Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 May;28(5):615-620.
doi: 10.1016/j.jsps.2020.03.014. Epub 2020 Apr 2.

Genotoxic potential of a novel PDE-4B inhibitor Apremilast by chromosomal aberration and micronucleus assay in mice

Muhammad Afzal  1 , Imran Kazmi  2 , Khalid Saad Alharbi  1 , Anwarulabedin Mohsin Quazi  1 , Muhammad Shahid Nadeem  2 , Nasser Hadal Alotaibi  3 , Ameeduzzafar  4 , Nabil K Alruwaili  4 , Firoz Anwar  2 , Sattam Khulaif Alenezi  5 , Mohammad M Al-Sanea  6
Affiliations

Genotoxic potential of a novel PDE-4B inhibitor Apremilast by chromosomal aberration and micronucleus assay in mice

Muhammad Afzal et al. Saudi Pharm J. 2020 May.

Abstract

Objective: Researchers have confirmed that chronic administration of drugs at high doses causes genotoxicity which serve as first step in development of cancers. Apremilast, a phosphodiesterase-4 inhibitor is Food and Drug Administration (FDA) approved drug for Psoriatic Arthritis. The present study designed to conduct genotoxicity testing using the genotoxic study which give simple, sensitive, economical and fast tools for the assessment of damage of genetic material.

Methods: To conduct genotoxicity study of Apremilast, 60 Swiss albino male mice divided into 6 groups (n = 10). Group1 served as a normal control group without any treatment, Group 2 treated as a disease control and administered with cyclophosphamide 40 mg/kg, IP. Group 3, 4, 5 and 6 treated as test groups and received 10, 20, 40 and 80 mg/kg/day Apremilast respectively. The total duration of study was 13 weeks. At termination day animals were sacrificed and chromosomal aberration assay (BMCAA) and micronucleus assay (BMMNA) were performed to know the genotoxicity potential of Apremilast.

Results: The results indicates significant rise in chromosomal aberrations (CA) frequency in bone marrow cells and decrease in the MI of the disease control animals as well as Apremilast treated groups. Further significant (p < 0.001; p < 0.0001) increase in score of micronucleated polychromatic erythrocytes (MNPCEs) and percentage of micronucleated PCEs per 1000 PCEs and decrease in the ratio of polychromatic/normochromatic erythrocytes (PCE/NCE) was observed in micronucleus assay. Genotoxic effect increases with the increase of Apremilast dose. Conclusion: Finding of present indicates that Apremilast shows genotoxic potential on high administration although further detailed toxicity studies required for confirmations.

Keywords: Apremilast; Chromosomal aberration; Cyclophosphamide; Genetic damage; Genotoxicity; Mice.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Effect of Apremilast on score of micronucleated PCEs in 1000 PCEs. Results are mean ± SEM (n = 6). Significance: (#) Group 2 (cyclophosphamide control) as compared to normal control. (*) Groups as compared to disease control. *P < 0.05;**P < 0.01; ***P < 0.001.
Fig. 2
Fig. 2
Effect of Apremilast on percentage of micronucleated PCEs/1000 PCEs. Results are mean ± SEM (n = 6). Significance: (#) Group 2 (cyclophosphamide control) as compared to normal control. (*) Groups as compared to disease control. *P < 0.05;**P < 0.01; ***P; ns: non-significant.
Fig. 3
Fig. 3
Effect of Apremilast on the ratio of polychromatic/normochromatic erythrocytes (PCE/NCE). Significance: (#) Group 2 (cyclophosphamide control) as compared to normal control. (*) Groups as compared to disease control. *P < 0.05;**P < 0.01; ***P; ns: non-significant.
See this image and copyright information in PMC

References

    1. Alshahrani S., Tripathi P., Alhazmi H.A., Hussain S.M., Siddiqui A.H., Ahsan W., Bratty M.A. Genotoxicity of yellow shammah (smokeless tobacco) in murine bone marrow cells in vivo. Drug Chem. Toxicol. 2019:1–6. - PubMed
    1. Anderson D., Bishop J.B., Garner R.C., Ostrosky-Wegman P., Selby P.B. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat. Res. 1995;330:115–181. - PubMed
    1. Bagri P., Jain S.K. Assessment of acetamiprid-induced genotoxic effects in bone marrow cells of Swiss albino male mice. Drug Chem. Toxicol. 2019;42(4):357–363. - PubMed
    1. Bedekovics J., Irsai G., Hegyi K., Beke L., Krenács L., Gergely L., Méhes G. Mitotic index determined by phosphohistone H3 immunohistochemistry for precise grading in follicular lymphoma. Appl. Immunohistochem. Mol. Morphol. 2018;26:579–585. - PubMed
    1. Bila J., Sretenovic A., Jelicic J., Tosic N., Glumac I., Fekete M.D., Antic D., Balint M.T., Markovic O., Milojevic Z., Radojkovic M., Trajkovic G., Puric M., Pavlovic S., Mihaljevic B. Prognostic significance of cereblon expression in patients with multiple myeloma. Clin. Lymphoma Myeloma Leuk. 2016;16:610–615. - PubMed

LinkOut - more resources