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Influence of the treatment with the antineoplastic agents 5-fluorouracil and cisplatin on the severity of experimental periodontitis in rats

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Abstract

Purpose

The determination on how antineoplastic agents interfere on the progression of periodontitis is critical for improvement and even development of novel therapeutic approaches for periodontal management. This study evaluated the influence of chemotherapy with 5-fluorouracil (5-FU) or cisplatin (CIS) on healthy periodontal tissues and on the progression of experimental periodontitis (EP).

Methods

One hundred forty-four male rats were divided into six groups (n = 24). Each group was treated with physiological saline solution (PSS) 0.9%, 5-FU, or CIS. Experimental periodontitis (EP) was induced by ligature placement. Animals were euthanized at 7, 15, and 30 days after treatment. Data were statistically analyzed (p ≤ 0.05).

Results

The groups with EP and treated with 5-FU or CIS showed lower percentage of bone volume in the furcation region and higher percentage of alveolar bone loss, higher number of TRAP-positive cells, and lower number of PCNA-positive cells when compared group with EP and treated with PSS (p ≤ 0.05). Groups with EP and treated with 5-FU or CIS showed high immunolabelling pattern of RANKL, TNF-α, and IL-1β, moderate of BAX, and low of HIF-1α. Histological analysis showed severe tissue breakdown in the groups with EP and treated with 5-FU or CIS.

Conclusions

Chemotherapy with antineoplastic agents 5-FU and CIS increased the intensity and duration of the inflammation and compromised tissue repair by reduction in cellular and vascular turnover. The more severe periodontal breakdown was caused by 5-FU.

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Notes

  1. 5-FU: 5-fluorouracil.

  2. CIS: cisplatin.

  3. EP: experimental periodontitis.

  4. SRP: scaling and root planning.

  5. PABL: percentage of alveolar bone loss.

  6. PSS: physiological saline solution.

  7. µCT: microcomputed tomography.

  8. TRAP: tartrate-resistant acid phosphatase.

  9. RANKL: receptor activator of nuclear factor kappa-Β ligand.

  10. OPG: osteoprotegerin.

  11. TNF-α: tumor necrosis factor-alfa.

  12. IL-1β: interleukin 1 beta.

  13. PCNA: proliferating cell nuclear antigen.

  14. BAX: bcl-2-associated X protein.

  15. HIF-1α: hypoxia-inducible factor 1 alpha.

  16. PBTV: percentage of bone tissue volume.

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Acknowledgements

The authors thank the Periodontics Division, the Department of Basic Sciences of the School of Dentistry, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil, and São Paulo State University (UNESP), School of Veterinary Medicine, Araçatuba. The authors also thank CAPES for providing scholarship to Dr. Vivian Novaes, and São Paulo State Foundation for Research (FAPESP) for the research grant conceded to Dr. Juliano Milanezi de Almeida (#2014/11427-8). Also, Clara Possarle Cunha (#2015/21332-7) and Giovani Lopes Fernandes (#2015/04639-1) received scholarships from FAPESP.

Funding

Dr. Juliano Milanezi de Almeida received a grant from the São Paulo State Foundation for Research- FAPESP (#2014/11427–8).

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Authors and Affiliations

  1. Department of Diagnosis and Surgery, Division of Periodontics, School of Dentistry of Araçatuba, São Paulo State University (UNESP), St. José Bonifácio 1193 - Vila Mendonça, Araçatuba, SP, 16015-050, Brazil

    Vivian Cristina Noronha Novaes, Giovani Lopes Fernandes, Clara Possarle Cunha, Leticia Helena Theodoro, Valdir Gouveia Garcia & Juliano Milanezi de Almeida

  2. Department of Basic Science, Histology Division, School of Dentistry of Araçatuba, São Paulo State University (UNESP), Araçatuba, SP, Brazil

    Edilson Ervolino

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  1. Vivian Cristina Noronha Novaes
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Contributions

VCNN, EE, and JMA have made substantial contributions to conception and design of the study. GLF and CPC have been involved in animal surgery, laboratory processing, and data collection. VCNN have been involved in conception, study design, animal surgery, laboratory processing, data interpretation, and drafting the manuscript. EE have been involved in study design, histological and immunohistochemical analysis, and critically revised the manuscript. JMA have been involved in conception, study design, data interpretation, statistical procedures, and critically revised the manuscript. LHT and VGG have critically revised the manuscript. All authors have given final approval of the version to be published.

Corresponding author

Correspondence to Juliano Milanezi de Almeida.

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All protocols were approved by Ethics Committee in Animal Use (#2014/00543) of the School of Dentistry of Araçatuba, São Paulo State University (UNESP).

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Novaes, V.C.N., Ervolino, E., Fernandes, G.L. et al. Influence of the treatment with the antineoplastic agents 5-fluorouracil and cisplatin on the severity of experimental periodontitis in rats. Support Care Cancer 30, 1967–1980 (2022). https://doi.org/10.1007/s00520-021-06586-y

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