title: Ursodeoxycholic Acid Ameliorated Diabetic Nephropathy by Attenuating Hyperglycemia-Mediated Oxidative Stress.
abstract: Oxidative stress has a great role in diabetes and diabetes induced organ damage. Endoplasmic reticulum (ER) stress is involved in the onset of diabetic nephropathy. We hypothesize that ER stress inhibition could protect against kidney injury through anti-oxidative effects. To test whether block ER stress could attenuate oxidative stress and improve diabetic nephropathy in vivo and in vitro, the effect of ursodeoxycholic acid (UDCA), an ER stress inhibitor, on spontaneous diabetic nephropathy db/db mice, ER stress inducer or high glucose-triggered podocytes were studied. Mice were assigned to 3 groups (n=6 per group): control group (treated with vehicle), db/db group (treated with vehicle), and UDCA group (db/db mice treated with 40 mg/kg/d UDCA). After 8 weeks treatment, mice were sacrificed. Blood and kidneys were collected for the assessment of albumin/creatinine ratio, blood urea nitrogen (BUN), serum creatinine (SCr), insulin, total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), oxidized LDL-C, high density lipoprotein cholesterol (HDL-C), non-esterified fatty acid (NEFA), superoxide dismutase (SOD), catalase (CAT), methane dicarboxylic aldehyde (MDA), the expressions of SOD isoforms and glutathione peroxidase 1, as well as histopathological examination. In addition, generation of reactive oxygen species (ROS) was detected by 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence. The results showed that UDCA alleviated renal ER stress-evoked cell death, oxidative stress, renal dysfunction, ROS production, upregulated the expression of Bcl-2 and suppressed Bax in vivo and in vitro. Hence, inhibition ER stress diminishes oxidative stress and exerts renoprotective effects.
authors.affiliation: Laboratory of Renal Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine.
authors.forename: Aili
authors.initials: A
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Hengjiang
authors.initials: H
authors.lastname: Guo
authors.forename: Shuang
authors.initials: S
authors.lastname: Chu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Peng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; C494827:Bax protein, mouse; D001786:Blood Glucose; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D014580:Ursodeoxycholic Acid; D002374:Catalase; D013482:Superoxide Dismutase