Investigation of the Effects of Formaldehyde Exposure on BDNF and FGF23 Levels in Kidney Tissues of Rats

Abstract

Aim: Formaldehyde (FA) is a highly toxic chemical agent that can easily turn into gas at room temperature. It has a wide range of uses. Anatomists, pathologists, and histologists are frequently exposed to FA due to their areas of practice. Brain-derived neurotrophic factor is a protein secreted from the central nervous system and peripheral tissues that support the differentiation and growth of newly formed nerve cells and synapses. It is proven to be expressed in renal glomeruli. FGF23 is a bone-derived hormone that regulates phosphate and calcium homeostasis. It is a critical component of the abnormal mineral metabolism that complicates chronic kidney disease. This study investigates the effect of FA exposure on 3BDNF and FGF23 levels in rat kidney tissue. Material and Methods: The study included 14 male Spraque- Dawley rats (7 animals in each group) aged between 8 and 10 weeks. During the experiment, the rats in the control group were exposed to natural atmospheric air in a glass bell jar. The rats in the FA group inhaled 10 ppm 8 h/day FA in a glass bell jar 5 days a week (excluding Saturdays and Sundays) for 4 weeks. At the end of the experiment, the rats were decapitated, and their kidneys were removed. Kidney tissues were homogenized and tested using the ELISA method. Results: It was observed that BDNF levels significantly decreased and FGF23 levels significantly increased in the kidney tissues of FA-exposed rats compared to the control group. Conclusions: This study first demonstrated the effect of exposure to FA on FGF23 and BDNF levels in rat kidney tissue. This study will contribute to future research on oxidants that increase FGF23 and BDNF expression or antioxidants that target their reduction. Accordingly, we consider it will also contribute to public health.

Keywords

• formaldehyde exposure
• FGF23
• BDNF
• kidney; rat

References

1. 1. Kim CW, Song JS, Ahn YS, Park SH, Park JW, Noh JH, et al. Occupational asthma due to formaldehyde. Yonsei Med J. 2001;42(4):440–5.
2. 2. Zhou DX, Qiu SD, Zhang J, Tian H, Wang HX. The protective effect of vitamin E against oxidative damage caused by formaldehyde in the testes of adult rats. Asian J. Androl. 2006;8:584–8.
3. 3. Nielsen GD, Larsen ST, Wolkoff P. Recent trend in risk assessment of formaldehyde exposures from indoor air. Arch Toxicol. 2013;87(1):73–98.
4. 4. Bakar E, Ulucam E, Cerkezkayabekir A. Investigation of the protective effects of proanthocyanidin and vitamin E against the toxic effect caused by formaldehyde on the liver tissue. Env Toxicol. 2015;30:1406–15.
5. 5. Yamada K, Nabeshima T. Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci. 2003;91(4):267–70.
6. 6. Lommatzsch M, Niewerth A, Klotz J, Schulte-Herbrüggen O, Zingler C, Schuff-Werner P, et al. Platelet and plasma BDNF in lower respiratory tract infections of the adult. Respir Med. 2007;101(7):1493–9.
7. 7. Endlich N, Lange T, Kuhn J, Klemm P, Kotb AM, Siegerist F, et al. BDNF. mRNA expression in urine cells of patients with chronic kidney disease and its role in kidney function. J Cell Mol Med. 2018;22(11):5265–77.
8. 8. Tao YS, Piao SG, Jin YS, Jin JZ, Zheng HL, Zhao HY, et al. Expression of brain-derived neurotrophic factor in kidneys from normal and cyclosporine-treated rats. BMC Nephrol. 2018;19(1):63.

9. 9. Cırrık S, Hacioglu G, Ayyıldız SN, Tezcan B, Abidin İ, Aydın- Abidin S, et al. Renal response to tunicamycin-induced endoplasmic reticulum stress in BDNF heterozygous mice. Adv Clin Exp Med. 2019;28(9):1161–70.
10. 10. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol. 2013;75:503–33.
11. 11. Chen G, Liu Y, Goetz R, Fu L, Jayaraman S, Hu MC, et al. α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling. Nature. 2018;553(7689):461–6.
12. 12. Wolf M. Mineral (Mal) Adaptation to Kidney Disease-Young Investigator Award Address: American Society of Nephrology Kidney Week 2014. Clin J Am Soc Nephrol. 2015;10(10):1875–85.
13. 13. ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000;26(3):345–8.
14. 14. Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol. 2005;16(7):2205–15.
15. 15. Shigematsu T, Kazama JJ, Yamashita T, Fukumoto S, Hosoya T, Gejyo F, et al. Possible involvement of circulatingfibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004;44(2):250–6.
16. 16. Aydin S, Ogeturk M, Kuloglu T, Kavakli A, Aydin S. Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation. Peptides. 2015;64:14–23.
17. 17. Akkoc RF, Ogeturk M, Aydin S, Kuloglu T, Aydin S. Effects of carnosine on apoptosis, transient receptor potential melastatin 2, and betatrophin in rats exposed to formaldehyde. Biotech Histochem. 2021;96(3):223–9.
18. 18. Afsar B, Afsar RE. Brain-derived neurotrophic factor (BDNF): a multifaceted marker in chronic kidney disease. Clin Exp Nephrol. 2022;26(12):1149–59.
19. 19. Ge S, Yan B, Huang J, Chen Y, Chen M, Yang X, et al. Diisodecyl phthalate aggravates the formaldehyde-exposure-induced learning and memory impairment in mice. Food Chem Toxicol. 2019;126:152–61.
20. 20. Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121(11):4393–08.
21. 21. Wolf M, White KE. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Curr Opin Nephrol Hypertens. 2014;23(4):411–9.
22. 22. Portale AA, Wolf M, Jüppner H, Messinger S, Kumar J, Wesseling-Perry K, et al. Disordered FGF23 and mineral metabolism in children with CKD. Clin J Am Soc Nephrol. 2014;9(2):344–53.