Hesperetin ameliorates diabetic nephropathy in rats by activating Nrf2/ARE/glyoxalase 1 pathway

Autor: Li Kong, Yue Liu, Tao-Yun Wang, Zhuang-Zhuang Tang, Ya-Jing Chen, Yu-Meng Zhang, Yao-Wu Liu
Rok vydání: 2019
Předmět:
Glycation End Products
Advanced
Male
0301 basic medicine
medicine.medical_specialty
NF-E2-Related Factor 2
Glutamate-Cysteine Ligase
Diabetic nephropathy
RM1-950
Kidney
Protective Agents
Streptozocin
Diabetes Mellitus
Experimental
RAGE (receptor)
Rats
Sprague-Dawley
Pathogenesis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Hesperetin
medicine
Animals
Diabetic Nephropathies
Inflammation
Pharmacology
Creatinine
Proteinuria
Hesperidin
Lactoylglutathione Lyase
General Medicine
medicine.disease
Rats
Up-Regulation
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Glyoxalase 1
chemistry
030220 oncology & carcinogenesis
AGEs/RAGE axis
Uric acid
Nrf2/ARE pathway
Therapeutics. Pharmacology
medicine.symptom
Carboxylic Ester Hydrolases
Signal Transduction
Zdroj: Biomedicine & Pharmacotherapy, Vol 111, Iss, Pp 1166-1175 (2019)
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2019.01.030
Popis: Diabetic nephropathy (DN) is one of the most common diabetic complications, and alpha-carbonyl aldehydes and their detoxicating enzyme glyoxalase 1 (Glo-1) play vital roles in pathogenesis of diabetic complications. The aim of this study was to evaluate the renoprotective effects of hesperetin against DN in rats, and to investigate mechanisms from the aspect of Nrf2/ARE/Glo-1 pathway. Streptozotocin-induced diabetic rats were treated orally with hesperetin (50 and 150 mg/kg), or nuclear factor erythroid-derived-2-like 2 (Nrf2) inducer tert-butylhydroquinone (tBHQ, 25 mg/kg) for 10 weeks. Then proteinuria, creatinine, urea nitrogen, and uric acid were assayed for renal functions, fibronectin and collagen IV levels by immunohistochemistry, as well as periodic acid-Schiff staining and electron microscope observation, were used to assess renal morphology. Glo-1 activity, protein, and mRNA levels and the classic Nrf2/ARE pathway were investigated. Moreover, advanced glycation endproducts (AGEs) and its receptor RAGE, interleukin-1β and tumor necrosis factor-α levels were also examined in the kidney. Hesperetin markedly ameliorated the renal functions and structural changes of diabetic rats, accompanied by up-regulation of Glo-1 as well as inhibition of AGEs/RAGE axis and inflammation. Meanwhile, hesperetin caused significant increases in Nrf2 and p-Nrf2 levels, as well as up-regulation of γ-glutamylcysteine synthetase, a well-known target gene of Nrf2/ARE signaling. Our results demonstrated that hesperetin could slow down the pathological process of DN, and Glo-1 enhancement contributed to the beneficial effects, which was obtained by the activation of Nrf2/ARE pathway.
Databáze: OpenAIRE
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