Liver Aspartate Transaminase Isoenzymes as Biomarkers of Chronic Exposure to Chromium(VI)

Open access


Exposure to hexavalent chromium compounds is associated with the risk of lung cancer, dermatitis, gastrointestinal ulcers, and other tissue damages. The aim of this study was to compare liver isoenzyme and total serum activities of aspartate aminotransferase (AST) as cytotoxic biomarkers of acute and chronic cytotoxicity of CrVI. We investigated the extent of cell damage caused by chromium(VI) in acute (2.5 mg kg-1) daily doses administered over five days and chronic (0.25 mg kg-1 and 0.5 mg kg-1) daily doses administered over 15 to 60 days by measuring total AST in serum and low molecular weight AST (LMW-AST) and high molecular weight AST (HMW-AST) activities in thirty liver fractions. We also evaluated the kinetic properties and electrophoretic mobility of the LMW- and HMW-AST isoenzymes in liver subcellular fractions. Liver LMW-AST and total serum AST activities significantly decreased after 15 days of exposure (P<0.05). With continued treatment, AST activity increased by 15.67 % (P<0.05). Interestingly, changes in serum AST activity were similar to changes in the liver LMW-AST isoenzyme. Our results confirmed that total serum AST activity may serve as a reliable tissue biomarker for long-term exposures to CrVI, but they also suggest that the LMW-AST isoenzyme could be even more sensitive.

1. Mutti A, De Palma G, Goldoni M. Nuove prospettive nel monitoraggio biologico degli elementi metallici: l’esempio del cromo esavalente [New perspectives in biomonitoring of metallic elements: the example of hexavalent chromium, in Italian]. G Ital Med Lav Ergon 2012;34:51-4. PMID: 23213798

2. Scarselli A, Binazzi A, Marzio DD, Marinaccio A, Iavicoli S. Hexavalent chromium compounds in the workplace: assessing the extent and magnitude of occupational exposure in Italy. J Occup Environ Hyg 2012;9:398-407. doi: 10.10 80/15459624.2012.682216

3. Myers JM, Antholine WE, Myers CR. Hexavalent chromium causes the oxidation of thioredoxin in human bronchial epithelial cells. Toxicology 2008;246:222-33. doi: 10.1016/ j.tox.2008.01.017

4. Nickens KP, Patierno SR, Ceryak S. Chromium genotoxicity: A double-edged sword. Chem Biol Interact 2010;188:276-88. doi: 10.1016/j.cbi.2010.04.018

5. Yoshida M, Hatakeyama E, Hosomi R, Kanda S, Nishiyama T, Fukunaga K. Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate. J Toxicol Sci 2010;35:485-91. PMID: 20686335

6. Zhitkovich A, Quievryn G, Messer J, Motylevich Z. Reductive activation with cysteine represents a chromium(III)- dependent pathway in the induction of genotoxicity by carcinogenic chromium(VI). Environ Health Perspect 2002;110(Suppl 5):729-31. PMID: 12426121

7. Wise SS, Holmes AL, Wise JP Sr. Hexavalent chromiuminduced DNA damage and repair mechanisms. Rev Environ Health 2008;23:39-57. doi: 10.1515/REVEH.2008.23.1.39

8. Patlolla AK, Barnes C, Yedjou C, Velma VR, Tchounwou PB. Oxidative stress, DNA damage, and antioxidant enzyme activity induced by hexavalent chromium in Sprague-Dawley rats. Environ Toxicol 2009;24:66-73. doi: 10.1002/ tox.20395

9. Thompson CM, Fedorov Y, Brown DD, Suh M, Proctor DM, Kuriakose L, Haws LC, Harris MA. Assessment of CrVIinduced cytotoxicity and genotoxicity using high content analysis. PLoS One 2012;7:e42720. doi: 10.1371/journal. pone.0042720

10. Costa AN, Moreno V, Prieto MJ, Urbano AM, Alpoim MC. Induction of morphological changes in BEAS-2B human bronchial epithelial cells following chronic sub-cytotoxic and mildly cytotoxic hexavalent chromium exposures. Mol Carcinog 2010;49:582-91. doi: 10.1002/mc.20624

11. Ernst E, Bonde JP. Sex hormones and epididymal sperm parameters in rats following sub-chronic treatment with hexavalent chromium. Human Exp. Toxicol. 1992; 11:255-258. PIMD: 1354972

12. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63. PMID: 13458125

13. Karmen A, Wroblewski F, Ladue JS. Transaminase activity in human blood. J Clin Invest 1955;34:126-31. doi: 10.1172/ JCI103055

14. Lowry OH, Rosebrough MJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75. PMID: 14907713

15. Liu W, Chaspoul F, Botta C, De Meo M, Gallice P. Bioenergetics and DNA alteration of normal human fibroblasts by hexavalent chromium. Environ Toxicol Pharmacol 2010;29:58-63. doi: 10.1016/j.etap.2009.10.001

16. Myers CR, Antholine WE, Myers JM. The pro-oxidant chromium(VI) inhibits mitochondrial complex I, complex II, and aconitase in the bronchial epithelium: EPR markers for Fe-S proteins. Free Radic Biol Med 2010;49:1903-15. doi: 10.1016/j.freeradbiomed.2010.09.020

17. Bagchi D, Stohs SJ, Downs BW, Bagchi M, Preuss HG. Cytotoxicity and oxidative mechanisms of different forms of chromium. Toxicology 2002;180:5-22. doi: 10.1016/ S0300-483X(02)00378-5

18. Mohan S, Kapoor A, Singgihi A, Zhang Z, Taylor T, Yu H, Chadwick RB, Chung YS, Donahue Lr, Rosen C, Crawford GC, Wergedal J, Baylink Dj. Spontaneous fractures in the mouse mutant sfx are caused by deletion of the gulonolactone oxidase gene, causing vitamin C defi ciency. J Bone Miner Res 2005;20:1597-610. doi: 10.1359/JBMR.050406

19. Hemmati AA, Nazari Z, Ranjbari N, Torfi A. Comparison of the preventive effect of vitamin C and E on hexavalent chromium induced pulmonary fibrosis in rat. Inflammopharmacology 2008;16:195-7. doi: 10.1007/ s10787-008-7004-4

20. Wang XF, Lou XM, Shen Y, Xing mL, Xu LH. Apoptoticrelated protein changes induced by hexavalent chromium in mice liver. Environ Toxicol 2010;25:77-82. doi: 10.1002/ tox.20478

21. Bour-Jr W, Hamm-Ming S, Yue-Liang G, Yu-Hsuan L, Ching- Shu L, Min-Hsiung P, Ying-Jan W. Hexavalent chromium induced ROS formation, Akt, NF-kappaB, and MAPK activation, and TNF-α and IL-1α production in keratinocytes. Toxicol Lett 2010;198:216-24. doi: 10.1016/ j.toxlet.2010.06.024

22. Samuel JB, Stanley JA, Roopha DP, Vengatesh G, Anbalagan J, Banu SK, Aruldhas MM. Lactational hexavalent chromium exposure-induced oxidative stress in rat uterus is associated with delayed puberty and impaired gonadotropin levels. Hum Exp Toxicol 2001;30:91-101. doi: 10.1177/0960327110364638

23. Tajima H, Yoshida T, Ohnuma A, Fukuyama T, Hayashi K, Yamaguchi S, Ohtsuka R, Sasaki J, Tomita M, Kojima S, Takahashi N, Kashimoto Y, Kuwahara M, Takeda M, Kosaka T, Nakashima N, Harada T. Pulmonary injury and antioxidant response in mice exposed to arsenate and hexavalent chromium and their combination. Toxicology 2010;267:118-24. doi: 10.1016/j.tox.2009.10.032

24. Krumschnabel G, Nawaz M. Acute toxicity of hexavalent chromium in isolated teleost hepatocytes. Aquat Toxicol 2004;70:159-67. doi: 10.1016/j.aquatox.2004.09.001

25. Griselda RB, William EA, Kalyanaraman B, Judith MM, Charles RM. Reduction of hexavalent chromium by human cytochrome b5: generation of hydroxyl radical and superoxide. Free Radic Biol Med 2007;42:738-55. doi: 10.1016/j. freeradbiomed.2006.10.055

26. O,Brien TJ, Ceryak S, Patierno SR. Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat Res 2003;533:3-36. doi: 10.1016/j.mrfmmm.2003.09.006

Archives of Industrial Hygiene and Toxicology

The Journal of Institute for Medical Research and Occupational Health

Journal Information

IMPACT FACTOR 2017: 1.117
5-year IMPACT FACTOR: 1.335

CiteScore 2017: 1.24

SCImago Journal Rank (SJR) 2017: 0.341
Source Normalized Impact per Paper (SNIP) 2017: 0.494


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 289 287 33
PDF Downloads 106 105 11