Ursolic acid ameliorates carbon tetrachloride-induced oxidative DNA damage and inflammation in mouse kidney by inhibiting the STAT3 and NF-κB activities.
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.
['Ma|Jie-Qiong|JQ|', 'Ding|Jie|J|', 'Xiao|Zheng-Hua|ZH|', 'Liu|Chan-Min|CM|']
D000818:Animals D000975:Antioxidants D002251:Carbon Tetrachloride D051546:Cyclooxygenase 2 D004249:DNA Damage D007249:Inflammation D020381:Interleukin-17 D015850:Interleukin-6 D007668:Kidney D015227:Lipid Peroxidation D008297:Male D051379:Mice D008813:Mice, Inbred ICR D016328:NF-kappa B D018384:Oxidative Stress D010766:Phosphorylation D017382:Reactive Oxygen Species D051437:Renal Insufficiency D050796:STAT3 Transcription Factor D015398:Signal Transduction D014315:Triterpenes D014409:Tumor Necrosis Factor-alpha
Ursolic acid STAT3 NF-κB Oxidative stress CCl(4) Kidney inflammation