AFLATOKSİNLERİN ANNE VE ÇOCUK SAĞLIĞINA ETKİLERİ

Aflatoksinler Aspergillus türevleri tarafından üretilen sekonder metabolitlerdir. İnsanların aflatoksin maruziyeti genel olarak aflatoksin ile kontamine olmuş besinlerin tüketiminden kaynaklanmaktadır. Aflatoksinlerin; belirlenmiş miktarların üzerinde alınmasının insan sağlığı üzerine olumsuz etkilerinin olduğu birçok çalışma ile gösterilmiştir. Bu olumsuz etkiler vücutta birçok farklı patolojik durumun gelişiminde etkili olabilmektedir ancak etki mekanizmaları bireyin metabolik durumuna, alınan türe ve doza bağlı olarak değişmektedir. Yetişkin bireylerde aflatoksin maruziyetinin etkilerine yönelik yapılmış birçok çalışma bulunurken maternal aflatoksin maruziyetinin anne ve çocuk üzerindeki etkilerine yönelik yapılmış çalışmalar oldukça sınırlıdır. Yapılan insan ve hayvan çalışmaları sonucu genel olarak maternal aflatoksin maruziyetinin; gebelikte maternal anemi, mikro besin ögesi eksiklikleri, proinflamatuar sitokinlerin artması ve oksidatif stresin artması gibi maternal komplikasyonlarının bulunduğu bildirilmektedir. Maternal artmış proinflamatuar durumun ise ileride birçok kronik hastalığın oluşması ile ilişkili olduğu bildirilmektedir. Gebelik dönemindeki maternal aflatoksin maruziyetinin aynı zamanda fetüs ve yenidoğan üzerinde de olumsuz etkileri bulunmaktadır. Vücutta güvenilir seviyelerin üzerindeki aflatoksin maruziyetinin, plasental yetmezliğe sebep olduğu, fetal büyüme ve gelişmeyi olumsuz etkilediği, yenidoğan sarılığına sebep olabileceği bildirilmektedir. Aflatoksinin intrauterin büyüme ve gelişmeyi olumsuz etkileme mekanizmalarının arasında; enteropatiye sebep olması, immün sistemi baskılaması ve insülin benzeri büyüme faktörü salınımını azaltması gösterilmekle birlikte ayrıca annenin aflatoksin maruziyetinin erken çocukluk dönemi bodurluğu ile ilişkili olabileceği bildirilmektedir. Ancak yapılmış çalışmaların büyük kısmının hayvan çalışmaları ve in vitro çalışma olması, ileriye dönük epidemiyolojik insan çalışmaların sınırlı olması sebebi ile maternal aflatoksin maruziyetinin anne ve çocuk sağlığına etkileri henüz tam olarak bilinememektedir. Özellikle gelişmekte olan ülkelerdeki yaygın maruziyet göz önüne alındığında, olumsuz gebelik sonuçlarında aflatoksinin rolü için daha güçlü kanıtlar sağlamak oldukça önemlidir. Bu derleme yazının amacı maternal aflatoksin maruziyetinin anne ve çocuk sağlığına etkilerinin güncel bilgiler eşliğinde tartışılmasıdır.

Anahtar Kelimeler:

aflatoksin, mantar, kontaminasyon, maternal sağlık, fetal sağlık

EFFECTS OF AFLATOXINS ON MATERNAL AND CHILD HEALTH

Aflatoxins are secondary metabolites produced by Aspergillus derivatives. Human exposure to aflatoxin generally results from the consumption of foods contaminated with aflatoxin.; It has been shown in many studies that taking aflatoxins more than the specified amounts has negative effects on human health. These negative effects may play a role in the development of many different pathological conditions in the body, but the mechanisms of action vary depending on the individual's metabolic state, the species taken and the dose. While there are many studies on the effects of aflatoxin exposure in adult individuals, studies on the effects of maternal aflatoxin exposure on the mother and child are quite limited. As a result of human and animal studies, maternal aflatoxin exposure in general; It is reported that there are maternal complications such as maternal anemia, micronutrient deficiencies, increased proinflammatory cytokines and increased oxidative stress during pregnancy. It has been reported that the increased maternal proinflammatory status is associated with the formation of many chronic diseases in the future. Maternal aflatoxin exposure during pregnancy also has negative effects on the fetus and newborn. It has been reported that aflatoxin exposure above safe levels in the body causes placental insufficiency, adversely affects fetal growth and development, and may cause neonatal jaundice. Among the mechanisms that aflatoxin negatively affecting intrauterine growth and development; Although it has been shown to cause enteropathy, suppress the immune system and reduce the release of insulin-like growth factors, it is has also been reported that maternal aflatoxin exposure may be associated with early childhood stunting. However, the effects of maternal aflatoxin exposure on maternal and child health are not yet fully known due to the fact that most of the studies are animal studies and in vitro studies, and the prospective epidemiological human studies are limited. It is essential to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, especially given the widespread exposure in developing countries. The purpose of this review article is to discuss the effects of maternal aflatoxin exposure on maternal and child health in the light of current information.

Keywords:

Aflatoxin, Fungal, Contamination,

PDF

___

1. (JECFA). Evaluation of certain contaminants in food: eighty-third report of the joint FA. https://apps.who.int/iris/handle/10665/254893, Erişim tarihi: 23.05.2020.
2. Pitt J, Wild C, Gelderblom W, et al. Improving public health through mycotoxin control. World Health. 2012;158: 162.
3. Wild CP, Miller JD, Groopman JD. Mycotoxin Control in Low-and Middle-income Countries. https://www.ncbi.nlm.nih.gov/books/NBK350558/, Erişim Tarihi: 23.05.2020.
4. International Agency for Research on Cancer (IARC). IARC monograph on the evaluation of carcinogenic risks to humans. http://monographs.iarc.fr/ENG/ Monographs/vol100F/mono100F-23.pdf, Erişim Tarihi: 24.05.2020.
5. Soyöz M, Özçelik N. Okratoksin A'nın toksik etkileri ve eliminasyonu. Türkiye Klinikleri Journal of Medical Science. 2002;22: 421.
6. Benkerroum N. Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action. Int J Environ Res Public Health. 2020;17: 423.
7. Shuaib FM, Jolly PE, Ehiri JE, et al. Association between anemia and aflatoxin B1 biomarker levels among pregnant women in Kumasi, Ghana. Am J Trop Med Hyg. 2010;83:1077-1083.
8. Smith LE, Prendergast AJ, Turner PC, et al. Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes. Am J Trop Med Hyg. 2017;96(4):770 – 776.
9. Watson S, Gong YY, Routledge M. Interventions Targeting Child Undernutrition in Developing Countries May Be Undermined by Dietary Exposure to Aflatoxin. Crit Rev Food Sci Nutr. 2017;111:217-220.
10. Eze UA, Routledge MN, Okonofua FE, et al. Mycotoxin exposure and adverse reproductive health outcomes in Africa: a review. World Mycotoxin J. 2018;1-20.
11. Alamu EO, Gondwe T, Akello J, et al. Relationship between serum aflatoxin concentrations and the nutritional status of children aged 6–24 months from Zambia. Int J Food Sci Nutr. 2019;71(5):593-603.
12. Kyei NNA, Boakye D, Gabryrsch S. Maternal mycotoxin exposure ad adverse pregnancy outcomes: a systematic review. Mycotoxin Res. 2020;36:243–255.
13. Turner PC, Collinson AC, Cheung YB, et al. Aflatoxin exposure in utero causes growth faltering in Gambian infants. Int J Epidemiol. 2007;36:1119–1125.
14. Shuaib FM, Jolly PE, Ehiri JE, et al. Association between anemia and aflatoxin B1 biomarker levels among pregnant women in Kumasi, Ghana. Am J Trop Med Hyg. 2010;83:1077–1083.
15. Piekkola S, Turner PC, Abdel-Hamid M et al. Characterisation of aflatoxin and deoxynivalenol exposure among pregnant Egyptian women. Food Addit Contam. 2012;29:962- 971.
16. Smith LE, Mbuya MN, Prendergast AJ et al. Determinants of recent aflatoxin exposure among pregnant women in rural Zimbabwe. Molecular Nutrition and Food Research. 2017;61:1601049.
17. Groopman JD, Egner PA, Schulze KJ et al. Aflatoxin exposure during the first 1000 days of life in rural south Asia assessed by aflatoxin B-lysine albumin biomarkers. Food Chem Toxicol. 2014;9:00417–7.
18. Andretta I, Kipper M, Lehnen CR, Lovatto PA. Meta-analysis of the relationship of mycotoxins with biochemical and hematological parameters in broilers. Poult Sci. 2012;91: 376–382.
19. Eisa AMA, Metwally AY. Effect of glucomannan on haematological, coagulation and biochemical parameters in male rabbits fed aflatoxin-contaminated ration. World Mycotoxin J. 2011;4: 183–188.
20. Nemeth E, Rivera S, Gabayan V, et al. Il-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113:1271–1276.
21. Qian GQ, Tang LL, Guo X et al. Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male f344 rats. J Appl Toxicol. 2014;34:241–249.
22. Wan XL, Yang ZB, Yang WR, et al. Toxicity of increasing aflatoxin B1 concentrations from contaminated corn with or without clay adsorbent supplementation in ducklings. Poult Sci. 2013;92:1244–1253.
23. Gong YY, Wilson S, Mwatha JK et al. Aflatoxin exposure may contribute to chronic hepatomegaly in Kenyan school children. Environ Health Perspect. 2012;120:893–896.
24. Abdulrazzaq YM, Osman N, Yousif ZM, Trad O. Morbidity in neonates of mothers who have ingested aflatoxins. Ann Trop Paediatr. 2004;24(2):145‐151.
25. Shuaib FM, Jolly PE, Ehiri JE et al. Association between birth outcomes and aflatoxin B1 biomarker blood levels in pregnant women in Kumasi, Ghana. Trop Med Int Health. 2010;15:160-167.
26. Gong YY, Torres-Sanchez L, Lopez-Carrillo L et al. Association between tortilla consumption and human urinary fumonisin B1 levels in a Mexican population. Cancer Epidemiol Biomarkers Prev. 2008;17: 688-694.
27. Bondy GS, Pestka JJ. Immunomodulation by fungal toxins. J Toxicol Environ Health B Crit Rev. 2000;3:109–143.
28. Turner PC, Moore SE, Hall AJ, et al. Modification of immune function through exposure to dietary aflatoxin in Gambian children. Environ Health Perspect. 2003;111:217–220.
29. Jiang Y, Jolly PE, Ellis WO et al. Aflatoxin B1 albumin adduct levels and cellular immune status in Ghanaians. Int Immunol. 2005;17:807–814.
30. Castelino JM, Routledge MN, Wilson S, et al. Aflatoxin exposure is inversely associated with IGF1 and IGFBP3 levels in vitro and in Kenyan schoolchildren. Molecular Nutrition and Food Research. 2015;59: 574-581.
31. Gong YY, Cardwell K, Hounsa A et al. Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. Br Med J. 2002; 325(7354): 20-1.
32. Gong YY, Hounsa A, Egal S et al. Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa. Environ Health Perspect. 2004;112(13): 1334-8.
33. Mahdavi R, Nikniaz L, Arefhosseini SR et al. Determination of aflatoxin M1 in breast Milk samples in Tabriz-Iran. Matern Child Health J. 2010;14:141-145.
34. McMillan A, Renaud JB, Burgess KMN et al. Aflatoxin exposure in Nigerian children with severe acute malnutrition. Food Chem Toxicol. 2018;111:356–362.
35. Hernandez‐Vargas H, Castelino J, Silver MJ, et al. Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia. Int J Epidemiol. 2015;44: 1238–1248.
36. Gong YY, Egal S, Hounsa A, et al. Determinants of aflatoxin exposure in young children from Benin and Togo, West Africa: the critical role of weaning. Int J Epidemiol. 2003;32(4):556‐562.
37. Makori N, Matemu A, Kimanya M, et al. Inadequate management of complementary foods contributes to the risk of aflatoxin exposure and low nutrition status among children. World Mycotoxin J. 2019;12(1):67-76.
38. Khlangwiset P, Shephard GS, Wu F. Aflatoxins and growth impairment: a review. Crit Rev Toxicol. 2011;41: 740–755.
39. Thibeau S, D’Apolito K. Review of the relationships between maternal charactersitics and preterm breastmilk immune components. Biol Res Nurs. 2012;14:207–216.
40. Karayagiz Muslu G, Ozdemir M. Occurrence of and Factors Associated With the Presence of Aflatoxin M1 in Breast Milk of Mothers in Fethiye, Turkey. Biol Res Nurs. 2020;22(3): 362–368.
41. United Nations. Progress towards the sustainable development goals. https://unstats.un.org/sdgs/files/report/2016/secretary-general-sdg-report-2016- -EN.pdf, Erişim Tarihi: 25.05.2020.
42. World Health Organization (WHO). Global nutrition targets 2025: Stunting policy brief. https://apps.who.int/iris/bitstream/handle/10665/149019/WHO_NMH_NHD_14.3_eng.pdf?sequence=1&isAllowed=y, Erişim Tarihi: 25.05.2020.
43. Mupunga I, Mngqawa P, Katerere D. Peanuts, Aflatoxins and Undernutrition in Children in Sub-Saharan Africa. Nutrients. 2017;9(12): 1287.
44. Wild CP, Hall AJ. Primary prevention of hepatocellular carcinoma in developing countries. Mutat Res. 2000;462(2-3): 381-93.
45. Omara T, Nassazi W, Omute T et al. Aflatoxins in Uganda: An Encyclopedic Review of the Etiology, Epidemiology, Detection, Quantification, Exposure Assessment, Reduction, and Control. International Journal of Microbiology. 2019;4723612.
46. Andrews-Trevino JY, Webb P, Shively G. Dietary determinants of aflatoxin B1-lysine adduct in pregnant women consuming a rice-dominated diet in Nepal. Eur J Clin Nutr. 2020;74:732–740.
47. Peltonen K, El-Nezami H, Haskard C, et al. Aflatoxin B1 binding by dairy strains of lactic acid bacteria and bifidobacteria. J Dairy Sci. 2001;84(10):2152-6.
48. Wacoo A, Mukisa I, Meeme R et al. Probiotic Enrichment and Reduction of Aflatoxins in a Traditional African Maize-Based Fermented Food. Nutrients. 2019;11(2): 265.
49. Assaf JC, Atoui A, Khoury AE, Chokr A, Louka N. A comparative study of procedures for binding of aflatoxin M1 to Lactobacillus rhamnosus GG. Brazilian Journal of Microbiology. 2018;49(1):120–127.
50. Chen Y, Li R, Chang Q et al. Lactobacillus bulgaricus or Lactobacillus rhamnosus Suppresses NF-κB Signaling Pathway and Protects against AFB1-Induced Hepatitis: A Novel Potential Preventive Strategy for Aflatoxicosis? Toxins. 2019;11(1):17.