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Title: Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

Abstract

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500 mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400 mg PU/kg intragastrically once daily) for 75 days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt,more » phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. Highlights: ► Puerarin prevented lead-induced nephrototoxicity. ► Puerarin reduced lead-induced increase in ROS and TBARS production in kidney of rats. ► Puerarin activated the PI3K/Akt/eNOS pathway in kidney. ► Puerarin regulated the expression of pro-apoptotic proteins and caspase activation. ► Puerarin significantly inhibited the lead-induced apoptosis in rat kidney.« less

Authors:
 [1];  [2];  [1]
  1. School of Life Science, Xuzhou Normal University, No.101, Shanghai Road, Tangshan New Area, Xuzhou City 221116, Xuzhou City, Jiangsu Province (China)
  2. School of Chemical Engineering, China University of Mining and Technology, Xuzhou 221008, Xuzhou City, Jiangsu Province (China)
Publication Date:
OSTI Identifier:
22215226
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 258; Journal Issue: 3; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; ANTIOXIDANTS; APOPTOSIS; BIOLOGICAL RECOVERY; CREATININE; DRINKING WATER; GLUTATHIONE; INHIBITION; INJURIES; KIDNEYS; LIPIDS; MITOCHONDRIA; NITRIC OXIDE; OXIDATION; OXYGEN; RATS; UREA; URIC ACID

Citation Formats

Liu, Chan-Min, Ma, Jie-Qiong, and Sun, Yun-Zhi. Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2011.11.015.
Liu, Chan-Min, Ma, Jie-Qiong, & Sun, Yun-Zhi. Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. United States. https://doi.org/10.1016/J.TAAP.2011.11.015
Liu, Chan-Min, Ma, Jie-Qiong, and Sun, Yun-Zhi. 2012. "Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway". United States. https://doi.org/10.1016/J.TAAP.2011.11.015.
@article{osti_22215226,
title = {Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway},
author = {Liu, Chan-Min and Ma, Jie-Qiong and Sun, Yun-Zhi},
abstractNote = {Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500 mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400 mg PU/kg intragastrically once daily) for 75 days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt, phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. Highlights: ► Puerarin prevented lead-induced nephrototoxicity. ► Puerarin reduced lead-induced increase in ROS and TBARS production in kidney of rats. ► Puerarin activated the PI3K/Akt/eNOS pathway in kidney. ► Puerarin regulated the expression of pro-apoptotic proteins and caspase activation. ► Puerarin significantly inhibited the lead-induced apoptosis in rat kidney.},
doi = {10.1016/J.TAAP.2011.11.015},
url = {https://www.osti.gov/biblio/22215226}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 258,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2012},
month = {Wed Feb 01 00:00:00 EST 2012}
}