Abstract
Nitrite and nitrite are considered hazardous, and there are legal limits to their concentration in food and drinking water. The typical diet in most countries contains nitrites, nitrites, and nitrosamines. It is used as a food preservative, especially in cured meats. In this research, we investigated the cytotoxic mechanisms of sodium nitrite in isolated hepatocyte. For this purpose, we evaluated the several oxidative stress markers. The results showed that the cytotoxicity of sodium nitrite on hepatocytes was associated with reactive oxygen species (ROS) formation and lipid peroxidation which were inhibited by antioxidants and ROS scavengers, mitochondrial permeability transition, pore sealing agents and endocytosis inhibitors. Sodium nitrite cytotoxicity was also associated with mitochondrial injury, lysosomal membrane rupture and release of digestive proteases which were prevented by antioxidants, mitochondrial permeability transition (MPT) pore sealing agents and lysosomotropic agents. In conclusion, sodium nitrite at concentration of 5 mM could have cytotoxic effects on isolated rat hepatocytes by above mentioned mechanisms.
Similar content being viewed by others
References
Bradbury, K. E., Appleby, P. N. & Key, T. J. Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Am. J. Clin. Nutr. 100 Suppl 1, 394S–398S (2014).
Gonzalez, C. A. et al. Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up. Int. J. Cancer. 131, 2910–2919 (2012).
Ward, M. H., Heineman, E. F., McComb, R. D. & Weisenburger, D. D. Drinking water and dietary sources of nitrate and nitrite and risk of glioma. J. Occup. Environ. Med. 47, 1260–1267 (2005).
Li, Z. W., Ren, A. G., Guan, L. X. & Li, Z. [Nitrate and nitrite contents of drinking water in some areas of Shanxi Province]. Wei. Sheng. Yan. Jiu. 35, 217–218 (2006).
Sungur, S. & Atan, M. M. Determination of nitrate, nitrite and perchlorate anions in meat, milk and their products consumed in Hatay region in Turkey. Food. Addit. Contam. Part B. Surveill. 6, 6–10 (2013).
Yalcin, S. & Yalcin, S. S. Nitrate and nitrite content of meat products. Arch. Dis. Child. 79, 198 (1998).
Gotterup, J. et al. Relationship between nitrate/nitrite reductase activities in meat associated staphylococci and nitrosylmyoglobin formation in a cured meat model system. Int. J. Food. Microbiol. 120, 303–310 (2007).
Budayova, E. Effects of sodium nitrite and potassium sorbate on in vitro cultured mammalian cells. Neoplasma 32, 341–350 (1985).
Sun, J., Aoki, K., Wang, W., Guo, A. & Misumi, J. Sodium nitrite-induced cytotoxicity in cultured human gastric epithelial cells. Toxicol. In Vitro. 20, 1133–1138 (2006).
Wary, K. K. & Sharan, R. N. Cytotoxic and cytostatic effects of arecoline and sodium nitrite on human cells in vitro. Int. J. Cancer. 47, 396–400 (1991).
Pourahmad, J. et al. A new approach on valproic acid induced hepatotoxicity: involvement of lysosomal membrane leakiness and cellular proteolysis. Toxicol. In Vitro. 26, 545–551 (2012).
Pourahmad, J., Mortada, Y., Eskandari, M. R. & Shahraki, J. Involvement of Lysosomal Labilisation and Lysosomal/mitochondrial Cross-Talk in Diclofenac Induced Hepatotoxicity. Iran. J. Pharm. Res. 10, 877–887 (2011).
Craddock, V. M. Nitrosamines, food and cancer: assessment in Lyon. Food. Chem. Toxicol. 28, 63–65 (1990).
Griesenbeck, J. S. et al. Development of estimates of dietary nitrates, nitrites, and nitrosamines for use with the short willet food frequency questionnaire. Nutr. J. 8, 16 (2009).
Hsu, J., Arcot, J. & Lee, N. A. Nitrate and nitrite quantification from cured meat and vegetables and their estimated dietary intake in Australians. Food. Chem. 115, 334–339 (2009).
Machha, A. & Schechter, A. N. Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits. Eur. J. Nutr. 50, 293–303 (2011).
Varraso, R., Jiang, R., Barr, R. G., Willett, W. C. & Camargo, C. A., Jr. Prospective study of cured meats consumption and risk of chronic obstructive pulmonary disease in men. Am. J. Epidemiol. 166, 1438–1445 (2007).
Jiang, R. et al. Consumption of cured meats and prospective risk of chronic obstructive pulmonary disease in women. Am. J. Clin. Nutr. 87, 1002–1008 (2008).
Pourahmad, J., Eskandari, M. R. & Daraei, B. A comparison of hepatocyte cytotoxic mechanisms for Thallium (I) and Thallium (III). Environ. Toxicol. 25, 456–467 (2010).
Pourahmad, J., Rabiei, M., Jokar, F. & O’Brien, P. J. A comparison of hepatocyte cytotoxic mechanisms for chromate and arsenite. Toxicology 206, 449–460 (2005).
Pourahmad, J., Eskandari, M. R., Shakibaei, R. & Kamalinejad, M. A search for hepatoprotective activity of fruit extract of Mangifera indica L. against oxidative stress cytotoxicity. Plant. Foods. Hum. Nutr. 65, 83–89 (2010).
Hosseini, M.-J., Shaki, F., Ghazi-Khansari, M. & Pourahmad, J. Toxicity of Copper on Isolated Liver Mitochondria: Impairment at Complexes I, II, and IV Leads to Increased ROS Production. Cell Biochem. Biophys. 70, 367–381 (2014).
Church, F. C., Swaisgood, H. E., Porter, D. H. & Catignani, G. L. Spectrophotometric Assay Using Ortho-Phthaldialdehyde for Determination of Proteolysis in Milk and Isolated Milk-Proteins. J. Dairy. Sci. 66, 1219–1227 (1983).
Juffs, H. S. Proteolysis detection in milk. I. Interpretation of tyrosine value data for raw milk supplies in relation to natural variation, bacterial counts and other factors. J. Dairy. Res. 40, 371–381 (1973).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Kiani, A., Yousefsani, B.S., Doroudian, P. et al. The mechanism of hepatotoxic effects of sodium nitrite on isolated rat hepatocytes. Toxicol. Environ. Health Sci. 9, 244–250 (2017). https://doi.org/10.1007/s13530-017-0327-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13530-017-0327-z