open access

Ahead of Print
Original article
Submitted: 2021-02-19
Accepted: 2021-05-06
Published online: 2021-05-17
Get Citation

KEAP1/Nrf2 pathway in sodium fluoride-induced cardiac toxicity and the prophylactic role of vitamin C versus platelet-rich plasma

H. Labib1, A. M. Badr2, M. Abdelgwad2, T. I. Abd el-galil1
DOI: 10.5603/FM.a2021.0053
·
Pubmed: 34018173
Affiliations
  1. Department of Anatomy and Embryology, Cairo University, Cairo, Egypt
  2. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, KasrAlainy, Cairo University, Cairo, Egypt

open access

Ahead of Print
ORIGINAL ARTICLES
Submitted: 2021-02-19
Accepted: 2021-05-06
Published online: 2021-05-17

Abstract

The present study was conducted to investigate the role of vitamin C versus platelet-rich plasma against sodium fluoride (NaF)-induced cardiotoxicity and cell death in rats’ myocardium. Previous studies suggest that NaF decreased cellular viability and intracellular antioxidant power. The present study revealed that NaF administration caused histological alterations in the cardiac muscle and increased the accumulation of intracellular reactive oxygen species, the expression of iNOS and PCNA as well as collagen deposition in cardiac tissue. As supported by colorimetric analysis, an elevation in MDA level and a decrease in both SOD and TrX levels were seen, whereas molecular analysis revealed a decrease in Keap1 and an increase in Nrf2 and HO-1 gene expression. Pretreatment with vitamin C and PRP prior to NaF administration significantly improved the altered parameters and enhanced the cellular antioxidant capability of myocardium resulting in protection of cardiac muscle from NaF-induced cytotoxicity and apoptotic cell death. The cyto-protective activity of PRP was found to be comparable to that of the known antioxidant, vitamin C.

Abstract

The present study was conducted to investigate the role of vitamin C versus platelet-rich plasma against sodium fluoride (NaF)-induced cardiotoxicity and cell death in rats’ myocardium. Previous studies suggest that NaF decreased cellular viability and intracellular antioxidant power. The present study revealed that NaF administration caused histological alterations in the cardiac muscle and increased the accumulation of intracellular reactive oxygen species, the expression of iNOS and PCNA as well as collagen deposition in cardiac tissue. As supported by colorimetric analysis, an elevation in MDA level and a decrease in both SOD and TrX levels were seen, whereas molecular analysis revealed a decrease in Keap1 and an increase in Nrf2 and HO-1 gene expression. Pretreatment with vitamin C and PRP prior to NaF administration significantly improved the altered parameters and enhanced the cellular antioxidant capability of myocardium resulting in protection of cardiac muscle from NaF-induced cytotoxicity and apoptotic cell death. The cyto-protective activity of PRP was found to be comparable to that of the known antioxidant, vitamin C.

Get Citation

Keywords

sodium fluoride, vitamin C, PRP, Keap-1, Nrf2, Trx-1

About this article
Title

KEAP1/Nrf2 pathway in sodium fluoride-induced cardiac toxicity and the prophylactic role of vitamin C versus platelet-rich plasma

Journal

Folia Morphologica

Issue

Ahead of Print

Article type

Original article

Published online

2021-05-17

Page views

742

Article views/downloads

677

DOI

10.5603/FM.a2021.0053

Pubmed

34018173

Keywords

sodium fluoride
vitamin C
PRP
Keap-1
Nrf2
Trx-1

Authors

H. Labib
A. M. Badr
M. Abdelgwad
T. I. Abd el-galil

References (52)
  1. Ago T, Yeh I, Yamamoto M, et al. Thioredoxin1 upregulates mitochondrial proteins related to oxidative phosphorylation and TCA cycle in the heart. Antioxid Redox Signal. 2006; 8(9-10): 1635–1650.
  2. Al Shahat AA, Naggar A. Possible protective role of calcium against fluoride induced cardio toxicities in adult male albino rats. J Am Sci. 2013; 9(4): 1–5.
  3. Araujo JA, Zhang M, Yin F. Heme oxygenase-1, oxidation, inflammation, and atherosclerosis. Front Pharmacol. 2012; 3: 119.
  4. Hammett-Stabler CA. Disposition of toxic drugs and chemicals in man. RC Baselt. Foster City, CA: Chemical Toxicology Institute. 1999; 90.
  5. Basha MP, Sujitha NS. Chronic fluoride toxicity and myocardial damage: antioxidant offered protection in second generation rats. Toxicol Int. 2011; 18(2): 99–104.
  6. Bielecki T, Dohan Ehrenfest DM, Everts PA, et al. The role of leukocytes from L-PRP/L-PRF in wound healing and immune defense: new perspectives. Curr Pharm Biotechnol. 2012; 13(7): 1153–1162.
  7. Chen HN, Wang DJ, Ren MY, et al. TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-кB pathway. Mol Biol Rep. 2012; 39(8): 8231–8241.
  8. Chinoy NJ. Effects of fluoride on physiology of animals and human beings. Indian J Environ Toxicol. 1991; 1(1): 17–32.
  9. Cicek E, Aydin G, Akdogan M, et al. Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats. Hum Exp Toxicol. 2005; 24(2): 79–87.
  10. Delker SL, Xue F, Li H, et al. Role of zinc in isoform-selective inhibitor binding to neuronal nitric oxide synthase . Biochemistry. 2010; 49(51): 10803–10810.
  11. Erdal S, Buchanan SN. A quantitative look at fluorosis, fluoride exposure, and intake in children using a health risk assessment approach. Environ Health Perspect. 2005; 113(1): 111–117.
  12. Fabiyi-Edebor TD. Vitamin C ameliorated cardiac autonomic neuropathy in type 2 diabetic rats. World J Diabetes. 2020; 11(3): 52–65.
  13. Fuse Y, Kobayashi M. Conservation of the Keap1-Nrf2 System: An Evolutionary Journey through Stressful Space and Time. Molecules. 2017; 22(3).
  14. Ghosh J, Das J, Manna P, et al. Cytoprotective effect of arjunolic acid in response to sodium fluoride mediated oxidative stress and cell death via necrotic pathway. Toxicol In Vitro. 2008; 22(8): 1918–1926.
  15. Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012; 367(12): 1098–1107.
  16. Goshman LM. Clinical toxicology of commercial products, By RE Gosselin, RP Smith, and HC Hodge. Williams and Wilkins, Baltimore 1984.
  17. Gupta AR, Dey S, Saini M, et al. Protective effect ofTamarindus indicafruit pulp extract on collagen content and oxidative stress induced by sodium fluoride in the liver and kidney of rats. Toxicological & Environmental Chemistry. 2014; 95(9): 1611–1623.
  18. Gupta AR, Dey S, Swarup D, et al. Effects of excessive fluoride ingestion on collagen protein and expression of type I collagen gene in skeletal muscles of rats. Fluoride. 2013; 46(3): 149–55.
  19. Hargrave BY. Autologous platelet rich plasma (platelet gel): an appropriate intervention for salvaging cardiac myocytes under oxidative stress after myocardial infarction. Anatomy & Physiology. 2013; 04(01).
  20. He WW, Wang WY, Deng J, et al. L-NMMA and1400W, inhibitor of iNOS, attenuate the induction of iNOS and NO in primary rabbit costal chondrocytes by fluoride. Fluoride. 2020; 53(2): 220–238.
  21. Itoh K, Ishii T, Wakabayashi N, et al. Regulatory mechanisms of cellular response to oxidative stress. Free Radic Res. 1999; 31(4): 319–324.
  22. Jakobs P, Serbulea V, Leitinger N, et al. Nuclear factor (erythroid-derived 2)-like 2 and thioredoxin-1 in atherosclerosis and ischemia/reperfusion injury in the heart. Antioxid Redox Signal. 2017; 26(12): 630–644.
  23. Kojo S. Vitamin C: basic metabolism and its function as an index of oxidative stress. Curr Med Chem. 2004; 11(8): 1041–1064.
  24. Lawal AO, Lawal AF, Ologundudu A, et al. Antioxidant effects of heated garlic juice on cadmium-induced liver damage in rats as compared to ascorbic acid. J Toxicol Sci. 2011; 36(5): 549–557.
  25. Liu AJ, Li B, Yang M, et al. Sirtuin 1 mediates hydrogen sulfide-induced cytoprotection effects in neonatal mouse cardiomyocytes. Chinese Med J. 2017; 130(19): 2346.
  26. Luo Q, Guo H, Kuang P, et al. Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice. Cell Physiol Biochem. 2018; 51(5): 2421–2433.
  27. Lusigi EM. Quality Assessment of Rain and Storm Water Runoff for Nairobi City Industrial and Sub-Urban Areas (Doctoral dissertation), University of Nairobi, 2017.
  28. Martins RP, Hartmann DD, de Moraes JP, et al. Platelet-rich plasma reduces the oxidative damage determined by a skeletal muscle contusion in rats. Platelets. 2016; 27(8): 784–790.
  29. McDonagh MS, Whiting PF, Wilson PM, et al. Systematic review of water fluoridation. BMJ. 2000; 321(7265): 855–859.
  30. Moi P, Chan K, Asunis I, et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A. 1994; 91(21): 9926–9930.
  31. Moraes VY, Lenza M, Tamaoki MJ, et al. Platelet-rich therapies for musculoskeletal soft tissue injuries. Cochrane Database Syst Rev. 2014(4): CD010071.
  32. Mostafavi-Pour Z, Ramezani F, Keshavarzi F, et al. The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production in breast cancer cells. Oncol Lett. 2017; 13(3): 1965–1973.
  33. Nair V, O'Neil C, Wang P. Malondialdehyde. Encyclopedia of Reagents for Organic Synthesis. 2008.
  34. Ngoc TD, Son YO, Lim SS, et al. Sodium fluoride induces apoptosis in mouse embryonic stem cells through ROS-dependent and caspase- and JNK-mediated pathways. Toxicol Appl Pharmacol. 2012; 259(3): 329–337.
  35. Oyagbemi AA, Omobowale TO, Asenuga ER, et al. Sodium fluoride induces hypertension and cardiac complications through generation of reactive oxygen species and activation of nuclear factor kappa beta. Environ Toxicol. 2017; 32(4): 1089–1101.
  36. Padayatty SJ, Katz A, Wang Y, et al. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003; 22(1): 18–35.
  37. Peng W, Xu S, Zhang J, et al. Vitamin c attenuates sodium fluoride-induced mitochondrial oxidative stress and apoptosis via Sirt1-SOD2 pathway in F9 cells. Biol Trace Elem Res. 2019; 191(1): 189–198.
  38. Pi H, Xu S, Reiter RJ, et al. SIRT3-SOD2-mROS-dependent autophagy in cadmium-induced hepatotoxicity and salvage by melatonin. Autophagy. 2015; 11(7): 1037–1051.
  39. Piantadosi CA, Carraway MS, Babiker A, et al. Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res. 2008; 103(11): 1232–1240.
  40. Popovic LM, Mitic NR, Miric D, et al. Influence of vitamin C supplementation on oxidative stress and neutrophil inflammatory response in acute and regular exercise. Oxid Med Cell Longev. 2015; 2015: 295497.
  41. Saif-Elnasr M, Abdel Fattah SM, Swailam HM. Treatment of hepatotoxicity induced by γ-radiation using platelet-rich plasma and/or low molecular weight chitosan in experimental rats. Int J Radiat Biol. 2019; 95(11): 1517–1528.
  42. Shenoy PS, Sen U, Kapoor S, et al. Sodium fluoride induced skeletal muscle changes: Degradation of proteins and signaling mechanism. Environ Pollut. 2019; 244: 534–548.
  43. Smith RE, Tran K, Smith CC, et al. The Role of the Nrf2/ARE antioxidant system in preventing cardiovascular diseases. Diseases. 2016; 4(4).
  44. Spartalis E, Tomos P, Moris D, et al. Role of platelet-rich plasma in ischemic heart disease: An update on the latest evidence. World J Cardiol. 2015; 7(10): 665–670.
  45. Viswanathan G, Gopalakrishnan S, Siva Ilango S. Assessment of water contribution on total fluoride intake of various age groups of people in fluoride endemic and non-endemic areas of Dindigul District, Tamil Nadu, South India. Water Res. 2010; 44(20): 6186–6200.
  46. Wang D, Shi JQ, Liu FX. Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma. World J Gastroenterol. 1997; 3(2): 101–103.
  47. Wakabayashi N, Itoh K, Wakabayashi J, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet. 2003; 35(3): 238–245.
  48. Xu S, Gao Y, Zhang Q, et al. SIRT1/3 activation by resveratrol attenuates acute kidney injury in a septic rat model. Oxid Med Cell Longev. 2016; 2016: 7296092.
  49. Yildirim S, Ekin S, Huyut Z, et al. Effect of chronic exposure to sodium fluoride and 7, 12-dimethylbenz [a] anthracene on some blood parameters and hepatic, renal, and cardiac histopathology in rats. Fluoride. 2018; 51(3): 278–290.
  50. Yin B, Di L, Tang S, et al. Vitamin CNa enhances the antioxidant ability of chicken myocardium cells and induces heat shock proteins to relieve heat stress injury. Res Vet Sci. 2020; 133: 124–130.
  51. Zaki SM, Algaleel WaA, Imam RA, et al. Mesenchymal stem cells pretreated with platelet-rich plasma modulate doxorubicin-induced cardiotoxicity. Hum Exp Toxicol. 2019; 38(7): 857–874.
  52. Zhao WP, Wang HW, Liu J, et al. Positive PCNA and Ki-67 expression in the testis correlates with spermatogenesis dysfunction in fluoride-treated rats. Biol Trace Elem Res. 2018; 186(2): 489–497.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By  "Via Medica sp. z o.o." sp.k., Świętokrzyska 73, 80–180 Gdańsk, Poland

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl