title: Ursolic acid ameliorates carbon tetrachloride-induced oxidative DNA damage and inflammation in mouse kidney by inhibiting the STAT3 and NF-κB activities.
abstract: Ursolic acid (UA), a common pentacyclic triterpenoid compound, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced injury in kidneys are not yet clear. In the current report, we investigated whether UA inhibited the oxidative stress and inflammation in the kidneys of CCl4 treated mice. Male ICR mice were injected with CCl4 with or without UA co-administration (25 and 50mg/kg intragastrically once daily) for six weeks. Our data showed that UA significantly prevented CCl4-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage and histopathological analysis. Moreover, CCl4-induced profound elevation of ROS and oxidative stress, as evidenced by the increase of lipid peroxidation level and the depletion of the total antioxidant capacity (TAC) level in the kidney, was suppressed by treatment with UA. UA also decreased 8-hydroxy-2-deoxyguanosine (one product of oxidative DNA damage) levels. Furthermore, protein expression by Western blot analysis showed that UA significantly decreased production of pro-inflammatory markers including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-17 (IL-17) and cyclooxygenase-2 (COX-2) in CCl4-treated mouse kidney. In exploring the underlying mechanisms of UA action, we found that UA increased the phosphorylation of transcription 3 (STAT3), which in turn activated the nuclear factor kappa B (NF-kappaB) and the inflammatory cytokines in the kidneys. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by UA is due at least in part to its anti-oxidant activity and its ability to modulate the STAT3 and NF-κB signaling pathways.
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, 643000 Zigong City, Sichuan Province, PR China. Electronic address: a1032042419@126.com.
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Ma
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, 643000 Zigong City, Sichuan Province, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Sichuan University of Science and Engineering, 643000 Zigong City, Sichuan Province, PR China.
authors.forename: Zheng-Hua
authors.initials: ZH
authors.lastname: Xiao
authors.affiliation: School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tangshan New Area, 221116 Xuzhou City, Jiangsu Province, PR China.
authors.forename: Chan-Min
authors.initials: CM
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D000975:Antioxidants; D002251:Carbon Tetrachloride; D051546:Cyclooxygenase 2; D020381:Interleukin-17; D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000097245:Ursolic Acid; C494087:Stat3 protein, mouse
keywords: CCl(4); Kidney inflammation; NF-κB; Oxidative stress; STAT3; Ursolic acid