Skip to main content Accessibility help

Maternal low-protein diet in female rat heart: possible protective effect of estradiol

  • G. R. F. Braz (a1), A. S. Emiliano (a1), S. M. Sousa (a1) (a2), A. A. S. Pedroza (a1), D.F. Santana (a1) (a2), M. P. Fernandes (a1), A. I. da Silva (a1) (a2) and C. J. Lagranha (a1) (a2)...


Several studies have shown that maternal low-protein (LP) diet induces detrimental effects in cardiovascular system and oxidative stress in male animals. Additional studies suggested that female has lower incidence of cardiovascular disease. However until present data, the possible effects of estradiol on the undernutrition during gestational and lactation periods are not discussed. The present study was conducted to evaluate the effects of a maternal LP diet during gestational and lactation period on oxidative balance in the female rat hearts ventricles at two ages. Dams were fed with normal protein (NP) or a LP diet during the gestational and lactation period, and their female offspring were divided into age groups (22 or 122 days, corresponding to a low or high estrogen level) composing four experimental groups. Evaluating the nutritional effect showed an increase in oxidative stress biomarkers and decrease in enzymatic defense in LP-22D compared with NP-22D. In contrast, no changes were observed in malondialdehyde and carbonyls, but an increase in glutathione-S-transferase (GST) activity in the LP-122D compared with NP-122D. The global oxy-score in the LP-22D group indicated a predominance of oxidative damage when compared with NP-22D, while in LP-122D group the global oxy-score was restored to NP-122D levels. Evaluating the estradiol effect, our data show a significant decrease in oxidative stress with increase in CAT and GST activity, associated with increase in intracellular thiols. Our data suggest that in situation with low levels of estradiol, hypoproteic diet during gestation and lactation period has detrimental effects on heart, however when estradiol levels raise, the detrimental effects induced are mitigated.


Corresponding author

*Address for correspondence: C. J. Lagranha, Rua Alto do Reservatório, Núcleo de Educação Física e Ciências do Esporte, Bela Vista, Vitória de Santo Antão 55608-680, PE, Brazil. (Email


Hide All

These authors contributed equally to this work.



Hide All
1. Barker, DJ, Forsen, T, Eriksson, JG, Osmond, C. Growth and living conditions in childhood and hypertension in adult life: a longitudinal study. J Hypertens. 2002; 20, 19511956.
2. Barker, DJ, Osmond, C, Kajantie, E, Eriksson, JG. Growth and chronic disease: findings in the Helsinki Birth Cohort. Ann Hum Biol. 2009; 36(5), 445458.
3. Hales, CN, Barker, DJ, Clark, PM, et al. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991; 303, 10191022.
4. Ferreira, DJ, Liu, Y, Fernandes, MP, Lagranha, CJ. Perinatal low-protein diet alters brainstem antioxidant metabolism in adult offspring. Nutr Neurosci. 2016; 19: 369375.
5. Langley-Evans, SC, Phillips, GJ, Jackson, AA. In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr. 1994; 13, 319324.
6. Thornburg, KL. The programming of cardiovascular disease. J Dev Orig Health Dis. 2015; 6, 366376.
7. Barker, DJ, Osmond, C, Golding, J, Kuh, D, Wadsworth, ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298, 564567.
8. Barker, DJ, Osmond, C, Law, CM. The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis. J Epidemiol Community Health. 1989; 43, 237240.
9. Hanson, M, Godfrey, KM, Lillycrop, KA, Burdge, GC, Gluckman, PD. Developmental plasticity and developmental origins of non-communicable disease: theoretical considerations and epigenetic mechanisms. Prog Biophys Mol Biol. 2011; 106, 272280.
10. Eriksson, JG.. Early growth and adult health outcomes--lessons learned from the Helsinki Birth Cohort Study. Matern Child Nutr. 2005; 1, 149154.
11. Ravelli, GP, Stein, ZA, Susser, MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976; 295, 349353.
12. Fleming, TP, Velazquez, MA, Eckert, JJ. Embryos, DOHaD and David Barker. J Dev Orig Health Dis. 2015; 6, 377383.
13. Bai, SY, Briggs, DI, Vickers, MH. Increased systolic blood pressure in rat offspring following a maternal low-protein diet is normalized by maternal dietary choline supplementation. J Dev Orig Health Dis. 2012; 3, 342349.
14. de Brito Alves, JL, Nogueira, VO, de Oliveira, GB, et al. Short- and long-term effects of a maternal low-protein diet on ventilation, O(2)/CO(2) chemoreception and arterial blood pressure in male rat offspring. Br J Nutr. 2014; 111, 606615.
15. Elmes, MJ, Gardner, DS, Langley-Evans, SC. Fetal exposure to a maternal low-protein diet is associated with altered left ventricular pressure response to ischaemia-reperfusion injury. Br J Nutr. 2007; 98, 93100.
16. Bol, V, Desjardins, F, Reusens, B, Balligand, JL, Remacle, C. Does early mismatched nutrition predispose to hypertension and atherosclerosis, in male mice? PLoS One. 2010; 5, e12656.
17. Asopa, S, Cagampang, FR, Anthony, FW, et al. Effect of a low-protein diet during pregnancy on expression of genes involved in cardiac hypertrophy in fetal and adult mouse offspring. J Dev Orig Health Dis. 2010; 1, 371375.
18. Brawley, L, Itoh, S, Torrens, C, et al. Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring. Pediatr Res. 2003; 54, 8390.
19. Sato, S, Mukai, Y, Norikura, T. Maternal low-protein diet suppresses vascular and renal endothelial nitric oxide synthase phosphorylation in rat offspring independent of a postnatal fructose diet. J Dev Orig Health Dis. 2011; 2, 168175.
20. Nascimento, L, Freitas, CM, Silva-Filho, R, et al. The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress. Appl Physiol Nutr Metab. 2014; 39, 880887.
21. Grigore, D, Ojeda, NB, Alexander, BT. Sex differences in the fetal programming of hypertension. Gender Med. 2008; 5(Suppl. A), S121S132.
22. Ozaki, T, Nishina, H, Hanson, MA, Poston, L. Dietary restriction in pregnant rats causes gender-related hypertension and vascular dysfunction in offspring. J Physiol. 2001; 530(Pt 1), 141152.
23. Knowlton, AA, Korzick, DH. Estrogen and the female heart. Mol cell Endocrinol. 2014; 389, 3139.
24. Murphy, E, Steenbergen, C. Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury. Cardiovasc Res. 2007; 75(3), 478486.
25. Sullivan, TR Jr., Karas, RH, Aronovitz, M, et al. Estrogen inhibits the response-to-injury in a mouse carotid artery model. J Clin Invest. 1995; 96, 24822488.
26. Yang, SH, Liu, R, Perez, EJ, et al. Mitochondrial localization of estrogen receptor beta. Proc Natl Acad Sci USA. 2004; 101, 41304135.
27. Hernandez, I, Delgado, JL, Diaz, J, et al. 17beta-estradiol prevents oxidative stress and decreases blood pressure in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol. 2000; 279, R1599R1605.
28. Rodriguez-Rodriguez, P, de Pablo, AL, Condezo-Hoyos, L, et al. Fetal undernutrition is associated with perinatal sex-dependent alterations in oxidative status. J Nutr Biochem. 2015; 26, 16501659.
29. McCall, AL, Han, SJ, Millington, WR, Baum, MJ. Non-saturable transport of [3H]oestradiol across the blood-brain barrier in female rats is reduced by neonatal serum. J Reprod Fertil. 1981; 61, 103108.
30. Zambrano, E, Guzman, C, Rodriguez-Gonzalez, GL, Durand-Carbajal, M, Nathanielsz, PW. Fetal programming of sexual development and reproductive function. Mol Cell Endocrinol. 2014; 382, 538549.
31. Bradford, MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72, 248254.
32. Buege, JA, Aust, SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52, 302310.
33. Levine, RL, Garland, D, Oliver, CN, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990; 186, 464478.
34. Misra, HP, Fridovich, I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972; 247, 31703175.
35. Aebi, H. Catalase in vitro. Methods Enzymol. 1984; 105, 121126.
36. Habig, WH, Pabst, MJ, Fleischner, G, Gatmaitan, Z, Arias, IM, Jakoby, WB. The identity of glutathione S-transferase B with ligandin, a major binding protein of liver. Proc Natl Acad Sci USA. 1974; 71, 38793882.
37. Hissin, PJ, Hilf, R. A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem. 1976; 74(1), 214226.
38. Ellman, GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82, 7077.
39. Kumar, BP, Shivakumar, K. Depressed antioxidant defense in rat heart in experimental magnesium deficiency. Implications for the pathogenesis of myocardial lesions. Biol Trace Elem Res. 1997; 60, 139144.
40. Cavalca, V, Cighetti, G, Bamonti, F, et al. Oxidative stress and homocysteine in coronary artery disease. Clin Chem. 2001; 47, 887892.
41. Touyz, RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension. 2004; 44, 248252.
42. Gioda, CR, de Oliveira Barreto, T, Primola-Gomes, TN, et al. Cardiac oxidative stress is involved in heart failure induced by thiamine deprivation in rats. Am J Physiol Heart Circ Physiol. 2010; 298, H2039H2045.
43. Barp, J, Araujo, AS, Fernandes, TR, et al. Myocardial antioxidant and oxidative stress changes due to sex hormones. Braz J Med Biol Res. 2002; 35, 10751081.
44. Hamed, GM, Bahgat, NM, El-Agaty, SM, Soliman, GZ, Emara, MM. Effects of a soybean protein diet on ovariectomised female albino rats subjected to myocardial infarction. Singapore Med J. 2010; 51, 781789.
45. Munoz-Castaneda, JR, Montilla, P, Munoz, MC, Bujalance, I, Muntane, J, Tunez, I. Effect of 17-beta-estradiol administration during adriamycin-induced cardiomyopathy in ovariectomized rat. Eur J Pharmacol. 2005; 523, 8692.
46. Lagranha, CJ, Deschamps, A, Aponte, A, Steenbergen, C, Murphy, E. Sex differences in the phosphorylation of mitochondrial proteins result in reduced production of reactive oxygen species and cardioprotection in females. Circ Res. 2010; 106, 16811691.
47. Gutteridge, JM. Free radicals in disease processes: a compilation of cause and consequence. Free Radic Res Commun. 1993; 19(3), 141158.
48. de Bem, GF, da Costa, CA, de Oliveira, PR, et al. Protective effect of Euterpe oleracea Mart (acai) extract on programmed changes in the adult rat offspring caused by maternal protein restriction during pregnancy. J Pharm Pharmacol. 2014; 66, 13281338.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed