title: Puerarin ameliorates carbon tetrachloride-induced oxidative DNA damage and inflammation in mouse kidney through ERK/Nrf2/ARE pathway.
abstract: Puerarin (PU), a natural flavonoid, has been shown to possess many benefits and medicinal properties. In this study, we evaluated the effect of puerarin on oxidative stress and inflammation in kidney induced by carbon tetrachloride (CCl4) and explored the potential mechanisms underlying this effect. Our results showed that puerarin administration significantly inhibited CCl4-induced kidney injury, which indicated by both diagnostic indicators and histopathological analysis. One of the potential mechanisms of puerarin action was decreased the oxidative stress, as evidenced by decreasing of lipid peroxidation level, increasing of SOD, CAT and GPx activities and GSH level. Puerarin also decreased 8-hydroxy-2-deoxyguanosine (one product of oxidative DNA damage) level and increased the expression levels of NQO1, GST and HO-1 in kidneys of CCl4-treated mice. Moreover, western blot analysis showed that puerarin decreased production of pro-inflammatory markers including iNOS and COX-2 in CCl4-treated mouse kidney. We found that puerarin significantly inhibited the ERK phosphorylation and increased the translocation of Nrf2 from the cytosol to the nuclear fraction, which in turn inactivated NF-κB and the inflammatory cytokines in kidneys of the CCl4-treated mice. Altogether, these results suggest that puerarin could protect the CCl4-induced oxidative stress and inflammation by ERK/Nrf2/ARE pathway.
authors: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China. Electronic address: a1032042419@126.com.
authors: Jie-Qiong
authors: JQ
authors: Ma
authors: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China.
authors: Jie
authors: J
authors: Ding
authors: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, No. 180, Huixing Road, 643000 Zigong City, Sichuan Province, PR China.
authors: Zheng-Hua
authors: ZH
authors: Xiao
authors: School of Life Science, Jiangsu Normal University, No.101, Shanghai Road, Tongshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors: Chan-Min
authors: CM
authors: Liu
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D007529:Isoflavones; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D002251:Carbon Tetrachloride; D048049:Extracellular Signal-Regulated MAP Kinases; C033607:puerarin
keywords: Carbon tetrachloride; ERK; Inflammation; Nrf2; Oxidative stress; Puerarin