GSPE reduces lead-induced oxidative stress by activating the Nrf2 pathway and suppressing miR153 and GSK-3β in rat kidney.
Lead (Pb) is a global environmental health hazard that leads to nephrotoxicity. However, the effective treatment of Pb-induced nephrotoxicity remains elusive. Grape seed procyanidin extract (GSPE) has beneficial properties for multiple biological functions. Therefore, the present study investigated whether GSPE reduced Pb-induced nephrotoxicity as well as the protective mechanism of GSPE in a well-established 35-day Pb induced nephrotoxicity rat model. The results showed that GSPE normalized Pb-induced oxidative stress, histological damage, inflammatory, apoptosis, and changes of miR153 and glycogen synthase kinase 3β (GSK-3β) levels in rat kidney. Moreover, GSPE enhanced the induction of phase II detoxifying enzymes (heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1) by increasing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. This study identifies for the first time that Pb-induced oxidative stress in rat kidney is attenuated by GSPE treatment via activating Nrf2 signaling pathway and suppressing miR153 and GSK-3β. Nrf2 signaling provides a new therapeutic target for renal injury induced by Pb, and GSPE could be a potential natural agent to protect against Pb-induced nephrotoxicity.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Biying
B
Liu
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Haili
H
Zhang
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Xiao
X
Tan
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Daqian
D
Yang
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Zhanjun
Z
Lv
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Huijie
H
Jiang
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Jingjing
J
Lu
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Ruiqi
R
Baiyun
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.
Zhigang
Z
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D044946:Biflavonoids / Q000494:pharmacology*; D015415:Biomarkers; D002392:Catechin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D056604:Grape Seed Extract / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007854:Lead / Q000494:pharmacology* / Q000633:toxicity; D035683:MicroRNAs / Q000235:genetics*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D044945:Proanthocyanidins / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D044946:Biflavonoids; D015415:Biomarkers; D056604:Grape Seed Extract; C000606654:MIRN153 microRNA, rat; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D044945:Proanthocyanidins; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D007854:Lead; C017674:procyanidin; D002392:Catechin; D000071679:Glycogen Synthase Kinase 3 beta
Nrf2; grape seed procyanidin extract; kidney injury; nephroprotective effect; oxidative stress