纳米二氧化钛经口暴露对小鼠肝脏的影响
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摘要
目的探讨纳米二氧化钛(Ti O2NPs)经口暴露后对小鼠肝脏的影响。方法 60只健康雄性ICR小鼠随机分为对照组、TiO_2 NPs (10、50、100) mg/kg·BW染毒组,连续灌胃30 d后,颈椎脱臼处死小鼠,计算小鼠肝脏系数,观察小鼠肝脏组织病理学切片,测定肝组织匀浆中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST),超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、总抗氧化能力(T-AOC)活力以及丙二醛(MDA)含量。结果与对照组相比,各染毒组小鼠肝脏系数差异无统计学意义(P>0.05);病理学切片观察各染毒组肝脏组织均可见不同程度肝组织损伤;随着TiO_2 NPs染毒剂量的增加,ALT、AST活力以及MDA含量在50、100 mg/kg·BW组升高,SOD活性在100 mg/kg·BW组降低,GSHPX活性在50、100 mg/kg·BW组降低,T-AOC水平在10、50、100 mg/kg·BW组均降低,差异均具有统计学意义(P<0.05)。结论经口暴露TiO_2 NPs,可使小鼠肝脏发生氧化应激反应,造成肝脏氧化损伤,并最终导致小鼠肝脏组织结构及功能破坏,具有一定的肝脏毒性作用。
Objective The research was performed to explore the effect of titanium dioxide nanoparticles(TiO_2 NPs) on liver after oral exposure to in mice. Methods 60 healthy male ICR mice were randomly divided into control group and TiO_2 NPs(10,50,100) mg/kg·BW groups. The mice were exposed to TiO_2 NPs via intragastric administration for 30 days.The liver coefficient, liver histopathology, alanine aminotransferase(ALT), aspartate aminotransferase(AST), superoxide dismutase(SOD),glutathione peroxidase(GSH-PX), total antioxidant capacity(T-AOC) activity and malondialdehyde(MDA) content were assessed after the mice were killed. Results The difference was not statistically significant of liver coefficient among TiO_2 NPs exposed groups compared with that of control group(P>0.05). Histopathological sections were observed that the liver tissue damage in varying degrees in all TiO_2 NPs exposed groups.With the increase of the dose of TiO_2 NPs, the levels of ALT, AST and MDA showed increased in the 50 and 100 mg/kg·BW groups, SOD activity showed decreased in the 100 mg/kg·BW group, GSHPX activity showed decreased in the 50 and 100 mg/kg·BW groups, T-AOC level showed decreased in 10,50,100 mg/kg BW groups, the difference was statistically significant(P <0.05). Conclusion Oral exposure to TiO_2 NPs can cause liver tissue structure and function destruction, oxidative stress may be implicated in TiO_2 NPs induced liver toxicity.
Objective The research was performed to explore the effect of titanium dioxide nanoparticles(TiO_2 NPs) on liver after oral exposure to in mice. Methods 60 healthy male ICR mice were randomly divided into control group and TiO_2 NPs(10,50,100) mg/kg·BW groups. The mice were exposed to TiO_2 NPs via intragastric administration for 30 days.The liver coefficient, liver histopathology, alanine aminotransferase(ALT), aspartate aminotransferase(AST), superoxide dismutase(SOD),glutathione peroxidase(GSH-PX), total antioxidant capacity(T-AOC) activity and malondialdehyde(MDA) content were assessed after the mice were killed. Results The difference was not statistically significant of liver coefficient among TiO_2 NPs exposed groups compared with that of control group(P>0.05). Histopathological sections were observed that the liver tissue damage in varying degrees in all TiO_2 NPs exposed groups.With the increase of the dose of TiO_2 NPs, the levels of ALT, AST and MDA showed increased in the 50 and 100 mg/kg·BW groups, SOD activity showed decreased in the 100 mg/kg·BW group, GSHPX activity showed decreased in the 50 and 100 mg/kg·BW groups, T-AOC level showed decreased in 10,50,100 mg/kg BW groups, the difference was statistically significant(P <0.05). Conclusion Oral exposure to TiO_2 NPs can cause liver tissue structure and function destruction, oxidative stress may be implicated in TiO_2 NPs induced liver toxicity.
引文
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[11]王晓梅.双酚A对小鼠肝、肾氧化损伤的影响[D].衡阳:南华大学,2013:7-10.
[12]朱利娟.JNK-P38MAPK信号通路在桦木酸抑制淋巴细胞氧化损伤的分子机制[D].长沙:湖南农业大学,2017:13-14.
[13]段淑敏,张永亮,王云.纳米二氧化钛与脂多糖对小鼠肝脏抗氧化性能的影响[J].北京大学学报(医学版),2018,50(3):395-400.
[14]杨生梅.口服纳米二氧化钛的体外和体内安全性评价[D].石河子:石河子大学,2017.
[15]杨牧祥,田元祥,姚树坤,等.解酒护肝饮对酒精性肝损伤大鼠血清和肝组织ALT、AST的影响[J].河北中医,2000,(10):793-796.
[16]马虹宇,孙海鹰,孙丽芳.雌激素对雌性大鼠血清与肝组织中ALT、AST、ALP及GGT活性的影响[J].中国地方病学杂志,2000,(1):36-37.
[17]Hong J,Zhang YQ.Murine liver damage caused by exposure to nano-titanium dioxide[J].Nanotechnology,2016,27(11):112001-112015.
[18]魏凤,郭广君,吕素芳,等.细胞凋亡体外检测方法的研究进展[J].黑龙江畜牧兽医,2015,(1):58-60.
[19]刘长贵.组织病理学教学彩色图谱[M].沈阳:沈阳出版社,1999.
[20]Abdelazim SA,Darwish HA,Ali SA,et al.Potential antifibrotic and angiostatic impact of idebenone,carnosine and vitamin E in nanosized Titanium dioxide-induced liver injury[J].Cellular Physiology and Biochemistry,2015,35(6):2402-2411.
[21]Rollerova E,Tulinska J,Liskova A,et al.Titanium dioxide nanoparticles:some aspects of toxicity/focus on the development[J].Endocrine regulations,2015,49(2):97-112.
[22]郑国颖,李清钊,曹燕花,等.纳米硫化铅对大鼠肝脏的氧化损伤作用[J].中国工业医学杂志,2013,26(2):105-106.
[23]Morgan A,Ibrahim MA,Galal MK,et al.Innovative perception on using Tiron to modulate the hepatotoxicity induced by Titanium dioxide nanoparticles in male rats[J].Biomedicine and Pharmacotherapy,2018,103:553-561.
[24]毛琳,尤会会,陈绍恢,等.三氧化钨纳米方块致小鼠肝脏和肾脏的急性氧化损伤[J].环境与健康杂志,2013,30(1):9-12.
[25]Strojny B,Kurantowicz N,Sawosz E,et al.Long term influence of Carbon nanoparticles on health and liver status in rats[J].PLOS One,2015,10(12):1-18.
[2]傅伊婧,黄超,巴乾,等.食品中纳米二氧化钛的毒性效应及机制研究进展[J].中国科学(化学),2016,46(3):263-267.
[3]Geraets L,Oomen AG,Krystek P,et al.Tissue distribution and elimination after oral and intravenous administration of different Titanium dioxide nanoparticles in rats[J].Particle and Fibre Toxicology,2014,11(1):30-51.
[4]Tassinari R,Cubadda F,Moracci GA,et al.Oral,short-term exposure to Titanium dioxide nanoparticles in Sprague-Dawley rat:focus on reproductive and endocrine systems and spleen[J].Nanotoxicology,2014,8(6):654-662.
[5]王文斌,李仓廪,安丽红,等.纳米二氧化钛对大鼠氧化应激水平及海马组织结构的影响[J].环境与健康杂志,2013,30(12):1054-1057.
[6]贾芳.纳米二氧化钛对青春期小鼠睾酮生成的影响及其机制研究[D].晋中:山西农业大学,2013.
[7]Hong FS,Zhou YJ,Zhao XY,et al.Maternal exposure to nanosized Titanium dioxide suppresses embryonic development in mice[J].International Journal of Nanomedicine,2017,12:6197-6204.
[8]Canli EG,Atli G,Canli M.Response of the antioxidant enzymes of the erythrocyte and alterations in the serum biomarkers in rats following oral administration of nanoparticles[J].Environmental Toxicology and Pharmacology,2017,50:145-150.
[9]王云,陈章健,巴特,等.纳米二氧化钛对幼年和成年大鼠肝、肾组织抗氧化功能及元素含量的影响[J].北京大学学报(医学版),2014,46(3):395-399.
[10]王硕.纳米氧化石墨烯对小鼠肝脏的毒性作用[D].长春:吉林大学,2016:14-16.
[11]王晓梅.双酚A对小鼠肝、肾氧化损伤的影响[D].衡阳:南华大学,2013:7-10.
[12]朱利娟.JNK-P38MAPK信号通路在桦木酸抑制淋巴细胞氧化损伤的分子机制[D].长沙:湖南农业大学,2017:13-14.
[13]段淑敏,张永亮,王云.纳米二氧化钛与脂多糖对小鼠肝脏抗氧化性能的影响[J].北京大学学报(医学版),2018,50(3):395-400.
[14]杨生梅.口服纳米二氧化钛的体外和体内安全性评价[D].石河子:石河子大学,2017.
[15]杨牧祥,田元祥,姚树坤,等.解酒护肝饮对酒精性肝损伤大鼠血清和肝组织ALT、AST的影响[J].河北中医,2000,(10):793-796.
[16]马虹宇,孙海鹰,孙丽芳.雌激素对雌性大鼠血清与肝组织中ALT、AST、ALP及GGT活性的影响[J].中国地方病学杂志,2000,(1):36-37.
[17]Hong J,Zhang YQ.Murine liver damage caused by exposure to nano-titanium dioxide[J].Nanotechnology,2016,27(11):112001-112015.
[18]魏凤,郭广君,吕素芳,等.细胞凋亡体外检测方法的研究进展[J].黑龙江畜牧兽医,2015,(1):58-60.
[19]刘长贵.组织病理学教学彩色图谱[M].沈阳:沈阳出版社,1999.
[20]Abdelazim SA,Darwish HA,Ali SA,et al.Potential antifibrotic and angiostatic impact of idebenone,carnosine and vitamin E in nanosized Titanium dioxide-induced liver injury[J].Cellular Physiology and Biochemistry,2015,35(6):2402-2411.
[21]Rollerova E,Tulinska J,Liskova A,et al.Titanium dioxide nanoparticles:some aspects of toxicity/focus on the development[J].Endocrine regulations,2015,49(2):97-112.
[22]郑国颖,李清钊,曹燕花,等.纳米硫化铅对大鼠肝脏的氧化损伤作用[J].中国工业医学杂志,2013,26(2):105-106.
[23]Morgan A,Ibrahim MA,Galal MK,et al.Innovative perception on using Tiron to modulate the hepatotoxicity induced by Titanium dioxide nanoparticles in male rats[J].Biomedicine and Pharmacotherapy,2018,103:553-561.
[24]毛琳,尤会会,陈绍恢,等.三氧化钨纳米方块致小鼠肝脏和肾脏的急性氧化损伤[J].环境与健康杂志,2013,30(1):9-12.
[25]Strojny B,Kurantowicz N,Sawosz E,et al.Long term influence of Carbon nanoparticles on health and liver status in rats[J].PLOS One,2015,10(12):1-18.