA), laminin (LN), procollagen type Icarboxy terminal peptide (ICTP) and type I procollagen peptide (PINP), together with Masson staining of kidney slices was tested to investigate renal fibrosis. mRNA and protein expression related to p38 pathway was detected using the method of quantitative real‐time reverse transcription PCR, western blot and immunohistochemical staining. Our results showed that 24‐week feeding of O‐Tyr elevated kidney index, UV, Scr and BUN levels. Renal oxidative stress was evidenced by increased levels of ROS, protein carbonyl (PC), Dityr, 3‐NT, advanced oxidative protein products (AOPPs), malondialdehyde (MDA) and decreased activities of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT). The expression of transforming growth factor‐β (TGF‐β), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β) and IL‐6 in the kidneys increased after O‐Tyr treatment, suggesting renal inflammation. O‐Tyr also distinctly increased the phosphorylation of p38, enhanced fibrosis‐related TGF‐β1 and Smad 2/3 expression. In addition, elevated ECM contents, including HA, LN, ICTP and PINP, accompanied with results of Masson staining also supported renal fibrosis changes. All these changes are dose‐dependent in O‐Tyr treated group. Overall, our results suggested that O‐Tyr induces renal oxidative stress and renal fibrosis, which may be mediated through the activation of p38 signaling. Support or Funding Information The present study was supported by the 12th Five‐Year Plan for for Science and Technology Development (No. 2012BAD33B05)