Cargando…

Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells

Lead (Pb) is an important environmental pollutant. Oxidative stress and the inflammatory response have been postulated as mechanisms involved in lead-induced renal damage. Smilax glabra Roxb. has been used for treatment of heavy-metal poisoning in China for 500 years. We investigated S. glabra flavo...

Descripción completa

Detalles Bibliográficos
Autores principales: Shi, Yueyue, Tian, Chongmei, Yu, Xinfen, Fang, Yuejuan, Zhao, Xinyu, Zhang, Xiaoxi, Xia, Daozong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493636/
https://www.ncbi.nlm.nih.gov/pubmed/32982754
http://dx.doi.org/10.3389/fphar.2020.556248
_version_ 1783582599211384832
author Shi, Yueyue
Tian, Chongmei
Yu, Xinfen
Fang, Yuejuan
Zhao, Xinyu
Zhang, Xiaoxi
Xia, Daozong
author_facet Shi, Yueyue
Tian, Chongmei
Yu, Xinfen
Fang, Yuejuan
Zhao, Xinyu
Zhang, Xiaoxi
Xia, Daozong
author_sort Shi, Yueyue
collection PubMed
description Lead (Pb) is an important environmental pollutant. Oxidative stress and the inflammatory response have been postulated as mechanisms involved in lead-induced renal damage. Smilax glabra Roxb. has been used for treatment of heavy-metal poisoning in China for 500 years. We investigated S. glabra flavonoids extract (SGF) could attenuate lead acetate-induced nephrotoxicity in weaning rats and human embryonic kidney (HEK)-293 cells, and investigated the possible mechanisms. Compared with Pb exposed group of weaning rats, SGF could significantly promote lead excretion in the blood and kidney, and increase the content of the renal-function indicators blood urea nitrogen, serum uric acid, and serum creatinine. SGF could improve the glomerular filtration rate (GFR) and histologic changes in the kidneys of weaning rats exposed to Pb. SGF could also reduce lead-induced cytotoxicity, improve DNA damage-induced apoptosis and cleaved caspase-3-mediated apoptosis in HEK-293 cells stimulated with Pb. SGF significantly increased the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase, and decreased excessive release of reactive oxygen species (ROS) and malondialdehyde in the kidneys of the weaning rats and in HEK-293 cells. The antioxidant mechanism of SGF related to activation of the Kelch-like ECH-associated protein 1/nuclear-factor-E2-related factor 2/hemeoxygenase-1(Keap1/Nrf2/HO-1) pathway. SGF could inhibit secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α induced by Pb in vivo and in vitro. The anti-inflammatory mechanism of SGF related to inhibition of ROS and pro-inflammatory cytokines triggered the nuclear factor-kappa B (NF-κB) pathway through blockade of inhibitors of I-κB degradation, phosphorylation of NF-κB p65, and nuclear translocation of p65. Our findings indicate that SGF could be a natural antioxidant and anti-inflammatory agent for treating lead-induced nephrotoxicity.
format Online
Article
Text
id pubmed-7493636
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-74936362020-09-24 Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells Shi, Yueyue Tian, Chongmei Yu, Xinfen Fang, Yuejuan Zhao, Xinyu Zhang, Xiaoxi Xia, Daozong Front Pharmacol Pharmacology Lead (Pb) is an important environmental pollutant. Oxidative stress and the inflammatory response have been postulated as mechanisms involved in lead-induced renal damage. Smilax glabra Roxb. has been used for treatment of heavy-metal poisoning in China for 500 years. We investigated S. glabra flavonoids extract (SGF) could attenuate lead acetate-induced nephrotoxicity in weaning rats and human embryonic kidney (HEK)-293 cells, and investigated the possible mechanisms. Compared with Pb exposed group of weaning rats, SGF could significantly promote lead excretion in the blood and kidney, and increase the content of the renal-function indicators blood urea nitrogen, serum uric acid, and serum creatinine. SGF could improve the glomerular filtration rate (GFR) and histologic changes in the kidneys of weaning rats exposed to Pb. SGF could also reduce lead-induced cytotoxicity, improve DNA damage-induced apoptosis and cleaved caspase-3-mediated apoptosis in HEK-293 cells stimulated with Pb. SGF significantly increased the activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase and catalase, and decreased excessive release of reactive oxygen species (ROS) and malondialdehyde in the kidneys of the weaning rats and in HEK-293 cells. The antioxidant mechanism of SGF related to activation of the Kelch-like ECH-associated protein 1/nuclear-factor-E2-related factor 2/hemeoxygenase-1(Keap1/Nrf2/HO-1) pathway. SGF could inhibit secretion of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α induced by Pb in vivo and in vitro. The anti-inflammatory mechanism of SGF related to inhibition of ROS and pro-inflammatory cytokines triggered the nuclear factor-kappa B (NF-κB) pathway through blockade of inhibitors of I-κB degradation, phosphorylation of NF-κB p65, and nuclear translocation of p65. Our findings indicate that SGF could be a natural antioxidant and anti-inflammatory agent for treating lead-induced nephrotoxicity. Frontiers Media S.A. 2020-09-02 /pmc/articles/PMC7493636/ /pubmed/32982754 http://dx.doi.org/10.3389/fphar.2020.556248 Text en Copyright © 2020 Shi, Tian, Yu, Fang, Zhao, Zhang and Xia http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Shi, Yueyue
Tian, Chongmei
Yu, Xinfen
Fang, Yuejuan
Zhao, Xinyu
Zhang, Xiaoxi
Xia, Daozong
Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells
title Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells
title_full Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells
title_fullStr Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells
title_full_unstemmed Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells
title_short Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells
title_sort protective effects of smilax glabra roxb. against lead-induced renal oxidative stress, inflammation and apoptosis in weaning rats and hek-293 cells
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493636/
https://www.ncbi.nlm.nih.gov/pubmed/32982754
http://dx.doi.org/10.3389/fphar.2020.556248
work_keys_str_mv AT shiyueyue protectiveeffectsofsmilaxglabraroxbagainstleadinducedrenaloxidativestressinflammationandapoptosisinweaningratsandhek293cells
AT tianchongmei protectiveeffectsofsmilaxglabraroxbagainstleadinducedrenaloxidativestressinflammationandapoptosisinweaningratsandhek293cells
AT yuxinfen protectiveeffectsofsmilaxglabraroxbagainstleadinducedrenaloxidativestressinflammationandapoptosisinweaningratsandhek293cells
AT fangyuejuan protectiveeffectsofsmilaxglabraroxbagainstleadinducedrenaloxidativestressinflammationandapoptosisinweaningratsandhek293cells
AT zhaoxinyu protectiveeffectsofsmilaxglabraroxbagainstleadinducedrenaloxidativestressinflammationandapoptosisinweaningratsandhek293cells
AT zhangxiaoxi protectiveeffectsofsmilaxglabraroxbagainstleadinducedrenaloxidativestressinflammationandapoptosisinweaningratsandhek293cells
AT xiadaozong protectiveeffectsofsmilaxglabraroxbagainstleadinducedrenaloxidativestressinflammationandapoptosisinweaningratsandhek293cells