The protective effect and mechanism of ellagic acid on liver injury induced by titanium dioxide nanoparticles
Objective To explore the protective mechanism of ellagic acid(EA)on liver injury induced by nano titanium dioxide particles(TiO2 NPs).Methods 40 mice were randomly divided into Control group,EA group,TiO2 NPs group and TiO2 NPs+EA group.The Control group did not receive any treatment.The TiO2 NPs group received TiO2 NPs 150 mg/(kg·d)by gavage,the EA group received EA 50 mg/(kg·d),and the TiO2 NPs+EA group received EA 50 mg/(kg·d)by gavage on the basis of TiO2 NPs 150 mg/(kg·d)ad-ministration.8 weeks later,the liver injury indexes were detected,and the pathological changes of liver tissue were observed.Western blot was used to detect the expression of oxidative stress-related Ogg1,lipid synthesis re-lated Srebp-1c,and endoplasmic reticulum stress-related Bip,Pdi,ATF6-p50,ATF6-p90,p-Ire1α,Xbp1s,xbp1u,p-elf2α,ATF4,and liver fibrosis related α-SMA expression in each group.qRCR was used to detect the mRNA levels of maintaining lipid metabolism homeostasis related Acox2,Ces1g,Acot7,Cpt1a,Scad,Srebf1,Mlxipl,Lxrα,Xbp1s,endoplasmic reticulum stress related Atf4,Chop and liver fibrosis related Tgfb,Col1α1 and α-Sma in each group.Results Compared with the Control group,the liver index of mice in TiO2 NPs group increased.The liver structure was disordered.The expression of Ogg1,Srebp-1c,Bip,ATF6-p50,ATF6-p90,p-Ire1α,Xbp1s,xbp1u,p-eIf2α,ATF4 and α-SMA significantly increased.The mRNA levels of Acox2,Ces1g,Acot7,Cpt1a,Scad significantly decreased,while Pparα,Srebf1,Mlxipl,Lxrα,Xbp1s,Atf4,Chop,Tgfb,Col1α1 and α-Sma expression significantly increased.Compared with the TiO2 NPs group,the above indi-cators of mice in the TiO2 NPs+EA group showed recovery towards Control.Conclusion EA relieves TiO2 NPs induced liver injury by alleviating oxidative stress,endoplasmic reticulum stress and lipid metabolism disorder.
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