Cypermethrin, deltamethrin and glyphosate affect the activity of the Ca2 +-ATPase from human erythrocyte

Cipermetrina, deltametrina y glifosato afectan la actividad enzimática de la Ca2+-ATPasa de eritrocito humano

  • Javier Vargas-Medrano Texas Tech University Health Science Center and Paul L. Foster School of Medicine. El Paso, TX, U.S.A.
  • Jorge A. Sierra-Fonseca University of Texas at El Paso, El Paso, TX, U.S.A.
  • Manuel Arellano-Carrillo Universidad Autónoma de Ciudad Juárez
  • Fernando Plenge-Tellechea Universidad Autónoma de Ciudad Juárez
Palabras clave: PMCA (plasma membrane Ca2 -ATPase), SERCA (sarco/endoplasmic Ca2 -ATPase) enzymatic activity, cypermethrin, deltamethrin, glyphosate



The extensive use of pesticides can cause many human health problems. However, the effects of pesticides on a biochemical level are still poorly understood. In this study we analyzed the effect of different pesticides on the plasma membrane Ca2+-ATPase (PMCA) and on the sarco/ endoplasmic reticulum Ca2+-ATPase (SERCA) activities. Different amounts of pesticides were added to the Ca2+- dependent ATPase assays in order to determine if they were affecting the ATPase activity. The results showed that PMCA activity was partially inhibited by deltamethrin to 51.85% ± 3.7 when its concentration in the reaction medium was 0.5 mM, while cypermethrin and glyphosate stimulated the PMCA activity at the lowest concentrations tested. The maximum stimulatory effect of cypermethrin was of 155% ± 9.0 at a concentration of 0.2 mM. In addition, the herbicide glyphosate stimulated the activity 111% ± 2.0 at a concentration of 0.2 mM. In conclusion, our results showed that PMCA activity was partially inhibited by deltamethrin, but cypermethrin and glyphosate stimulated their activity. Our findings suggest that cypermethrin and deltamethrin have different structure- activity relationships. However, SERCA was not sensitive to deltamethrin or glyphosate. These differences may be reflected in disturbs over cellular calcium regulation.


Se ha observado que la exposición de personas a plaguicidas puede causar problemas a la salud. Sin embargo, el estudio del efecto de plaguicidas a un nivel bioquímico ha sido pobremente estudiado. En este estudio, analizamos el efecto de cipermetrina, deltametrina y glifosato sobre la actividad enzimática de las Ca2+- ATPasa de membrana plasmática (PMCA) y de retículo sarcoplásmico (SERCA). Diferentes concentraciones de estos pesticidas fueron añadidas a los experimentos de actividad enzimática como estrategia para determinar si estos compuestos eran capaces de afectar la actividad enzimática de PMCA. Nuestros resultados demuestran que la actividad enzimática de PMCA fue parcialmente inhibida por deltametrina en un 51.85% ± 3.7 cuando su concentración fue de 0.5 mM, mientras que cipermetrina y glifosato estimularon la actividad enzimática de PMCA a menores concentraciones. El máximo efecto estimulatorio de cipermetrina fue de 155% ± 9.0 cuando el compuesto alcanzó una concentración de 0.2 mM. Además, el herbicida glifosato fue capaz de estimular la actividad enzimática de PMCA en un 111% ± 2.0 a concentraciones de 0.1-0.2 mM. En conclusión, nuestros resultados demostraron que la actividad enzimática de PMCA fue también parcialmente inhibida con deltametrina, pero al contrario de cipermetrina y glifosato la estimularon. Nuestros resultados sugieren que las diferencias en las estructuras químicas de cipermetrina y deltametrina se ven reflejadas en el efecto provocado sobre PMCA. Sin embargo, una enzima similar, SERCA, no fue afectada ni por deltametrina ni glifosato. Estas diferencias se pudieran ver reflejadas en disturbios sobre la regulación celular del calcio.

Palabras clave: PMCA (ATPasa de Ca2+ de membrana plasmática), SERCA (ATPasa de Ca2+ de retículo endo/sarcoplásmico), actividad enzimática, cipermetrina, deltametrina, glifosato.


Ahsan, N., D.G. Lee, K.W. Lee, I. Alam, S.H. Lee, J.D. Bahkm & B.H. Lee. 2008. Glyphosate-induced oxidative stress in rice leaves revealed by proteomic approach. Plant Physiology and Biochemistry 46(12):1062-70.

Alavanja, M.C.R., J.A. Hoppin & F. Kamel. 2004. Health effect of chronic pesticide exposure: cancer and neurotoxicity. Annual Review of Public Health 25:155-197.

Antunes-Madeira, M.C., R.A. Videira & V.M. Madeira. 1994. Effects of parathion on membrane organization and its implications for the mechanisms of toxicity. Biochimica et Biophysica Acta 1190(1):149-154.

Baykov, A.A., O.A. Evdushenko & S.M. Avaeva. 1988. A malachite green procedure for orthophosphate determination and its use in alkaline phosphatase-based enzyme immunoassay. Analytical Biochemistry 171(2):266-270.

Benaim, G., V. Cervino, C. Lopez-Estraño & C. Weitzman. 1994. Ethanol stimulates the plasma membrane calcium pump from human erythrocytes. Biochimica et Biophysica Acta 1195(1): 141-148.

Berlin, J.R., T. Akera, T.M. Brody & F. Matsumura.1984. The inotropic effects of a synthetic pyrethroid on isolated guinea pig atrial muscle. European Journal of Pharmacology 98(3-4):313-322.

Bhalla, P. & D. Agrawal. 1998. Alterations in rat erythrocyte membrane due to hexachlorocyclohexane (technical) exposure. Human & Experimental Toxicology 17(11):638-642.

Blasiak, J. 1995. Cooperative binding of the organophosphate paraoxon to the (Na++K+)-ATPase. Int. Immunopharmacol. 5(2):263-270.

Blinks, J. R., W. G. Wier, P. Hess & F. G. Prendergast. 1982. Measurement of Ca2+ concentrations in living cells. Progress in Biophysics and Molecular Biology 51(6):475-480.

Carafoli, E. 1992. The Ca2+ pump of the plasma membrane. Journal of Biological Chemistry 267(4):2115-2118.

Carafoli, E. 2002. Calcium signaling: a tale for all seasons. Proceedings of the National Academy of Sciences of the United States of America 99(3):1115-1122.

Chefurka, W., R. C. Chatelier & W.H Sawyer. 1987. Perturbation of phospholipid bilayers by DDT. Biochimica et Biophysica Acta 896(2):181- 186.

Clark, J.M. & F. Matsumura. 1987. The action of two classes of pyrethroids on the inhibition of brain Na-Ca and Ca+Mg ATP hydrolyzing activities of the American cockroach. Comparative Biochemistry and Physiology Part C: Comparative Pharmacology 86(1):135-145.

Corasaniti, M.T., G. Bagetta, P. Rodinò,S. Gratteri & G. Nisticò. 1992. Neurotoxic effects induced by intracerebral and systemic injection of paraquat in rats. Human & Experimental Toxicology 11(6): 535-539.

Courtney, K.D. 1979. Hexachlorobenzene (HCB): a review. Environmental Research 20(2):225-266.

Cremer, J.E. 1983. The influence in mammals of the pyrethroid insecticides. Developments in Toxicology Sciences and Environmental Toxicology 11:61-72.

Deamer, D.W. & R.J. Baskin. 1969. Ultrastructure of sarcoplasmic reticulum preparations. Journal of Cellular Biology 42(1):296-307.

Deroosa, A.J., A. Blair, J.A. Rusiecki, J.A. Hoppin, M. Svec, M. Dosemeci, D.P. Sandler & M.C. Alavanja. 2005. Cancer incidence among Glyphosate-exposed pesticide applicators in the agricultural health study. Environmental Health Perspectives 113(1):49-54.

Diel, F., B. Horr, H. Borck & T. Irman-Florjanc. 2003. Pyrethroid insecticides influence the signal transduction in T helper lymphocytes from atopic and nonatopic subjects. Inflammation Research 52(4):154-163.

Duchnowicz, P. & M. Koter. 2003. Damage to erythrocyte membrane caused by chlorophenoxyacetic herbicides. Cellular & Molecular Biology Letters 8(1):25-30.

Eletr, S. & G. Inesi. 1972. Phospholipid orientation in sarcoplasmic membranes: spin-label ESR and proton MNR studies. Biochimica et Biophysica Acta (BBA)-Biomembranes 282(1):174-179.

Fabiato, A. & F. Fabiato. 1979. Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. Journal de Physiologie 75(5):463-505.

Giray, B., A. Gürbay & F. Hincal. 2001. Cypermethrin-induced oxidative stress in rat brain and liver is prevented by vitamin E or allopurinol. Toxicology Letters 118(3):139-46.

Gottfriedg, E.L. 1967. Lipids of human leukocytes: relation to cell type. Journal of Lipid Research 8(4): 321-327.

Grosman, N. & F. Diel. 2005. Influence of pyrethroids and piperonylbutoxide on the Ca2+-ATPase activity of rat brain synaptosomes and leukocyte membranes. International Immunopharmacology 5(2):263-270.

Hazarika, A., S.N. Sarkar & M. Kataria. 2001. Subacute toxicity of anilofos, a new organophosphate herbicide in male rats: effect on lipid peroxidation and ATPase activity. Indian Journal of Experimental Biology 39(11):1113-1117.

Janik, F. & H.U. Wolf. 1992.The Ca (2+)-transport-ATPase of human erythrocytes as an in vitro toxicity test system—acute effects of some chlorinated compounds. Journal of Applied Toxicology 12(5):351-358.

Jones, O.T., R.J. Froud & A.G. Lee. 1985. Interactions of hexachlorocyclohexanes with the (Ca2+ + Mg2+)-ATPase from sarcoplasmic reticulum. Biochimica et Biophysica Acta (BBA)-Biomembranes 812(3):740-751.

Kakko, I., T. Toimela & H. Tähti. 2003. The synaptosomal membrane bound ATPase as a target for the neurotoxic effects of pyrethroids, permethrin and cypermethrin. Chemosphere 51(6):475-480.

Khan, S.Z., C.L. Longland & F. Michelangeli. 2000. The effects of phenothiazines and other calmodulin antagonists on the sarcoplasmic and endoplasmic reticulum Ca2+ pumps. Biochemical Pharmacology 60(12):1797-1806.

Knauf, P.A., F. Provervio & J.F. Hoffmann. 1974. Electrophoretic separation of different phosphoproteins associated with Ca2+- ATPase and Na+, K+-ATPase in human red cell ghosts. Journal of General Physiology 63(3):324-336.

Kodavanti, P. R. S., W.R. Mundy, H.A. Tilson & G. J. Harry. 1993. Effects of selected neuroactive chemicals on calcium transporting systems in rat cerebellum and on survival of cerebellar granule cells. Fundamental and Applied Toxicology 21(3):308-16.

Lam, M., G. Dubyak, L. Chen, G. Nuñez, R.L. Miesfeld & C.W. Distelhorst. 1994. Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+ fluxes. Proceedings of the National Academy of Sciences 91(14):6569-6573.

Lanzetta, P.A., L.J. Alvarez, P.S. Reinach & O.A. Candia. 1979. An improved assay for nanomole amounts of inorganic phosphate. Analytical Biochemistry 100(1):95-97.

Lax, A., F. Soler & F. Fernandez-Belda. 2002. Inhibition of 2+ sarcoplasmic reticulum Ca -ATPase by miconazole. American Journal of Physiology Cell Physiology 283(1):C85-92.

Lee, A.G. 1998. How lipids interact with an intrinsic membrane protein: the case of the calcium pump. Biochimica et Biophysica Acta (BBA)-Review on Biomembranes 1376(3):381-390.

Li, H.Y., Y.F. Zhong, S.Y. Wu & N. Shi. 2007. NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert- butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells. Chemical Research in Toxicology 20(9):1242-51.

Lin, T. & M. Morales. 1977. Application of a one-step procedure for measuring inorganic phosphate in the presence of proteins: the actomyosin ATPase system. Analytical Biochemistry 77(1):10-17.

Lowry, O.H., N.J. Rosebrough, A.L. Farr & R.J. Randall. 1951. Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 193(1):265-275.

Madsen, C., M.H. Claesson & C. Ropke. 1996. Immunotoxicity of the pyrethroid insecticides deltametrin and alpha- cypermetrin. Toxicology 107(3):219-227.

Marc, J., O. Mulner-Lorillon, S. Boulben, D, Hureau, G. Durand & R. Belle. 2002. Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation. Chemical Research in Toxicology 15(3):326-331.

Michelangeli, F., M.J. Robson, M.J. East & A.G. Lee. 1990. Fluorescence and kinetic studies of the interactions of pyrethroids with (Ca2+ + Mg2+)-ATPase. Biochimica et Biophysica Acta 1028(1):58-66.

Moya-Quiles, M.R., E. Munoz-Delgado & C.J. Vidal. 1996. Effects of the pyrethroid insecticide permethrin on membrane fluidity. Chemistry and Physics Lipids 79(1):21-28.

Narahashi, T. 1996. Neuronal ion channels as the target sites of insecticides. Pharmacology and Toxicology 79(1):1-14.

Niggli, V., J.T. Penniston & E. Carafoli. 1979. Purification of the (Ca2+-Mg2+)-ATPase from human erythrocyte membranes using a calmodulin affinity column. Journal of Biological Chemistry 254(20):9955-9958.

Plenge-Tellechea, F., F. Soler & F. Fernandez-Belda. 1999. Tricyclic antidepressants inhibit the Ca(2+)-dependent ATPase activity from plasma membrane. Archives of Biochemistry and Biophysics 370(1):119- 125.

Price, N.R. 1976. The effect of two insecticides on the Ca2+ Mg2+ -activated ATPase of the sarcoplasmic reticulum of the flounder, Platichthysflesus. Comp. Biochem. Physiol. C. 55(2):91-94.

Randi, A. S., H.A. Sancovich, A.M. Ferramola de Sancovich, A. Loaiza, L. Krawiec & D.L. Kleiman de Pisarev. 1998. Hexachlorobenzene-induced alterations of rat hepatic microsomal membrane function. Toxicology. 125(2-3):83-94.

Sahib, I.K. & D. Desaiah. 1987. Inhibition of beta-adrenergic stimulated calcium pump of rat cardiac sarcoplasmic reticulum by tricyclohexyltin hydroxide. Cell Biochemistry and Function 5(2):149- 154.

Sahib, I.K., K.S. Prasada Rao & D. Desaiah. 1987. Pyrethroid 2+ inhibition of basal and calmodulin stimulated Ca ATPase and adenylatecyclase in rat brain. Journal of Applied Toxicology 7(2):75-80.

Salas, V. & P.J. Romero. 1996. Effects of trifluralin and oryzalin on the human erythrocyte Ca-ATPase. Pharmacology and Toxicology 78(6):439-440.

Senger, M.R., E.P.Rico, M. de BemArizi, D.B. Rosemberg, R.D. Dias, M.R. Bogo & C.D. Bonan. 2005. Carbofuran and malathion inhibit nucleotide hydrolysis in zebrafish (Danio rerio) brain membranes. Toxicology 212(2-3):107-115.

Soderlund, D. M., J.M. Clark, L. P. Sheets, L.S. Mullin, V.J. Picirillo, D. Sargent, J.T. Stevens & M.L. Weiner. 2002. Mechanisms of pyrethroids neurotoxicity: implications for cumulative risk assessment. Toxicology 171(1):3-59.

Souza, R., P. Cognato, F. Cenci, M.F. S. Rezende, F.V. Thiesen, G. Fauth, M. Reis, C.D. Bonan & R. Dutra. 2003. Different sensitivity of Ca(2+)-ATPase and cholinesterase to pure and commercial pesticides in nervous ganglia of Phyllocaulissoleiformis (Mollusca). Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology 135(2):215-220.

Steinrucken, H.C. & N. Amrhein. 1980. The herbicide glyphosate is a potent inhibitor of 5-enolpyruvyl-shikimic acid- 39-phosphate synthase. Biochemical and Biophysical Research Communications 4(4):1207-1212.

Waku, K. & Y. Nakazawa. 1964. On the lipids of rabbit sarcoplasmic reticulum. The Journal of Biochemistry 56:95-96.

Weiss, B., S. Amler & R.W. Amler. 2004. Pesticides. Pediatrics. 113(Suppl 4):1030-1036.

Zaidi, A., D. Fernandes, J.L. Bean & M.L. Michaelis. (2009). Effects of paraquat-induced oxidative stress on the neuronal plasma membrane Ca(2+)-ATPase. Free Radical Biology and Medicine 47(10):1507-1514.

Cómo citar
Vargas-Medrano, J., Sierra-Fonseca, J. A., Arellano-Carrillo, M., & Plenge-Tellechea, F. (2020). Cypermethrin, deltamethrin and glyphosate affect the activity of the Ca2 +-ATPase from human erythrocyte: Cipermetrina, deltametrina y glifosato afectan la actividad enzimática de la Ca2+-ATPasa de eritrocito humano. TECNOCIENCIA Chihuahua, 5(3), 121-131.