Ukr.Biochem.J. 2020; Volume 92, Issue 4, Jul-Aug, pp. 45-54
doi: https://doi.org/10.15407/ubj92.04.045
ТiО(2) hepatotoxicity under long-term administration to rats
O. V. Tsymbalyuk, S. P. Veselsky, A. M. Naumenko, T. L. Davydovska,
I. S. Voiteshenko, I. I. Сhyzh, V. A. Skryshevsky
Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: otsymbal@bigmir.net
Received: 30 March 2020; Accepted: 15 May 2020
Titanium dioxide (ТіО2) powder which is used as a white dye was considered to be an inert material for a long time despite its accumulation in liver tissues after penetration into organism. The aim of the study was to estimate biochemical markers of liver functioning in blood plasma and ATPase activity of erythrocyte plasma membrane under the oral administration of ТіО2 nanoparticles suspension (0.1 mg/kg, daily) to Wistar rats for 30 and 100 days. A significant increase of alanine aminotransferase and aspartate aminotransferase activity as well as of direct, indirect and bound bilirubin content, a decrease of connjugated (taurocholic, taurochenodeoxycholic, taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic) and free (glycodeoxycholic and deoxycholic) bile acids concentration with concomitant increase of free cholic acid concentration in blood plasma of rats under ТіО2 administration were revealed, indicating a significant impairment of pigment exchange in the liver of rats. Under ТіО2 administration a substantial inhibition of erythrocyte plasma membrane Мg2+-dependent ouabain-sensitive Na+,K+-ATPase and ouabain-insensitive ATPase was observed. These results presume the disturbance of transplasmalema ion-transporting processes and cells ionic homeostasis induced by ТіО2.
Keywords: alanine aminotransferase, aspartate aminotransferase, bile acids, bilirubin, plasma membrane ATPase activities, TiO2 nanoparticles
References:
- Song Y, Chen S. Janus nanoparticles: preparation, characterization, and applications. Chem Asian J. 2014;9(2):418-430. PubMed, CrossRef
- Trovato MC, Andronico D, Sciacchitano S, Ruggeri RM, Picerno I, Di Pietro A, Visalli G. Nanostructures: between natural environment and medical practice. Rev Environ Health. 2018;33(3):305-317. PubMed, CrossRef
- Proquin H, Jetten MJ, Jonkhout MCM, Garduño-Balderas LG, Briedé JJ, de Kok TM, van Loveren H, Chirino YI. Transcriptomics analysis reveals new insights in E171-induced molecular alterations in a mouse model of colon cancer. Sci Rep. 2018;8(1):9738. PubMed, PubMedCentral, CrossRef
- Xu F. Review of analytical studies on TiO2 nanoparticles and particle aggregation, coagulation, flocculation, sedimentation, stabilization. Chemosphere. 2018;212:662-677. PubMed, CrossRef
- Weir A, Westerhoff P, Fabricius L, Hristovski K, von Goetz N. Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol. 2012;46(4):2242-2250. PubMed, PubMedCentral, CrossRef
- De Matteis V, Cascione M, Brunetti V, Toma CC, Rinaldi R. Toxicity assessment of anatase and rutile titanium dioxide nanoparticles: The role of degradation in different pH conditions and light exposure. Toxicol In Vitro. 2016;37:201-210. PubMed, CrossRef
- Bettini S, Boutet-Robinet E, Cartier C, Coméra C, Gaultier E, Dupuy J, Naud N, Taché S, Grysan P, Reguer S, Thieriet N, Réfrégiers M, Thiaudière D, Cravedi JP, Carrière M, Audinot JN, Pierre FH, Guzylack-Piriou L, Houdeau E. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon. Sci Rep. 2017;7:40373. PubMed, PubMedCentral, CrossRef
- Tsymbalyuk OV, Naumenko AM, Rohovtsov OO, Skoryk MA, Voiteshenko IS, Skryshevsky VA, Davydovska TL. Titanium Dioxide Modulation of the Contractibility of Visceral Smooth Muscles In Vivo. Nanoscale Res Lett. 2017;12(1):129. PubMed, PubMedCentral, CrossRef
- Tsymbalyuk OV, Naumenko AM, Skoryk MA, Nyporko AY, Davidovska TL, Skryshevsky VA. Histamine- and nicotine-stimulated modulations of mechanic activity of smooth muscles in gastrointestinal tract at the impact of nanosized TiO2 material. Biopolym Cell. 2016;32(2):140-149. CrossRef
- Naumenko AM, Dmytrenko OV, Shapoval LM, Tsymbalyuk OV, Sagach VF, Davydovska TL. Effects of Injections of Nanostructured Titanium Dioxide into the Rat Medullary Nuclei Involved in Cardiovascular Control. Neurophysiology. 2018; 50(6): 409-414. CrossRef
- Khalili Fard J, Jafari S, Eghbal MA. A Review of Molecular Mechanisms Involved in Toxicity of Nanoparticles. Adv Pharm Bull. 2015;5(4):447-454.
PubMed, PubMedCentral, CrossRef - Adverse Effects of Engineered Nanomaterials: Exposure, Toxicology, and impact on human health. Second Edition / Edited by Fadeel B., Pietroiusti A., Shvedova A.A., Elsevier, Academic Press, 2017, 468 p.
- Geraets L, Oomen AG, Krystek P, Jacobsen NR, Wallin H, Laurentie M, Verharen HW, Brandon EFA, de Jong WH. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats. Part Fibre Toxicol. 2014; 11:30. PubMed, PubMedCentral, CrossRef
- Abbasi-Oshaghi E, Mirzaei F, Pourjafar M. NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study. Int J Nanomedicine. 2019;14:1919-1936. PubMed, PubMedCentral, CrossRef
- Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957;28(1): 56-63. PubMed, CrossRef
- Jendrassik L, Grof P. Colorimetric Method of Determination of bilirubin. Biochem Z. 1938;297:81-82.
- Cohen PP, Thompson FL. Mechanism of the thymol turbidity test. J Lab Clin Med. 1947;32(5):475-480. PubMed
- A. c. № 441106614 USSR MTIS 01W33 / 50 Veselsky S.P., Lyashchenko P.S., Lukyanenko I.A. A method for determining bile acids in biological fluids. USSR No. 1624322 declared 25.01.1988, published 30.01.1991, bull. № 4 (In Russian)
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1): 265-275. PubMed
- Tsymbalyuk OV, Kosterin SO, Rodik RV, Kalchenko VI. Comparative study in vitro and in vivo of the effects of calixarene C107 and oubaine on Na+, K+-ATPase activity in the plasma membranes of rat hepatocytes. Ukr Biokhim Zhurn. 2010;82(4):78-85. (In Ukrainian). PubMed
- Rathbun WB, Betlach MV. Estimation of enzymatically produced orthophosphate in the presence of cysteine and adenosine triphosphate. Anal Biochem. 1969; 28(1): 436-445. PubMed, CrossRef
- Hong J, Zhang Yu-Q. Murine liver damage caused by exposure to nano-titanium dioxide. Nanotechnology. 2016;27(11):112001. PubMed, CrossRef
- Hofmann AF, Hagey LR. Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology and Therapeutics. Cell Mol Life Sci. 2008;65(16): 2461-2483. PubMed, CrossRef
- Hoffmann WE, Solter PhF. in Clinical Biochemistry of Domestic Animals (Sixth Edition), Chapter 12 – Diagnostic Enzymology of Domestic Animals / Academic Press, 2008, P. 351-378.
CrossRef - De Ritis F, Giusti G, Piccinino F, Cacciatore L. Biochemical laboratory tests in viral hepatitis and other hepatic diseases. Evaluation and follow-up. Bull World Health Organ. 1965;32(1):59-72. PubMed, PubMedCentral
- Botros M, Sikaris KA. The de Ritis ratio: the test of time. Clin Biochem Rev. 2013;34(3):117-130. PubMed, PubMedCentral
- Tsymbaliuk OV, Kosterin SO. Na+,K+-ATPase, endogenous cardiotonic steroids and their transducing role. Ukr Biokhim Zhurn. 2012;84(1):5-17. (In Ukrainian). PubMed
- Yang J, Luo M, Tan Z, Dai M, Xie M, Lin J, Hua H, Ma Q, Zhao J, Liu A. Oral administration of nano-titanium dioxide particle disrupts hepatic metabolic functions in a mouse model. Environ Toxicol Pharmacol. 2017;49:112-118. PubMed, CrossRef
- Kreyling WG, Holzwarth U, Schleh C, Kozempel J, Wenk A, Haberl N, Hirn S, Schäffler M, Lipka J, Semmler-Behnke M, Gibson N. Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats: Part 2. Nanotoxicology. 2017;11(4):443-453. PubMed, CrossRef
- Hong F, Yu X, Wu N, Zhang YQ. Progress of in vivo studies on the systemic toxicities induced by titanium dioxide nanoparticles. Toxicol Res. (Camb). 2017;6(2):115-133. PubMed, PubMedCentral, CrossRef
- Mohammadpour R, Dobrovolskaia MA, Cheney DL, Greish KF, Ghandehari H. Subchronic and chronic toxicity evaluation of inorganic nanoparticles for delivery applications. Adv Drug Deliv Rev. 2019;144:112-132. PubMed, PubMedCentral, CrossRef
- Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol. 2013;10:15. PubMed, PubMedCentral, CrossRef
- Shakeel M, Jabeen F, Qureshi NA, Fakhr-E-Alam M. Toxic Effects of Titanium Dioxide Nanoparticles and Titanium Dioxide Bulk Salt in the Liver and Blood of Male Sprague-Dawley Rats Assessed by Different Assays. Biol Trace Elem Res. 2016;173(2):405-426. PubMed, CrossRef
- Jia X, Wang S, Zhou L, Sun L. The Potential Liver, Brain, and Embryo Toxicity of Titanium Dioxide Nanoparticles on Mice. Nanoscale Res Lett. 2017;12(1):478. PubMed, PubMedCentral, CrossRef
- Słomka M, Szczerbo-Trojanowska M, Celiński K, Skrzydło-Radomańska B. [Evaluation of the consequences of hepatic artery embolization under experimental conditions. Ann Univ Mariae Curie Sklodowska Med. 1991;46:81-87. (In Polish). PubMed
- Li Y, Yan J, Ding W, Chen Y, Pack LM, Chen T. Genotoxicity and gene expression analyses of liver and lung tissues of mice treated with titanium dioxide nanoparticles. Mutagenesis. 2017;32(1):33-46. PubMed, CrossRef
- Chen T, Yan J, Li Y. Genotoxicity of titanium dioxide nanoparticles. J Food Drug Anal. 2014;22(1):95-104. PubMed, PubMedCentral, CrossRef
- Shalan H, Kato M, Cheruzel L. Keeping the spotlight on cytochrome P450. Biochim Biophys Acta Proteins Proteom. 2018;1866(1):80-87. PubMed, PubMedCentral, CrossRef
- Natarajan V, Wilson CL, Hayward SL, Kidambi S. Titanium Dioxide Nanoparticles Trigger Loss of Function and Perturbation of Mitochondrial Dynamics in Primary Hepatocytes. PLoS One. 2015;10(8):e0134541. PubMed, PubMedCentral, CrossRef
- Hong F, Si W, Zhao X, Wang L, Zhou Y, Chen M, Ge Y, Zhang Q, Wang Y, Zhang J. TiO2 Nanoparticle Exposure Decreases Spermatogenesis via Biochemical Dysfunctions in the Testis of Male Mice. J Agric Food Chem. 2015;63(31):7084-7092. PubMed, CrossRef
- Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, Zhou M, Liu C, Wang H, Hong F. Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles. Biomaterials. 2010;31(31):8043-8050. PubMed, CrossRef
- Yu X, Hong F, Zhang YQ. Cardiac inflammation involving in PKCε or ERK1/2-activated NF-κB signalling pathway in mice following exposure to titanium dioxide nanoparticles. J Hazard Mater. 2016;313:68-77. PubMed, CrossRef
- Garduño-Siciliano L, Labarrios F, Tamariz J, Moreno MG, Chamorro G, Muriel P. Effect of alpha-asarone and a derivative on lipids, bile flow and Na+/K+-ATPase in ethinyl estradiol-induced cholestasis in the rat. Fundam Clin Pharmacol. 2007;21(1):81-88. PubMed, CrossRef
