title: Protective Effects of Quercetin Against HgCl₂-Induced Nephrotoxicity in Sprague-Dawley Rats.
abstract: Mercury is a well-known environmental pollutant that can cause nephropathic diseases, including acute kidney injury (AKI). Although quercetin (QC), a natural flavonoid, has been reported to have medicinal properties, its potential protective effects against mercury-induced AKI have not been evaluated. In this study, the protective effect of QC against mercury-induced AKI was investigated using biochemical parameters, new protein-based urinary biomarkers, and a histopathological approach. A 250 mg/kg dose of QC was administered orally to Sprague-Dawley male rats for 3 days before administration of mercury chloride (HgCl2). All animals were sacrificed at 24 h after HgCl2 treatment, and biomarkers associated with nephrotoxicity were measured. Our data showed that QC absolutely prevented HgCl2-induced AKI, as indicated by biochemical parameters such as blood urea nitrogen (BUN) and serum creatinine (sCr). In particular, QC markedly decreased the accumulation of Hg in the kidney. Urinary excretion of protein-based biomarkers, including clusterin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular endothelial growth factor (VEGF) in response to HgCl2 administration were significantly decreased by QC pretreatment relative to that in the HgCl2-treated group. Furthermore, urinary excretion of metallothionein and Hg were significantly elevated by QC pretreatment. Histopathological examination indicated that QC protected against HgCl2-induced proximal tubular damage in the kidney. A TUNEL assay indicated that QC pretreatment significantly reduced apoptotic cell death in the kidney. The administration of QC provided significant protective effects against mercury-induced AKI.
authors.affiliation: 1 College of Pharmacy, Pusan National University , Busan, South Korea .
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Shin
authors.forename: Jeong Jun
authors.initials: JJ
authors.lastname: Kim
authors.forename: Ye Ji
authors.initials: YJ
authors.lastname: Kim
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.forename: In Young
authors.initials: IY
authors.lastname: Kim
authors.forename: Han-Seung
authors.initials: HS
authors.lastname: Shin
authors.forename: Kyeong Seok
authors.initials: KS
authors.lastname: Kim
authors.forename: Eui-Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Kyu Hyuck
authors.initials: KH
authors.lastname: Chung
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.forename: Hyung Sik
authors.initials: HS
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000378:metabolism / Q000633:toxicity*; D020011:Protective Agents / Q000008:administration & dosage*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015815:Cell Adhesion Molecules; D000071068:Lipocalin-2; D054834:Lipocalins; D008627:Mercuric Chloride; D020011:Protective Agents; D011518:Proto-Oncogene Proteins; D011794:Quercetin; D042461:Vascular Endothelial Growth Factor A; C110936:Havcr1 protein, rat; C097278:Lcn2 protein, rat
keywords: acute kidney injury; mercury; metallothionein; protective effect; quercetin