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EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY

Year 2022, Volume: 85 Issue: 3, 433 - 439, 06.07.2022
https://doi.org/10.26650/IUITFD.1074354

Abstract

Objective: Melamine (mel), which is illegally added to formula to providing false-positive protein content, has caused acute renal failure in infants due to crystal formation. This study aimed to investigate the nephrotoxic effects of chronic low-dose mel exposure from the weaning period (supplementary food period).
Materials and Methods: Eighteen female rats in the weaning period (21-days-old) were divided into three groups. A 0.1 ml saline was given to the control group by oral gavage (p.o). Fifty mg/kg mel was given to the second group and 75 mg/kg mel to the third group dissolved in 0.1 ml saline for twenty one days p.o.. At the end of the experiment, the animals were sacrificed, and histopathologic, morphometric, and ultrastructural analysis were performed on kidney tissues.
Results: There was an inflammatory cell infiltration in the tubulointerstitial area, and no crystal formation was observed in either of the mel groups. In the 75 mg mel group, glomerular and tubular epithelial damage and significant increases in Bowman’s space were observed (p<0.05). In the ultrastructural analysis, the capillary lumen was closed due to endothelial enlargement, dilatation in the pedicles and hypertrophy in podocytes were found in the 75 mg group. Pedicles in the 50 mg group appeared to be enlarged more than the control group, but the capillary lumen was more open than the 75 mg group.
Conclusion: The results show that low dose mel exposure causes kidney damage with increased doses from the early postnatal period.

References

  • 1. Bolden AL, Rochester JR, Kwiatkowski CF. Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant? Toxicol Lett 2017;280:181-9. [CrossRef] google scholar
  • 2. Dobson RL, Motlagh S, Quijano M, Cambron RT, Baker TR, Pullen AM, et al. Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs. Toxicol Sci 2008;106(1):251- 62. [CrossRef] google scholar
  • 3. Brown CA, Jeong KS, Poppenga RH, Puschner B, Miller DM, Ellis AE, et al. Outbreaks of renal failure associated with melamine and cyanuric acid in dogs and cats in 2004 and 2007. J Vet Diagn Invest 2007;19(5):525-31. [CrossRef] google scholar
  • 4. Dalal RP, Goldfarb DS. Melamine-related kidney stones and renal toxicity. Nat Rev Nephrol 2011;7(5):267-74. [CrossRef] google scholar
  • 5. Zhou W, Jiang Y, Shi H, Dai Q, Liu J, Shen C, et al. The characteristics of immune system changes in children who ingested melamine-contaminated powdered formula in China. Int J Environ Health Res 2010;20(4):289-97. [CrossRef] google scholar
  • 6. Hau AK, Kwan TH, Li PK. Melamine toxicity and the kidney. J Am Soc Nephrol 2009;20(2):245-50. [CrossRef] google scholar
  • 7. Wen JG, Liu XJ, Wang ZM, Li TF, Wahlqvist ML. Melaminecontaminated milk formula and its impact on children. Asia Pac J Clin Nutr 2016;25(4):697-705. google scholar
  • 8. Mast RW, Jeffcoat AR, Sadler BM, Kraska RC, Friedman MA. Metabolism, disposition and excretion of [14C] melamine in male Fischer 344 rats. Food Chem Toxicol 1983;21(6):807- 10. [CrossRef] google scholar
  • 9. WHO. Toxicological and Health Aspects of Melamine and Cyanuric Acid. Report of a WHO Expert Meeting In collaboration with FAO Supported by Health Canada Health Canada, Ottawa, Canada, 1-4 December 2008, page 32. Available from:URL: https://apps.who.int/iris/ bitstream/handle/10665/44106/9789241597951_eng.pdf 1-4 December 2008 google scholar
  • 10. Langman CB, Alon U, Ingelfinger J, Englund M, Saland JM, Somers MJ, et al. A position statement on kidney disease from powdered infant formula-based melamine exposure in Chinese infants. Pediatr Nephrol 2009;24(7):1263-6. [CrossRef] google scholar
  • 11. Park D, Kim TK, Choi YJ, Lee SH, Bae DK, Yang G, et al. Increased nephrotoxicity after combined administration of melamine and cyanuric Acid in rats. Lab Anim Res 2011;27(1):25-8. [CrossRef] google scholar
  • 12. Yasui T, Kobayashi T, Okada A, Hamamoto S, Hirose M, Mizuno K, et al. Long-term follow-up of nephrotoxicity in rats administered both melamine and cyanuric acid. BMC Res Notes 2014;7:87. [CrossRef] google scholar
  • 13. Jacob CC, Reimschuessel R, Von Tungeln LS, Olson GR, Warbritton AR, Hattan DG, et al. Dose-response assessment of nephrotoxicity from a 7-day combined exposure to melamine and cyanuric acid in F344 rats. Toxicol Sci 2011;119 (2):391-7. [CrossRef] google scholar
  • 14. Peerakietkhajorn S, Huipao N, Hiranyachattada S. Effects of melamine and cyanuric acid on renal function and structure in rats. Sains Malaysiana 2019;48(8):1721-8. [CrossRef] google scholar
  • 15. Xie G, Zheng X, Qi X, Cao Y, Chi Y, Su M, et al. Metabonomic evaluation of melamine-induced acute renal toxicity in rats. J Proteome Res 2010;9(1):125-33. [CrossRef] google scholar
  • 16. Gamboa da Costa G, Jacob CC, Von Tungeln LS, Hasbrouck NR, Olson GR, Hattan DG, et al. Dose-response assessment of nephrotoxicity from a twenty-eight-day combinedexposure to melamine and cyanuric acid in F344 rats. Toxicol Appl Pharmacol 2012;262(2):99-106. [CrossRef] google scholar
  • 17. Schnackenberg LK, Sun J, Pence LM, Bhattacharyya S, Gamboa da Costa G, Beger RD. Metabolomics evaluation of hydroxyproline as a potential marker of melamine and cyanuric acid nephrotoxicity in male and female Fischer F344 rats. Food and Chem Toxicol 2012;50(11):3978-83. [CrossRef] google scholar
  • 18. Suchý P, Straková E, Herzig I, Staňa J, Kalusová R, Pospíchalová M. Toxicological risk of melamine and cyanuric acid in food and feed. Interdiscip Toxicol 2009;2(2):55-9. [CrossRef] google scholar
  • 19. Reimschuessel R, Evans ER, Stine CB, Hasbrouck N, Mayer TD, Nochetto C, et al. Renal crystal formation after combined or sequential oral administration of melamine and cyanuric acid. Food Chem Toxicol 2010;48(10):2898- 906. [CrossRef] google scholar
  • 20. Liu CC, Wu CF, Chen BH, Huang SP, Goggins W, Lee HH, et al. Low exposure to melamine increases the risk of urolithiasis in adults. Kidney Int 2011;80(7):746-52. [CrossRef] google scholar
  • 21. Liu C-C, Hsieh T-J, Wu C-F, Lee CH, Tsai YC, Huang TY, et al. Interrelationship of environmental melamine exposure, biomarkers of oxidative stress and early kidney injury. J of Hazard Mater 2020;396:122726. [CrossRef] google scholar
  • 22. Sathyanarayana S, Flynn JT, Messito MJ, Gross R, Whitlock KB, Kannan K, et al. Melamine and cyanuric acid exposure and kidney injury in US children. Environ Res 2019;171:18- 23. [CrossRef] google scholar
  • 23. Sengupta P. The Laboratory Rat: Relating Its Age With Human’s. Int J Prev Med 2013;4(6):624-30. google scholar
  • 24. FDA. Interim Safety and risk assessment of melamine and its analogues in food for humans [a]3 October 2008. Available from: URL: https://wayback.archive-it. org/7993/20170112012209/http://www.fda.gov/Food/ FoodborneIllnessContaminants/ChemicalContaminants/ ucm164522.htm. google scholar
  • 25. Kotyk T, Dey N, Ashour AS, Balas-Timar D, Chakraborty S, Ashour AS, et al. Measurement of glomerulus diameter and Bowman’s space width of renal albino rats. Comput Methods Programs Biomed 2016;126:143-53. [CrossRef] google scholar
  • 26. Márquez MG, Cabrera I, Serrano DJ, Sterin-Speziale N. Cell proliferation and morphometric changes in the rat kidney during postnatal development. Anat Embryol (Berl) 2002;205(5-6):431-40. [CrossRef] google scholar
  • 27. Guo C, He Z, Wen L, Zhu L, Lu Y, Deng S, et al. Cytoprotective effect of trolox against oxidative damage and apoptosis in the NRK-52e cells induced by melamine. Cell Biol Int 2012;36(2):183-8. [CrossRef] google scholar
  • 28. Kuo FC, Tseng YT, Wu SR, Wu MT, Lo YC. Mel activates NFkappaB/COX-2/PGE2 pathway and increases NADPH oxidase-dependent ROS production in macrophages and human embryonic kidney cells. Toxicol In Vitro 2013;27(6):1603-11. [CrossRef] google scholar
  • 29. Lee IC, Ko JW, Park SH, Shin IS, Moon C, Kim SH, et al. Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling. Food Chem Toxicol 2016;96:254- 62. [CrossRef] google scholar
  • 30. Erisgin Z, Usta M. Does melamine exposure during infancy cause rhabdomyolysis? Biotech Histochem 2021;96(2):102- 10. [CrossRef] google scholar

ERKEN POSTNATAL DÖNEMDEN İTİBAREN MELAMİN MARUZİYETİ NEFROTOKSİSİTEYE NEDEN OLUR: BİR HİSTOPATOLOJİK VE ULTRASÜTRÜKTÜREL ÇALIŞMA

Year 2022, Volume: 85 Issue: 3, 433 - 439, 06.07.2022
https://doi.org/10.26650/IUITFD.1074354

Abstract

Amaç: İllegal olarak mamalara yalancı yüksek pozitif protein içeriği için eklenen melamin (mel), bebeklerde kristal oluşumuna bağlı akut böbrek yetmezliğine neden olmuştur. Bu çalışmada süt kesme döneminden (ek besin dönemi) itibaren kronik düşük doz mel maruziyetinin nefrotoksik etkilerinin araştırılması amaçlandı.
Gereç ve Yöntem: Süt kesim dönemindeki (21 günlük) 18 dişi sıçan üç gruba bölündü. Kontrol grubuna 0.1 ml serum fizyolojik oral gavajla (p.o) verildi. İkinci gruba 50 mg/kg mel, üçüncü gruba 75 mg/kg mel 0.1 ml serum fizyolojik ile çözülerek yirmi bir gün p.o. verildi. Deney sonunda hayvanlar sakrifiye edildi ve böbrek dokularında histopatolojik, morfometrik ve ultrasütrüktürel analiz yapıldı.
Bulgular: Her iki mel grubunda tubulointerstisyel alanda inflamatuar hücre infiltrasyonu vardı ve kristal oluşumu gözlenmedi. Yetmiş beş mg mel grubunda glomerüler ve tübüler epitel hasarı ve Bowman boşluğunda önemli artışlar gözlendi (p<0.05). Yetmiş beş mg grubunda ultrasütrüktürel analizlerinde endotel genişlemesi nedeniyle kapiller lümenin kapandığı, pedisellerde dilatasyon ve podositlerde hipertrofi saptandı. Elli mg grubundaki pediseller kontrol grubuna göre daha fazla genişlemiş gibi görünüyordu. Elli mg grubunda, kapiller lümen 75 mg grubuna göre daha açıktı.
Tartışma: Sonuç olarak, erken postanal dönemden itibaren düşük doz mel maruziyeti artan dozlarda böbrek hasarına neden olmaktadır.

References

  • 1. Bolden AL, Rochester JR, Kwiatkowski CF. Melamine, beyond the kidney: A ubiquitous endocrine disruptor and neurotoxicant? Toxicol Lett 2017;280:181-9. [CrossRef] google scholar
  • 2. Dobson RL, Motlagh S, Quijano M, Cambron RT, Baker TR, Pullen AM, et al. Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs. Toxicol Sci 2008;106(1):251- 62. [CrossRef] google scholar
  • 3. Brown CA, Jeong KS, Poppenga RH, Puschner B, Miller DM, Ellis AE, et al. Outbreaks of renal failure associated with melamine and cyanuric acid in dogs and cats in 2004 and 2007. J Vet Diagn Invest 2007;19(5):525-31. [CrossRef] google scholar
  • 4. Dalal RP, Goldfarb DS. Melamine-related kidney stones and renal toxicity. Nat Rev Nephrol 2011;7(5):267-74. [CrossRef] google scholar
  • 5. Zhou W, Jiang Y, Shi H, Dai Q, Liu J, Shen C, et al. The characteristics of immune system changes in children who ingested melamine-contaminated powdered formula in China. Int J Environ Health Res 2010;20(4):289-97. [CrossRef] google scholar
  • 6. Hau AK, Kwan TH, Li PK. Melamine toxicity and the kidney. J Am Soc Nephrol 2009;20(2):245-50. [CrossRef] google scholar
  • 7. Wen JG, Liu XJ, Wang ZM, Li TF, Wahlqvist ML. Melaminecontaminated milk formula and its impact on children. Asia Pac J Clin Nutr 2016;25(4):697-705. google scholar
  • 8. Mast RW, Jeffcoat AR, Sadler BM, Kraska RC, Friedman MA. Metabolism, disposition and excretion of [14C] melamine in male Fischer 344 rats. Food Chem Toxicol 1983;21(6):807- 10. [CrossRef] google scholar
  • 9. WHO. Toxicological and Health Aspects of Melamine and Cyanuric Acid. Report of a WHO Expert Meeting In collaboration with FAO Supported by Health Canada Health Canada, Ottawa, Canada, 1-4 December 2008, page 32. Available from:URL: https://apps.who.int/iris/ bitstream/handle/10665/44106/9789241597951_eng.pdf 1-4 December 2008 google scholar
  • 10. Langman CB, Alon U, Ingelfinger J, Englund M, Saland JM, Somers MJ, et al. A position statement on kidney disease from powdered infant formula-based melamine exposure in Chinese infants. Pediatr Nephrol 2009;24(7):1263-6. [CrossRef] google scholar
  • 11. Park D, Kim TK, Choi YJ, Lee SH, Bae DK, Yang G, et al. Increased nephrotoxicity after combined administration of melamine and cyanuric Acid in rats. Lab Anim Res 2011;27(1):25-8. [CrossRef] google scholar
  • 12. Yasui T, Kobayashi T, Okada A, Hamamoto S, Hirose M, Mizuno K, et al. Long-term follow-up of nephrotoxicity in rats administered both melamine and cyanuric acid. BMC Res Notes 2014;7:87. [CrossRef] google scholar
  • 13. Jacob CC, Reimschuessel R, Von Tungeln LS, Olson GR, Warbritton AR, Hattan DG, et al. Dose-response assessment of nephrotoxicity from a 7-day combined exposure to melamine and cyanuric acid in F344 rats. Toxicol Sci 2011;119 (2):391-7. [CrossRef] google scholar
  • 14. Peerakietkhajorn S, Huipao N, Hiranyachattada S. Effects of melamine and cyanuric acid on renal function and structure in rats. Sains Malaysiana 2019;48(8):1721-8. [CrossRef] google scholar
  • 15. Xie G, Zheng X, Qi X, Cao Y, Chi Y, Su M, et al. Metabonomic evaluation of melamine-induced acute renal toxicity in rats. J Proteome Res 2010;9(1):125-33. [CrossRef] google scholar
  • 16. Gamboa da Costa G, Jacob CC, Von Tungeln LS, Hasbrouck NR, Olson GR, Hattan DG, et al. Dose-response assessment of nephrotoxicity from a twenty-eight-day combinedexposure to melamine and cyanuric acid in F344 rats. Toxicol Appl Pharmacol 2012;262(2):99-106. [CrossRef] google scholar
  • 17. Schnackenberg LK, Sun J, Pence LM, Bhattacharyya S, Gamboa da Costa G, Beger RD. Metabolomics evaluation of hydroxyproline as a potential marker of melamine and cyanuric acid nephrotoxicity in male and female Fischer F344 rats. Food and Chem Toxicol 2012;50(11):3978-83. [CrossRef] google scholar
  • 18. Suchý P, Straková E, Herzig I, Staňa J, Kalusová R, Pospíchalová M. Toxicological risk of melamine and cyanuric acid in food and feed. Interdiscip Toxicol 2009;2(2):55-9. [CrossRef] google scholar
  • 19. Reimschuessel R, Evans ER, Stine CB, Hasbrouck N, Mayer TD, Nochetto C, et al. Renal crystal formation after combined or sequential oral administration of melamine and cyanuric acid. Food Chem Toxicol 2010;48(10):2898- 906. [CrossRef] google scholar
  • 20. Liu CC, Wu CF, Chen BH, Huang SP, Goggins W, Lee HH, et al. Low exposure to melamine increases the risk of urolithiasis in adults. Kidney Int 2011;80(7):746-52. [CrossRef] google scholar
  • 21. Liu C-C, Hsieh T-J, Wu C-F, Lee CH, Tsai YC, Huang TY, et al. Interrelationship of environmental melamine exposure, biomarkers of oxidative stress and early kidney injury. J of Hazard Mater 2020;396:122726. [CrossRef] google scholar
  • 22. Sathyanarayana S, Flynn JT, Messito MJ, Gross R, Whitlock KB, Kannan K, et al. Melamine and cyanuric acid exposure and kidney injury in US children. Environ Res 2019;171:18- 23. [CrossRef] google scholar
  • 23. Sengupta P. The Laboratory Rat: Relating Its Age With Human’s. Int J Prev Med 2013;4(6):624-30. google scholar
  • 24. FDA. Interim Safety and risk assessment of melamine and its analogues in food for humans [a]3 October 2008. Available from: URL: https://wayback.archive-it. org/7993/20170112012209/http://www.fda.gov/Food/ FoodborneIllnessContaminants/ChemicalContaminants/ ucm164522.htm. google scholar
  • 25. Kotyk T, Dey N, Ashour AS, Balas-Timar D, Chakraborty S, Ashour AS, et al. Measurement of glomerulus diameter and Bowman’s space width of renal albino rats. Comput Methods Programs Biomed 2016;126:143-53. [CrossRef] google scholar
  • 26. Márquez MG, Cabrera I, Serrano DJ, Sterin-Speziale N. Cell proliferation and morphometric changes in the rat kidney during postnatal development. Anat Embryol (Berl) 2002;205(5-6):431-40. [CrossRef] google scholar
  • 27. Guo C, He Z, Wen L, Zhu L, Lu Y, Deng S, et al. Cytoprotective effect of trolox against oxidative damage and apoptosis in the NRK-52e cells induced by melamine. Cell Biol Int 2012;36(2):183-8. [CrossRef] google scholar
  • 28. Kuo FC, Tseng YT, Wu SR, Wu MT, Lo YC. Mel activates NFkappaB/COX-2/PGE2 pathway and increases NADPH oxidase-dependent ROS production in macrophages and human embryonic kidney cells. Toxicol In Vitro 2013;27(6):1603-11. [CrossRef] google scholar
  • 29. Lee IC, Ko JW, Park SH, Shin IS, Moon C, Kim SH, et al. Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling. Food Chem Toxicol 2016;96:254- 62. [CrossRef] google scholar
  • 30. Erisgin Z, Usta M. Does melamine exposure during infancy cause rhabdomyolysis? Biotech Histochem 2021;96(2):102- 10. [CrossRef] google scholar
There are 30 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section RESEARCH
Authors

Züleyha Erişgin 0000-0003-3523-6542

Hasan Serdar Mutlu This is me 0000-0002-4267-9619

Publication Date July 6, 2022
Submission Date February 16, 2022
Published in Issue Year 2022 Volume: 85 Issue: 3

Cite

APA Erişgin, Z., & Mutlu, H. S. (2022). EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY. Journal of Istanbul Faculty of Medicine, 85(3), 433-439. https://doi.org/10.26650/IUITFD.1074354
AMA Erişgin Z, Mutlu HS. EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY. İst Tıp Fak Derg. July 2022;85(3):433-439. doi:10.26650/IUITFD.1074354
Chicago Erişgin, Züleyha, and Hasan Serdar Mutlu. “EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY”. Journal of Istanbul Faculty of Medicine 85, no. 3 (July 2022): 433-39. https://doi.org/10.26650/IUITFD.1074354.
EndNote Erişgin Z, Mutlu HS (July 1, 2022) EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY. Journal of Istanbul Faculty of Medicine 85 3 433–439.
IEEE Z. Erişgin and H. S. Mutlu, “EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY”, İst Tıp Fak Derg, vol. 85, no. 3, pp. 433–439, 2022, doi: 10.26650/IUITFD.1074354.
ISNAD Erişgin, Züleyha - Mutlu, Hasan Serdar. “EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY”. Journal of Istanbul Faculty of Medicine 85/3 (July 2022), 433-439. https://doi.org/10.26650/IUITFD.1074354.
JAMA Erişgin Z, Mutlu HS. EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY. İst Tıp Fak Derg. 2022;85:433–439.
MLA Erişgin, Züleyha and Hasan Serdar Mutlu. “EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY”. Journal of Istanbul Faculty of Medicine, vol. 85, no. 3, 2022, pp. 433-9, doi:10.26650/IUITFD.1074354.
Vancouver Erişgin Z, Mutlu HS. EXPOSURE TO MELAMINE FROM THE EARLY POSTNATAL PERIOD CAUSES NEPROTOXICITY: A HISTOPATHOLOGIC AND ULTRASTRUCTURAL STUDY. İst Tıp Fak Derg. 2022;85(3):433-9.

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