Cellular effects of an aqueous solution of Losartan® on the survival of Escherichia coli AB1157 in the presence and absence of SnCl2, and on the physiological property (osmotic fragility) of the erytrocyte


The angiotensin receptors type 1 (AT1) have affinity by Losartan®, low affinity to non-peptides antagonists and similar effect as Angiotensin-convert-enzyme inhibitors. It have been reported that natural and synthetic products might reduce the genotoxic and cytotoxic effects related to stannous chloride (SnCl2). SnCl2 is used in nuclear medicine as a reducing agent to obtain technetium-99 m-radiopharmaceuticals. The aim of this work was to evaluate the cellular effects produced by a solution of Losartan® (25 mg/ml) on the survival of Escherichia coli AB1157 in the presence and absence of SnCl2, and on the osmotic fragility of erythrocytes of the blood of Wistar rats. Briefly, blood sample was withdrawn by Wistar rats with heparinized syringe and incubated with Losartan® solution. Saline (NaCL 0.9%) was used as a control. The samples were gently mixed with hypotonic solutions of NaCl. After that it was centrifuged and the supernadant isolated for optical determination of the hemoglobin present. E. coli AB1157 cultures (exponential growth phase) were collected by centrifugation, washed and resuspended in 0.9%NaCl. Samples were incubated in water bath shaker with: (a) SnCl2 (25 μg/ml), (b) Losartan® (25 mg/ml) and (c) SnCl2 (25 μg/ml) + Losartan® (25 mg/ml). Incubation with 0.9% NaCl was also carried out (control). At 60 min intervals, aliquots were withdrawn, diluted, spread onto Petri dishes with solid LB medium and incubated overnight. The colonies formed were counted and the survival fractions calculated. Statistical analysis was performed. The results showed that there was a significantly increase (P < 0.05) in the osmotic fragility of the blood cells treated with Losartan®. Moreover, Losartan® was also able to protect the E. coli cultures against the lesive action of SnCl2. Although, in erythrocyte the osmotic fragility was increased by the presence of Losartan® that could 1) alter the physical properties of this cell, or 2) had a direct or indirect effect on the intracellular sodium concentration or 3) had acted on the cardiovascular system. It suggested that the Losartan® did interfere strongly with cellular metabolism and did alter the survival fractions of E. coli AB1157.

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Zaidan, T. , de Matos, W. , Machado, É. , Junqueira, T. , Vicentini, S. , Presta, G. and Santos-Filho, S. (2010) Cellular effects of an aqueous solution of Losartan® on the survival of Escherichia coli AB1157 in the presence and absence of SnCl2, and on the physiological property (osmotic fragility) of the erytrocyte. Advances in Bioscience and Biotechnology, 1, 300-304. doi: 10.4236/abb.2010.14039.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Dahl?f , B., Devereux, R.B., Kjeldsen, S.E., Julius, S., Beevers, G., de Faire, U., Fyhrquist, F., Ibsen, H., Kristiansson, K., Lederballe-Pedersen, O., Lindholm, L.H., Nieminen, M.S., Omvik, P., Oparil, S. and Wedel, H. (2002) Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet, 359(9311), 995-1003.
[2] Rossi, S. (2006) Australian Medicines Handbook. Adelaide: Australian Medicines Handbook.
[3] Guo, Z.X. and Qiu, M.C. (2003) Losartan? downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat. Zhonghua Nei Ke Za Zhi, 42(6), 403-408.
[4] Habashi, J.P., Judge, D.P., Holm, T.M., Cohn, R.D., Loeys, B.L., Cooper, T.K. et al. (2006) Losartan?, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome, and preserves muscle tissue architecture in DMD mouse models. Science, 312(5770), 117- 121.
[5] Alberts, B., Johnson, A., Lewis, A., Raff, J., Roberts, M. and Walter, P. (2002) Molecular biology of the cell. Garland Science, New York.
[6] Wang, X., Wei, I., Ouyang, J.P., Muller, S., Gentils, M., Cauchois, G. and Stoltz, J.F. (2001) Effects of an angelica extract on human erythrocyte aggregation, deformation and osmotic fragility. Clinical Hemorheology and Microcirculation, 24(3), p. 201.
[7] Didelon, J., Mazeron, P., Muller, S. and Stoltz, J.F. (2000) Osmotic fragility of the erythrocyte membrane: characterization by modeling of the transmittance curve as a function of the NaCl concentration. Biorheol, 37(5-6), 409-416.
[8] Silva, C.R., Oliveira, M.B., Melo, S.F., Dantas, F.J., de Mattos, J.C., Bezerra, R.J., Caldeira-de-Araujo, A., Duatti, A. and Bernardo-Filho, M. (2002) Biological effects of stannous chloride, a substance that can produce stimulation or depression of the central nervous system. Brain Research Bulletin, 59(3), 213-216.
[9] Bernardo-Filho, M., Gutfilen, B. and Maciel, O.S. (1994) Effect of different anticoagulants on the labelling of red blood cells and plasma proteins with Tc-99m. Nuclear Medicine Communications, 15, 730-734.
[10] Dantas, F.J.S., Moraes, M.O., Mattos, J.C.P., Bezerra, R.J.A.C., Carvalho, E.F., Bernardo-Filho, M., et al. (1999) Stannous chloride mediates single strand breaks in plasmid DNA through reactive oxygen species formation. Toxicology Letters, 110(3), 129-136.
[11] Mattos, D.M.M., Gomes, M.L., Freitas, R.S., Rodrigues, P.C., Nascimento, V.D., Boasquevisque, E.M., Paula, E.F. and Bernardo-Filho, M. (2000) Assessment of the vincristine on the biodistribution of 99mTc-labelled glucoheptonic acid in female Balb/c mice. Nuclear Medicine Communications, 21, 117-121.
[12] Assis, M.L., De Mattos, J.C., Caceres, M.R., Dantas, F.J., Asad, L.M., Asad, N.R., Bezerra, R.J., Caldeira de Araujo, A. and Bernardo-Filho, M. (2002) Adaptative response to H(2)O(2) protects against SnCl (2) damage: the oxyr system involvement. Biochimie, 84(4), 291- 294.
[13] Cavalcanti, T.C., Gregorini, C.G., Guimar?es, F., Rettori, O. and Vieira-Matos, A.N. (2003) Changes in red blood cell osmotic fragility induced by total plasma and plasma fractions obtained from rats bearing progressive and regressive variants of the Walker 256 tumor. Brazilian Journal of Medical and Biological Research, 36(7), 887- 895.
[14] Ammus, S. and Yunis, A.A. (1989) Drug-induced red cell dyscrasias. Blood Review, 3(2), 71-82.
[15] Braga, A.C.S., Oliveira, M.B.N., Feliciano, G.D., Reininger, I.W., Oliveira, J.F., Silva, C.R. and Bernardo-Filho, M. (2000) Mecanismo de a??o e efeito de um derivado tiazolidin?nico na radiomarca??o de elementos sanguíneos com Tc-99m. Current Pharmaceutical Design, 6, 1179- 1191.
[16] Santos-Filho, S.D., Ribeiro, C.K., Diré, G.F., Lima, E. and Bernardo-Filho, M. (2002) Technetium, Rhenium and other Metals in Chemistry an Nuclear Medicine. In: Nicolini, M. and Mazzi, U. Eds., Padova, SGE editoriali, 6, 503-505.
[17] Nicolini, M. and Mazzi, U. (2002) Technetium, Rhenium and other Metals in Chemistry a Nuclear Medicine. Padova, SGE editoriali, 6, 503-505, 2002.
[18] Oliveira, J.F., Braga, A.C.S., ávila, A.S.R., Araújo, A.C., Cardoso, V.N., Bezerra, R.J.A.C. and Bernardo-Filho, M. Assessment of the effect of Maytenus ilicifolia (espinheira santa) extract on the labeling of red blood cells and plasma proteins with technetium-99m. Journal of Ethnopharmacology, 72(1-2), 179-184.
[19] Santos-Filho, et al. Erythrocyte osmotic fragility is the resistance of RBC hemolysis to osmotic changes that is used to evaluate RBC friability. Journal Biological Sciences, 4(3), 266-270.
[20] Wu, S.G., Jeng, F.R., Wei, S.Y., Su, C.Z. Chung, T.C., Chang, W.J.,and Chang, H.W. (1998) Red blood cell osmotic fragility in chronically hemodialyzed patients. Nephron, 78(1), 28-32
[21] Maiworm, A.I., Presta, G.A., Santos-Filho, S.D. et al. (2008) Osmotic and morphological effects on red blood cell membrane: action of an aqueous extract of Lantana camara. Revista Brasileira de Farmacognosia ou Brazilian Journal of Pharmacognosy, 18(1), 42-46.
[22] Gian, T.S., de Paoli, S., Presta, G.A. et al. (2007) Assessment of effects of a formula used in the traditional Chinese medicine (Buzhong Yi Qi Wan) on the morphologic and osmotic fragility of red. Revista Brasileira de Farmacognosia ou Brazilian Journal of Pharmacognosy, 17(4), 2007, 501-507.
[23] Howard-Flanders, P., Simsom, E. and Therlot, L. (1964) A locus that controls filament formation and sensitivity to radiation in Escherichia coli K-12. Genetics, 49(2), 237-246.
[24] De Mattos, J.C., Dantas, F.J., Bezerra, R.J.,. Bernardo-Filho, M., Cabral-Neto, J.B., Lage, C., Leit?o, A.C. and Caldeira de Araujo, A. (2000) Damage induced by stannous chloride in plasmid DNA. Toxicology Letters, 116(1-2), 159-163.
[25] Caldeira de Araujo, A. (2002) Genotoxic effects of stannous chloride (SnCl2) in K562 cell line. Food and Chemical Toxicology, 40(10), 1493-1498.
[26] Dantas, F.J., Moraes, M.O., Carvalho, E.F., Valsa, J.O., Bernardo-Filho, M. and Caldeira de Araujo, A. (1996) Lethality induced by stannous chloride on Escherichia coli AB1157: participation of reactive oxygen species. Food and Chemical Toxicology, 34(10), 959-962.
[27] Reiniger, W., Silva, C.R., Feizenszwalb, I., Mattos, J.C.P., Oliveira, F.F., Dantas, F.I.S., Bezerra, A.A.C. and Bernardo-Filho, M. (1999) Boldine action against the stannous chloride effect. Journla of Ethnopharmacology, 68(1-3), pp. 345.
[28] Melo, S.F., Soares, S.F., Costa, R.F., Silva, C.R., Oliveira, M.B.N., Bezerra, R.J.A.C. et al., (2001) Effect of the Cymbopogon citratus, Maytenus ilicifolia and Baccharis genistelloides extracts against the stannous chloride oxidative damage in Escherichia coli. Mutation Research, 496(1-2), 33-38.
[29] Bernardo-Filho, M. (2002) Effect of eggplant (Solanum melongena) extract on the in vitro labeling of blood elements with technetium-99m and on the biodistribution of sodium pertechnetate in rats. Molecular Biology of the Cell (Noisy-le- grand), 48(7), 771-776.
[30] Soares, S.F., Brito, L.C., Souza, D.E., Almeida, M.C., Bernardo, L.C. and Bernardo-Filho, M. (2004) Citotoxic effects of stannous salts and the action of Maytenus ilicifolia, Baccharis genistelloides and Cymbopogon citratus aqueous extracts. Brazilian Journal of Biomedical Engineering, 20, 2004; pp. 73-79.
[31] Tadros, T., Traber, D.L. and Herndon, D.N. (2000) Trauma and sepsis-induced hepatic ischemia and reperfusion injury: role of angiotensin II. Archives of Surgery, 135(7), 766-772.

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