Skip to main content

Advertisement

Log in

Docosahexaenoic Acid (DHA, C22:6, ω-3) Composition of Milk and Mammary Gland Tissues of Lactating Mother Rats Is Severely Affected by Lead (Pb) Exposure

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Docosahexaenoic acid (DHA, C22:6, ω-3), an ω-3 polyunsaturated fatty acid (PUFA), is critical for brain growth, development, and cognitive ability. It is consumed by offspring via milk during lactation. However, the toxic heavy metal lead (Pb) readily passes into the mammary glands of mother animals and then to offspring through milk. Here, we investigated whether DHA composition of milk and mammary gland tissues is affected by Pb exposure. Mother rats were exposed to Pb via drinking water (0.1%). The fatty acid profile and levels of reduced glutathione (GSH), lipid peroxide (LPO), and pro-inflammatory TNF-α in milk and mammary tissues were measured. Levels of DHA and antioxidant GSH decreased (P < 0.05), while LPO and TNF-α levels increased (P < 0.05) both in milk and mammary tissues. Our results suggest that toxic Pb exposure can upset the level of milk DHA, which may affect brain growth and development, and hence cognitive ability in adulthood and later life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig 1
Fig 2
Fig 3
Fig 4

Similar content being viewed by others

References

  1. Kawakita E, Hashimoto M, Shido O (2006) Docosahexaenoic acid promotes neurogenesis in vitro and in vivo. Neuroscience 139:991–997. https://doi.org/10.1016/j.neuroscience.2006.01.021

    Article  CAS  PubMed  Google Scholar 

  2. Oster T, Pillot T (2010) Docosahexaenoic acid and synaptic protection in Alzheimer’s disease mice. Biochim Biophys Acta 1801(8):791–798. https://doi.org/10.1016/j.bbalip.2010.02.011

    Article  CAS  PubMed  Google Scholar 

  3. Tanaka K, Farooqui AA, Siddiqi NJ et al (2012) Effects of docosahexaenoic acid on neurotransmission. Biomol Ther (Seoul) 20:152–157. https://doi.org/10.4062/biomolther.2012.20.2.152

    Article  CAS  Google Scholar 

  4. Bradbury J (2011) Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain. Nutrients 3:529–554. https://doi.org/10.3390/nu3050529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hashimoto M, Hossain S, Al Mamun A et al (2017) Docosahexaenoic acid: one molecule diverse functions. Crit Rev Biotechnol 37:579–597. https://doi.org/10.1080/07388551.2016.1207153

    Article  CAS  PubMed  Google Scholar 

  6. Hashimoto M, Hossain MS, Yamasaki H et al (1999a) Effects of eicosapentaenoic acid and docosahexaenoic acid on plasma membrane fluidity of aortic endothelial cells. Lipids 34:1297–1304. https://doi.org/10.1007/s11745-999-0481-6

    Article  CAS  PubMed  Google Scholar 

  7. Hashimoto M, Hossain MS, Shimada T et al (2001) Effects of docosahexaenoic acid on annular lipid fluidity of the rat bile canalicular plasma membrane. J Lipid Res 42(7):1160–1168

    CAS  PubMed  Google Scholar 

  8. Hashimoto M, Hossain S, Shimada T, Shido O (2006) Docosahexaenoic acid-induced protective effect against impaired learning in amyloid beta-infused rats is associated with increased synaptosomal membrane fluidity. Clin Exp Pharmacol Physiol 33:934–939. https://doi.org/10.1111/j.1440-1681.2006.04467.x

    Article  CAS  PubMed  Google Scholar 

  9. Hashimoto M, Hossain S, Shido O (2006) Docosahexaenoic acid but not eicosapentaenoic acid withstands dietary cholesterol-induced decreases in platelet membrane fluidity. Mol Cell Biochem 293:1–8. https://doi.org/10.1007/s11010-006-0164-x

    Article  CAS  PubMed  Google Scholar 

  10. Onuki Y, Morishita M, Chiba Y, Tokiwa S, Takayama K (2006) Docosahexaenoic acid and eicosapentaenoic acid induce changes in the physical properties of a lipid bilayer model membrane. Chem Pharm Bull (Tokyo) 54(1):68–71. https://doi.org/10.1248/cpb.54.68

    Article  CAS  Google Scholar 

  11. Brenner RR (1984) Effect of unsaturated acids on membrane structure and enzyme kinetics. Prog Lipid Res 23:69–96. https://doi.org/10.1016/0163-7827(84)90008-0

    Article  CAS  PubMed  Google Scholar 

  12. Kim H-Y, Spector AA, Xiong Z-M (2011) A synaptogenic amide N-docosahexaenoylethanolamide promotes hippocampal development. Prostaglandins Other Lipid Mediat 96:114–120. https://doi.org/10.1016/j.prostaglandins.2011.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Suzuki H, Manabe S, Wada O, Crawford MA (1997) Rapid incorporation of docosahexaenoic acid from dietary sources into brain microsomal, synaptosomal and mitochondrial membranes in adult mice. Int J Vitam Nutr Res 67:272–278

    CAS  PubMed  Google Scholar 

  14. Salem NJ, Litman B, Kim HY, Gawrisch K (2001) Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 36:945–959. https://doi.org/10.1007/s11745-001-0805-6

    Article  CAS  PubMed  Google Scholar 

  15. Bazan NG (2009) Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer’s disease. J Lipid Res 50(Suppl):S400–S405. https://doi.org/10.1194/jlr.R800068-JLR200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Molloy C, Doyle LW, Makrides M, Anderson PJ (2012) Docosahexaenoic acid and visual functioning in preterm infants: a review. Neuropsychol Rev 22:425–437. https://doi.org/10.1007/s11065-012-9216-z

    Article  PubMed  Google Scholar 

  17. Su H-M (2010) Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance. J Nutr Biochem 21:364–373. https://doi.org/10.1016/j.jnutbio.2009.11.003

    Article  CAS  PubMed  Google Scholar 

  18. Gamoh S, Hashimoto M, Hossain S, Masumura S (2001) Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats. Clin Exp Pharmacol Physiol 28:266–270. https://doi.org/10.1046/j.1440-1681.2001.03437.x

    Article  CAS  PubMed  Google Scholar 

  19. Gamoh S, Hashimoto M, Sugioka K et al (1999) Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats. Neuroscience 93:237–241

    Article  CAS  PubMed  Google Scholar 

  20. Jensen CL, Lapillonne A (2009) Docosahexaenoic acid and lactation. Prostaglandins Leukot Essent Fat Acids 81:175–178. https://doi.org/10.1016/j.plefa.2009.05.006

    Article  CAS  Google Scholar 

  21. Hashimoto M, Hossain S, Shimada T et al (2002) Docosahexaenoic acid provides protection from impairment of learning ability in Alzheimer’s disease model rats. J Neurochem 81:1084–1091. https://doi.org/10.1046/j.1471-4159.2002.00905.x

    Article  CAS  PubMed  Google Scholar 

  22. Söderberg M, Edlund C, Kristensson K, Dallner G (1991) Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids 26:421–425. https://doi.org/10.1007/BF02536067

    Article  PubMed  Google Scholar 

  23. Ip MM, Shoemaker SF, Darcy KM (1992) Regulation of rat mammary epithelial cell proliferation and differentiation by tumor necrosis factor-alpha. Endocrinology 130:2833–2844. https://doi.org/10.1210/endo.130.5.1572296

    Article  CAS  PubMed  Google Scholar 

  24. Goldman AS, Chheda S, Garofalo R, Schmalstieg FC (1996) Cytokines in human milk: properties and potential effects upon the mammary gland and the neonate. J Mammary Gland Biol Neoplasia 1:251–258

    Article  CAS  PubMed  Google Scholar 

  25. Holman RT (1986) Control of polyunsaturated acids in tissue lipids. J Am Coll Nutr 5:183–211

    Article  CAS  PubMed  Google Scholar 

  26. Agostoni C, Marangoni F, Stival G et al (2008) Whole blood fatty acid composition differs in term versus mildly preterm infants: small versus matched appropriate for gestational age. Pediatr Res 64:298–302. https://doi.org/10.1203/PDR.0b013e31817d9c23

    Article  CAS  PubMed  Google Scholar 

  27. Yang X, Sheng W, Sun GY, Lee JC-M (2011) Effects of fatty acid unsaturation numbers on membrane fluidity and alpha-secretase-dependent amyloid precursor protein processing. Neurochem Int 58:321–329. https://doi.org/10.1016/j.neuint.2010.12.004

    Article  CAS  PubMed  Google Scholar 

  28. Bakulski KM, Rozek LS, Dolinoy DC et al (2012) Alzheimer’s disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics. Curr Alzheimer Res 9:563–573. https://doi.org/10.2174/156720512800617991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Singh PK, Singh MK, Yadav RS et al (2017) Omega-3 fatty acid attenuates oxidative stress in cerebral cortex, cerebellum, and hippocampus tissue and improves neurobehavioral activity in chronic lead-induced neurotoxicity. Nutr Neurosci 22(2):83–97. 1–15. https://doi.org/10.1080/1028415X.2017.1354542

    Article  PubMed  Google Scholar 

  30. Hossain MS, Hashimoto M, Gamoh S, Masumura S (1999) Antioxidative effects of docosahexaenoic acid in the cerebrum versus cerebellum and brainstem of aged hypercholesterolemic rats. J Neurochem 72:1133–1138. https://doi.org/10.1046/j.1471-4159.1999.0721133.x

    Article  CAS  PubMed  Google Scholar 

  31. Jarrar BM, Taib NT (2012) Histological and histochemical alterations in the liver induced by lead chronic toxicity. Saudi J Biol Sci 19:203–210. https://doi.org/10.1016/j.sjbs.2011.12.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sharma S, Singh B (2014) Effects of acute and chronic lead exposure on kidney lipid peroxidation and antioxidant enzyme activities in BALB-C mice (Mus musculus). Int J Sci Res 3:1564–1566. www.ijsr.net: Paper ID: SEP1442

    Google Scholar 

  33. Aldahmash BA, El-Nagar DM (2016) Antioxidant effects of captopril against lead acetate-induced hepatic and splenic tissue toxicity in Swiss albino mice. Saudi J Biol Sci 23:667–673. https://doi.org/10.1016/j.sjbs.2016.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kilikdar D, Mukherjee D, Mitra E et al (2011) Protective effect of aqueous garlic extract against lead-induced hepatic injury in rats. Indian J Exp Biol 49:498–510

    PubMed  Google Scholar 

  35. Gurer H, Ozgunes H, Neal R et al (1998) Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats. Toxicology 128:181–189. https://doi.org/10.1016/S0300-483X(98)00074-2

    Article  CAS  PubMed  Google Scholar 

  36. Apostoli P, Kiss P, Porru S et al (1998) Male reproductive toxicity of lead in animals and humans. ASCLEPIOS Study Group. Occup Environ Med 55:364–374. https://doi.org/10.1136/oem.55.6.364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cecil KM, Brubaker CJ, Adler CM et al (2008) Decreased brain volume in adults with childhood lead exposure. PLoS Med 5:e112. https://doi.org/10.1371/journal.pmed.0050112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Verina T, Rohde CA, Guilarte TR (2007) Environmental lead exposure during early life alters granule cell neurogenesis and morphology in the hippocampus of young adult rats. Neuroscience 145:1037–1047. https://doi.org/10.1016/j.neuroscience.2006.12.040

    Article  CAS  PubMed  Google Scholar 

  39. Hossain S, Bhowmick S, Jahan S et al (2016) Maternal lead exposure decreases the levels of brain development and cognition-related proteins with concomitant upsurges of oxidative stress, inflammatory response and apoptosis in the offspring rats. Neurotoxicology 56:150–158. https://doi.org/10.1016/j.neuro.2016.07.013

    Article  CAS  PubMed  Google Scholar 

  40. Hashimoto M, Shinozuka K, Gamoh S, Tanabe Y, Hossain SMS, Kwon Y, Hata N, Misawa Y, Kunimoto M, Masumura S (1999) The hypotensive effect of docosahexaenoic acid is associated with the enhanced release of ATP from the caudal artery of aged rats. J Nutr 129:70–76. https://doi.org/10.1093/jn129.1.70

    Article  CAS  PubMed  Google Scholar 

  41. Hashimoto M, Hossain S, Katakura M et al (2015) The binding of Abeta1-42 to lipid rafts of RBC is enhanced by dietary docosahexaenoic acid in rats: Implicates to Alzheimer’s disease. Biochim Biophys Acta 1848:1402–1409. https://doi.org/10.1016/j.bbamem.2015.03.008

    Article  CAS  PubMed  Google Scholar 

  42. Etem-Piskin I, Nur Karavar H, Arasli M, Ermis B (2012) Effect of maternal smoking on colostrum and breast milk cytokines. Eur Cytokine Netw 23:187–190. https://doi.org/10.1684/ecn.2013.0324

    Article  CAS  PubMed  Google Scholar 

  43. Lehtolainen T, Rontved C, Pyorala S (2004) Serum amyloid A and TNF alpha in serum and milk during experimental endotoxin mastitis. Vet Res 35:651–659. https://doi.org/10.1051/vetres:2004043

    Article  CAS  PubMed  Google Scholar 

  44. Hossain S, Bhowmick S, Islam S et al (2015) Oral administration of Ganoderma lucidum to lead-exposed rats protects erythrocytes against hemolysis: implicates to anti-anemia. Evidence-based Complement Altern Med 2015:8. https://doi.org/10.1155/2015/463703

    Article  Google Scholar 

  45. Halliwell B, Gutteridge JMC (1989) Protection against oxidants in biological systems: the superoxide theory of oxygen toxicity. In: Halliwell B, Gutteridge JMC (eds) Free Radical in Biology and Medicine. Clarendon Press, Oxford, pp 86–123

    Google Scholar 

  46. Yiin SJ, Lin TH (1995) Lead-catalyzed peroxidation of essential unsaturated fatty acid. Biol Trace Elem Res 50:167–172. https://doi.org/10.1007/BF02789419

    Article  CAS  PubMed  Google Scholar 

  47. Hossain MS, Hashimoto M, Masumura S (1998) Influence of docosahexaenoic acid on cerebral lipid peroxide level in aged rats with and without hypercholesterolemia. Neurosci Lett 244:157–160. https://doi.org/10.1016/S0304-3940(98)00147-5

    Article  CAS  PubMed  Google Scholar 

  48. Egan RW, Paxton J, Kuehl FAJ (1976) Mechanism for irreversible self-deactivation of prostaglandin synthetase. J Biol Chem 251:7329–7335

    CAS  PubMed  Google Scholar 

  49. Zimmermann L, Pages N, Antebi H et al (1993) Lead effect on the oxidation resistance of erythrocyte membrane in rat triton-induced hyperlipidemia. Biol Trace Elem Res 38:311–318. https://doi.org/10.1007/BF02785314

    Article  CAS  PubMed  Google Scholar 

  50. Knowles SO, Donaldson WE, Andrews JE (1998) Changes in fatty acid composition of lipids from birds, rodents, and preschool children exposed to lead. Biol Trace Elem Res 61:113–125. https://doi.org/10.1007/BF02784024

    Article  CAS  PubMed  Google Scholar 

  51. Osterode W, Ulberth F (2000) Increased concentration of arachidonic acid in erythrocyte membranes in chronically lead-exposed men. J Toxicol Environ Health Part A 59(2):87–95. https://doi.org/10.1080/009841000156998

    Article  CAS  Google Scholar 

  52. Adegbesan BO, Adenuga GA (2007) Effect of lead exposure on liver lipid peroxidative and antioxidant defense systems of protein-undernourished rats. Biol Trace Elem Res 116:219–225. https://doi.org/10.1007/BF02685932

    Article  CAS  PubMed  Google Scholar 

  53. Wang J, Wu J, Zhang Z (2006) Oxidative stress in mouse brain exposed to lead. Ann Occup Hyg 50:405–409. https://doi.org/10.1093/annhyg/mei079

    Article  CAS  PubMed  Google Scholar 

  54. Kasperczyk S, Slowinska-Lozynska L, Kasperczyk A et al (2015) The effect of occupational lead exposure on lipid peroxidation, protein carbonylation, and plasma viscosity. Toxicol Ind Health 31:1165–1171. https://doi.org/10.1177/0748233713491804

    Article  CAS  PubMed  Google Scholar 

  55. Patra RC, Rautray AK, Swarup D (2011) Oxidative stress in lead and cadmium toxicity and its amelioration. Vet Med Int 2011:457327. https://doi.org/10.4061/2011/457327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cheng Y-J, Yang B-C, Liu M-Y (2006) Lead increases lipopolysaccharide-induced liver-injury through tumor necrosis factor-alpha overexpression by monocytes/macrophages: role of protein kinase C and P42/44 mitogen-activated protein kinase. Environ Health Perspect 114:507–513. https://doi.org/10.1289/ehp.8550

    Article  CAS  PubMed  Google Scholar 

  57. Liu B, Zupan B, Laird E et al (2014) Maternal hematopoietic TNF, via milk chemokines, programs hippocampal development and memory. Nat Neurosci 17:97–105. https://doi.org/10.1038/nn.3596

    Article  CAS  PubMed  Google Scholar 

  58. Hashimoto M, Hossain S, Katakura M et al (2018) Docosahexaenoic acid helps to lessen extinction memory in rats. Molecules 23:E451. https://doi.org/10.3390/molecules23020451

    Article  CAS  PubMed  Google Scholar 

  59. Sidhu VK, Huang BX, Desai A et al (2016) Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome. Neurobiol Aging 41:73–85. https://doi.org/10.1016/j.neurobiolaging.2016.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Jiang L-H, Yan S, Wang J, Liang Q (2013) Oral administration of docosahexaenoic acid activates the GDNF-MAPK-CERB pathway in hippocampus of natural aged rat. Pharm Biol 51:1188–1195. https://doi.org/10.3109/13880209.2013.784341

    Article  CAS  PubMed  Google Scholar 

  61. Ramirez-Ramirez V, Macias-Islas MA, Ortiz GG et al (2013) Efficacy of fish oil on serum of TNF alpha, IL-1 beta , and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b. Oxidative Med Cell Longev 2013:709493. https://doi.org/10.1155/2013/709493

    Article  CAS  Google Scholar 

  62. Anderson DW, Mettil W, Schneider JS (2016) Effects of low level lead exposure on associative learning and memory in the rat: influences of sex and developmental timing of exposure. Toxicol Lett 246:57–64. https://doi.org/10.1016/j.toxlet.2016.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. de Oliveira FS, Viana MR, Antoniolli AR, Marchioro M (2001) Differential effects of lead and zinc on inhibitory avoidance learning in mice. Brazilian J Med Biol Res = Rev Bras Pesqui medicas e Biol 34:117–120

    Article  Google Scholar 

  64. Krol E, Redman P, Thomson PJ et al (2005) Effect of photoperiod on body mass, food intake and body composition in the field vole, Microtus agrestis. J Exp Biol 208:571–584. https://doi.org/10.1242/jeb.01429

    Article  CAS  PubMed  Google Scholar 

  65. Valdearcos M, Robblee MM, Benjamin DI et al (2014) Microglia dictate the impact of saturated fat consumption on hypothalamic inflammation and neuronal function. Cell Rep 9:2124–2138. https://doi.org/10.1016/j.celrep.2014.11.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Gibson RA, Muhlhausler B, Makrides M (2011) Conversion of linoleic acid and alpha-linolenic acid to long-chain polyunsaturated fatty acids (LCPUFAs), with a focus on pregnancy, lactation and the first 2 years of life. Matern Child Nutr 7(Suppl 2):17–26. https://doi.org/10.1111/j.1740-8709.2011.00299.x

    Article  PubMed  PubMed Central  Google Scholar 

  67. Innis SM (2011) Metabolic programming of long-term outcomes due to fatty acid nutrition in early life. Matern Child Nutr 7(Suppl 2):112–123. https://doi.org/10.1111/j.1740-8709.2011.00318.x

    Article  PubMed  PubMed Central  Google Scholar 

  68. Massiera F, Guesnet P, Ailhaud G (2006) The crucial role of dietary n-6 polyunsaturated fatty acids in excessive adipose tissue development: relationship to childhood obesity. Nestle Nutr Workshop Ser Pediatr Program 57:235. https://doi.org/10.1159/000091076

    Article  CAS  PubMed  Google Scholar 

  69. Hauner H, Brunner S, Amann-Gassner U (2013) The role of dietary fatty acids for early human adipose tissue growth. Am J Clin Nutr 98:549S–555S. https://doi.org/10.3945/ajcn.112.040733

    Article  CAS  PubMed  Google Scholar 

  70. Muhlhausler BS, Gibson RA, Makrides M (2011) The effect of maternal omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation during pregnancy and/or lactation on body fat mass in the offspring: a systematic review of animal studies. Prostaglandins Leukot Essent Fat Acids 85:83–88. https://doi.org/10.1016/j.plefa.2011.04.027

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the contribution of the University Grant Commission-Higher Education Quality Enhancement Program (UGC-HEQEP) for the partial instrumental support (CP-358).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shahdat Hossain.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hossain, S., Hussain, J., Bhowmick, S. et al. Docosahexaenoic Acid (DHA, C22:6, ω-3) Composition of Milk and Mammary Gland Tissues of Lactating Mother Rats Is Severely Affected by Lead (Pb) Exposure. Biol Trace Elem Res 195, 525–534 (2020). https://doi.org/10.1007/s12011-019-01878-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-019-01878-1

Keywords

Navigation