title: Branched-chain amino acids attenuate early kidney injury in diabetic rats.
abstract: Diabetic nephropathy (DN) is the most severe diabetic microvascular complication. The pathogenesis of diabetic nephropathy is complex, and oxidative stress plays an important role in the development of diabetic nephropathy. Elevated reactive oxygen species (ROS) levels activate various signaling pathways and influence the activities of transforming growth factor-β (TGF-β) and matrix metalloproteinase-9 (MMP-9), which contributes to glomerular hypertrophy. Branched-chain amino acids (BCAAs) are widely used in clinical treatment, and BCAAs can reduce the oxidative stress associated with the diabetic pancreas and some liver diseases. Thus, the aim of the present study was to determine whether BCAAs could attenuate oxidative stress in the kidneys of streptozotocin (STZ)-induced diabetic rats to prevent early diabetic kidney injury. Male Wistar rats were fed for two weeks with a normal chow diet or a high-fat diet in which 40% of calories were derived from fat. After this two-week period, the mice fed normal chow were injected with vehicle, while the high-fat diet group was injected intraperitoneally (i.p.) with 40 mg/kg STZ. The STZ-treated group was randomly divided into four subgroups that were treated with different doses of BCAAs or vehicle for two months by oral gavage. Plasma glucose, plasma creatinine, urinary protein and JNK, TGF-β, and MMP-9 mRNA and protein expression levels were measured in the rats. The ROS levels and proteinuria in the STZ-induced diabetic rats were significantly higher than those in the control groups. Moreover, early kidney injury occurred in the STZ-induced diabetic rats. However, BCAAs treatment decreased ROS levels, proteinuria and kidney injury. Moreover, JNK, TGF-β and MMP-9 mRNA and protein levels were significantly increased in the diabetic rats when compared with the control rats, and BCAAs treatment reversed these changes. Our results suggest that BCAAs counter oxidative stress in the kidneys of diabetic rats and alleviate diabetic kidney injury via the JNK/TGF-β/MMP-9 pathway.
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated with Shandong University, China; Department of Endocrinology, The Third Hospital of Jinan, Shandong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Mi
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated with Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China.
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine, Zoucheng Traditional Chinese Medicine Hospital, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Endocrinology, The Third Hospital of Jinan, Shandong, China.
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Li
authors.affiliation: Department of Endocrinology, The Third Hospital of Jinan, Shandong, China.
authors.forename: Wei Dong
authors.initials: WD
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Jinan Municipal Authority Clinics, China.
authors.forename: Hui Xia
authors.initials: HX
authors.lastname: Xian
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated with Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, China. Electronic address: qiqimengmi@126.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: D000419:Albuminuria / Q000652:urine; D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D048670:MAP Kinase Kinase 4; D020780:Matrix Metalloproteinase 9
keywords: Branched-chain amino acids; JNK; MMP-9; Streptozotocin; TGF-β