Dental and Medical Problems

Dent Med Probl
Index Copernicus (ICV 2020) – 128.41
MEiN – 70 pts
CiteScore (2021) – 2.0
JCI – 0.5
Average rejection rate (2021) – 81.35%
ISSN 1644-387X (print)
ISSN 2300-9020 (online)
Periodicity – quarterly

Download PDF

Dental and Medical Problems

2018, vol. 55, nr 1, January-March, p. 11–16

doi: 10.17219/dmp/81592

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Creative Commons BY-NC-ND 3.0 Open Access

Alveolar process changes associated with administration of nucleos(t)ide analogue (sofosbuvir) in rat model

Zmiany wyrostka zębodołowego związane z zastosowaniem analogu nukleozydów (sofosbuwiru) w badaniu u szczurów

Dina Badawy Elsayed Farag1,A,B,C,D,F, Dalia Abdel-hameed El-Baz1,A,C,D,F, Zeinab Amin Salem1,A,B,E,F

1 Department of Oral Biology, Faculty of Dentistry, Cairo University, Cairo, Egypt

Abstract

Background. Sofosbuvir is a nucleotide compound that has proved to be among the most potent orally available antiviral treatments. Infrequent but serious adverse events have been reported with the use of oral nucleos(t)ide analogues.
Objectives. Investigating sofosbuvir-induced alterations in the rat mandibular alveolar process.
Material and Methods. In the study, 30 adult male albino rats were used and divided randomly into following groups: group 1, group 2 and group 3 (10 rats per group). Group 1 served as a control, group 2 received sofosbuvir through oral gavage at a dose of 40 mg/kg/day for 6 weeks, and group 3 was similar to group 2 but received sofosbuvir for 12 weeks. The animals were sacrificed at the end of the experiment. The mandibles were dissected and examined histologically as well as by scanning electron microscope (SEM) and energy dispersive X-ray unit (EDX).
Results. Histologically, group 1 showed normal alveolar process. In group 2, histopathological changes occurred as bone trabeculae demonstrated obvious Howship’s lacuna of osteoclasts. In group 3, bone trabeculae exhibited multiple degenerated areas as well as apparent vacuolization. Scanning electron microscopic examination revealed smooth alveolar bone architecture in group 1. On the other hand, groups 2 and 3 demonstrated irregular bone architecture with formation of multiple pores. EDX analysis demonstrated the highest calcium concentration in the control group, while the lowest was found in group 3. Statistical analysis of the EDX results revealed a statistically significant difference among the studied groups as the p-value was <0.01.
Conclusion. It has been concluded that sofosbuvir induced apparent alterations in the rats’ alveolar bone. This effect was exaggerated in a longer period of drug administration. The sofosbuvir-induced alterations might be attributed mainly to mitochondrial toxicity. The effect had been clearly shown histologically and morphologically as well as in bone mineral (calcium) content.

Key words

hepatitis C virus, alveolar bone, sofosbuvir, nucleos(t)ide analogues, scanning microscopy

Słowa kluczowe

wirus zapalenia wątroby typu C, kość wyrostka zębodołowego, sofosbuwir, analogi nukleozydów, mikroskopia skaningowa

References (30)

  1. Gerber L, Welzel TM, Zeuzem S. New therapeutic strategies in HCV polymerase inhibitors. Liver Int. 2013;33:85–92.
  2. De Clercq E. A 40 year journey in search of selective antiviral chemotherapy. Annu Rev Pharmacol Toxicol. 2011;51:1–24.
  3. Galmarini CM, Mackey JR, Dumontet C. Nucleoside analogues: Mechanisms of drug resistance and reversal strategies. Leukemia. 2001;15:875–890.
  4. Lam AM, Espiritu C, Bansal S, et al. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob Agents Chemother. 2012;56:3359–3368.
  5. Johnson AA, Ray AS, Hanes J, et al. Toxicity of antiviral nucleoside analogs and the human mitochondrial DNA polymerase. J Biol Chem. 2001;276:40847–40857.
  6. Mc Quaid T, Savini C, Seyedkazemi S. Sofosbuvir, a significant paradigm change in HCV treatment. J Clin Transl Hepatol. 2015;3:27–35.
  7. Shin JW, Seol IC, Son CG. Interpretation of animal dose and human equivalent dose for drug development. J Korean Oriental Med. 2010;31:1–7.
  8. Sofia MJ. Nucleotide prodrugs for HCV therapy. Antivir Chem Chemother. 2011;22:23–49.
  9. Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61:45–57.
  10. Le Pogam S, Seshaadri A, Kosaka A, et al. Existence of hepatitis C virus NS5B variants naturally resistant to non-nucleoside, but not to nucleoside, polymerase inhibitors among untreated patients. J Antimicrob Chemother. 2008;61:1205–1216.
  11. Stedman C. Sofosbuvir, a NS5B polymerase inhibitor in the treatment of hepatitis C: A review of its clinical potential. Therap Adv Gatroenterol. 2014;7:131–140.
  12. Bhatia HK, Singh H, Grewal N, Natt NK. Sofosbuvir: A novel treatment option for chronic hepatitis C infection. J Pharmacol Pharmacother. 2014;5:278–284.
  13. Gentile I, Borgia F, Buonomo AR, Castaldo G, Borgia G. A novel promising therapeutic option against hepatitis C virus: An oral nucleotide NS5B polymerase inhibitor sofosbuvir. Curr Med Chem. 2013;20:3733–3742.
  14. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–1887.
  15. Zeuzem S, Dusheiko GM, Salupere R, et al. Sofosbuvir + ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE trial [abstract 1085]. In: Program and abstracts of the 64th Annual Meeting of the American Association for the Study of Liver Diseases. Washington, DC: 2013.
  16. Neve A, Corrado A, Cantatore FP. Osteocytes: Central conductors of bone biology in normal and pathological conditions. Acta Physiol (Oxf). 2012;204:317–330.
  17. Shapiro R, Heaney RP. Co-dependence of calcium and phosphorus for growth and bone development under conditions of varying deficiency. Bone. 2003;32:532–540.
  18. Coats AM, Zioupos P, Aspden RM. Material properties of subchondral bone from patients with osteoporosis or osteoarthritis by microindentation testing and electron probe microanalysis. Calcif Tissue Int. 2003;73:66–71.
  19. Kourkoumelis N, Balatsoukas I, Tzaphlidou M. Ca/P concentration ratio at different sites of normal and osteoporotic rabbit bones evaluated by Auger and energy dispersive X-ray spectroscopy. J Biol Phys. 2012;38:279–291.
  20. Feng JY, Xu Y, Barauskas O, et al. Role of mitochondrial RNA polymerase in the toxicity of nucleotide inhibitors of hepatitis C virus. Antimicrob Agents Chemother. 2015;60:806–817.
  21. Arnold JJ, Sharma SD, Feng JY, et al. Sensitivity of mitochondrial transcription and resistance of RNA polymerase II dependent nuclear transcription to antiviral ribonucleosides. PLoS Pathog. 2012;8:e1003030.
  22. Issa NM, El-Sherif NM. Light and electronic histological studies to the effect of Sofosbuvir on the visual cerebral cortex of adult male albino rat. J Am Sci. 2017;13:79–87.
  23. Betteridge DJ. What is oxidative stress? Metabolism. 2000;49:3–8.
  24. Wauquier F, Leotoing L, Coxam V, Guicheux J, Wittrant Y. Oxidative stress in bone remodeling and disease. Trends Mol Med. 2009;15:468–477.
  25. Moon H, Kim SE, Yun YP, et al. Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species. Exp Mol Med. 2011;43:605–612.
  26. Shih CM, Ko WC, Wu JS, et al. Mediating of Caspase independent apoptosis by cadmium through the mitochondria-ROS pathway in MRC-5 fibroblasts. J Cell Biochem. 2004;91:384–397.
  27. Zhao H, Liu W, Wang Y, et al. Cadmium induces apoptosis in primary rat osteoblasts through Caspase and mitogen-activated protein kinase pathways. J Vet Sci. 2015;16:297–306.
  28. Bhatia HK, Singh H, Grewal N, Natt NK. Sofosbuvir: A novel treatment option for chronic hepatitis C infection. J Pharmacol Pharmacother. 2014;5:278–284.
  29. Yonova D. Pruritis in certain internal diseases. Hippokratia. 2007;11:67–71.
  30. Lesclous P, Schramm F, Gallina S, Baroukh B, Guez D, Saffar JL. Histamine mediates osteoclastic resorption only during the acute phase of bone loss in ovariectomized rats. Exp Physiol. 2006;91:561–570.