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...
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| Format: | Article |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.556248/full |
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| author | Yueyue Shi Chongmei Tian Chongmei Tian Xinfen Yu Yuejuan Fang Xinyu Zhao Xiaoxi Zhang Daozong Xia |
| author_facet | Yueyue Shi Chongmei Tian Chongmei Tian Xinfen Yu Yuejuan Fang Xinyu Zhao Xiaoxi Zhang Daozong Xia |
| author_sort | Yueyue Shi |
| collection | DOAJ |
| 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. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T22:52:18Z |
| publishDate | 2020-09-01 |
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| spelling | doaj.art-d3f27ca332ee4c1081f3c2c3e00f9e5c2022-12-21T22:44:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-09-011110.3389/fphar.2020.556248556248Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 CellsYueyue Shi0Chongmei Tian1Chongmei Tian2Xinfen Yu3Yuejuan Fang4Xinyu Zhao5Xiaoxi Zhang6Daozong Xia7College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Pharmacy, Affiliated Shaoxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Shaoxing, ChinaCenter of Health Laboratory Technology, Hangzhou Center for Disease Control and Prevention, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaLead (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.https://www.frontiersin.org/article/10.3389/fphar.2020.556248/fullSmilax glabra Roxb.lead-induced nephrotoxicityapoptosisoxidative stressinflammatory pathway |
| spellingShingle | Yueyue Shi Chongmei Tian Chongmei Tian Xinfen Yu Yuejuan Fang Xinyu Zhao Xiaoxi Zhang Daozong Xia Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells Frontiers in Pharmacology Smilax glabra Roxb. lead-induced nephrotoxicity apoptosis oxidative stress inflammatory pathway |
| 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 | Smilax glabra Roxb. lead-induced nephrotoxicity apoptosis oxidative stress inflammatory pathway |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.556248/full |
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