Immunohistochemical characteristics of inducible nitric oxide synthase and estrogen receptors alpha expression in patients with keratoderma climactericum

H. I. Makurina; S. I. Tertyshnyi; V. H. Siusiuka; O. V. Veretelnyk; O. K. Synakh

doi:10.14739/2310-1210.2022.4.257518

Authors

H. I. Makurina Zaporizhzhia State Medical University, Ukraine, Ukraine https://orcid.org/0000-0002-3293-2748
S. I. Tertyshnyi Zaporizhzhia State Medical University, Ukraine, Ukraine https://orcid.org/0000-0003-3856-4234
V. H. Siusiuka Zaporizhzhia State Medical University, Ukraine, Ukraine https://orcid.org/0000-0002-3183-4556
O. V. Veretelnyk Zaporizhzhia State Medical University, Ukraine, Ukraine https://orcid.org/0000-0003-2433-717X
O. K. Synakh Zaporizhzhia State Medical University, Ukraine, Ukraine https://orcid.org/0000-0002-6626-7723

DOI:

https://doi.org/10.14739/2310-1210.2022.4.257518

Keywords:

palmoplantar keratoderma, climacteric, inducible nitric oxide synthase, estrogen receptor alpha, pathomorphological and immunochemical studies

Abstract

Aim. To examine the characteristics of immunohistochemical expression of inducible nitric oxide synthase and estrogen receptors alpha in patients with keratoderma climactericum compared to postmenopausal women with clinically intact skin, to reveal possible correlation between these markers’ expression levels and pathomorphogenesis of menopausal keratoderma.

Materials and methods. The pathomorphological and immunohistochemical analysis was performed on the biopsy material of 22 patients with keratoderma climactericum, who constituted the study group, and on the autopsy material from 32 women in a postmenopausal period without any signs of climacteric keratoderma, who were considered as a control group.

Results. A significant difference was found in the area and intensity of inducible nitric oxide synthase expression between the study group diagnosed with keratoderma climactericum and the control group with unaffected skin, with increasing expression parameters among patients with keratoderma. A significant difference was also observed in the area and intensity of estrogen receptors alpha expression between the study and the control group, this time with increasing expression parameters among the control group.

Conclusions. Patients with keratoderma climactericum demonstrate statistically significantly higher levels of nuclear and cytoplasmatic expression of inducible nitric oxide synthase in epidermal and dermal cells than individuals from the control group, which may indicate acute inflammation as a part of climacteric keratoderma pathogenesis. The area and intensity of estrogen receptors alpha expression in material from patients diagnosed with menopausal keratoderma are lower than in the material from the control group, which demonstrates a correlation between estrogen-deficient state in postmenopausal period and the development of skin changes in women with keratoderma climactericum.

Author Biographies

H. I. Makurina, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Dermatovenereolоgy and Cosmetology with the Course of Aesthetic Medicine of Postgraduate Education Faculty

S. I. Tertyshnyi, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Pathological Anatomy and Forensic Medicine

V. H. Siusiuka, Zaporizhzhia State Medical University, Ukraine

MD, PhD, Associate Professor of the Department of Obstetrics and Gynecology

O. V. Veretelnyk, Zaporizhzhia State Medical University, Ukraine

MD, PhD, Associate Professor of the Department of Dermatovenereolоgy and Cosmetology with the Course of Aesthetic Medicine of Postgraduate Education Faculty

O. K. Synakh, Zaporizhzhia State Medical University, Ukraine

MD, Postgraduate Student of the Department of Dermatovenereolоgy and Cosmetology with the Course of Aesthetic Medicine of Postgraduate Education Faculty

References

Has, C., & Technau-Hafsi, K. (2016). Palmoplantar keratodermas: clinical and genetic aspects. JDDG: Journal Der Deutschen Dermatologischen Gesellschaft, 14(2), 123-140. https://doi.org/10.1111/ddg.12930
Bolick, N. L., Trivedi, L. E., & Elston, D. M. (2021). Thick Hyperkeratotic Plaques on the Palms and Soles. Cutis, 107(3), 128, 134-135. https://doi.org/10.12788/cutis.0200
Sinаch, O. K., & Fedotov, V. P. (2017). Osobennosti kliniko-morfologicheskikh i endokrinnykh sdvigov u bol'nykh klimaktericheskoi keratodermiei [Features of the clinical and morphological and endocrine alterations in patients with climacteric keratoderma]. Dermatovenerologiya. Kosmetologiya. Seksopatologiya, (1-4), 79-83. [in Russian].
Zapolsky, M. Ye., Lebedyuk, M. M., Frolova, A. I., Kvitko, L. P., & Nerubaschenko, S. V. (2015). Porazhenie kozhi kistei i stop pri ostrykh i khronicheskikh dermatozakh. Terapevticheskie vozmozhnosti na sovremennom etape [Skin lesions of hands and feet in acute and chronic dermatoses. Therapeutic possibilities at present stage]. Ukrainskyi zhurnal dermatolohii, venerolohii, kosmetolohii, (3), 101-108. [in Russian].
Lephart, E. D., & Naftolin, F. (2021). Menopause and the Skin: Old Favorites and New Innovations in Cosmeceuticals for Estrogen-Deficient Skin. Dermatology and Therapy, 11(1), 53-69. https://doi.org/10.1007/s13555-020-00468-7
Rzepecki, A. K., Murase, J. E., Juran, R., Fabi, S. G., & McLellan, B. N. (2019). Estrogen-deficient skin: The role of topical therapy. International journal of women's dermatology, 5(2), 85-90. https://doi.org/10.1016/j.ijwd.2019.01.001
Cinelli, M., Do, H., Miley, G., & Silverman, R. (2019). Inducible nitric oxide synthase: Regulation, structure, and inhibition. Medicinal Research Reviews, 40(1), 158-189. https://doi.org/10.1002/med.21599
Xue, Q., Yan, Y., Zhang, R., & Xiong, H. (2018). Regulation of iNOS on Immune Cells and Its Role in Diseases. International journal of molecular sciences, 19(12), 3805. https://doi.org/10.3390/ijms19123805
Zhao, R., Guan, D. W., & Lu, B. (2005). Immunohistochemical study on expression of iNOS and eNOS during skin incised wound healing in mice. Fa Yi Xue Za Zhi, 21(3), 161-164.
De Souza, Á. Do P. B., de Oliveira, M. M. R., de Andrade, R. R., de Amorim, R. F. B., Bocca, A. L., & Borin, M. de F. (2017). The in vivo effect of L-arginine on skin elasticity in mice. Brazilian Journal of Pharmaceutical Sciences, 53(3). https://doi.org/10.1590/s2175-97902017000300045
Samaka, R. M., Bakry, O. A., Shoeib, M. A., & Zaaza, M. M. (2014). Expression of iNOS and NF-κB in melasma: an immunohistochemical study. Analytical and quantitative cytopathology and histopathology, 36(5), 245-257.
Makurina, G. І., & Baudarbekova, M. М. (2016). Osoblyvosti aktyvnosti iNOS u vohnyshchakh urazhenoi shkiry khvorykh na psoriaz iz suputnoiu arterialnoiu hipertenziieiu [Features of iNOS activity in the skin lesions of patients with psoriasis and concomitant hypertension]. Pathologia, (2), 40-46. [in Ukrainian]. https://doi.org/10.14739/2310-1237.2016.2.80990
Ding, Z., Ogata, D., Roszik, J., Qin, Y., Kim, S. H., Tetzlaff, M. T., Lazar, A. J., Davies, M. A., Ekmekcioglu, S., & Grimm, E. A. (2021). iNOS Associates With Poor Survival in Melanoma: A Role for Nitric Oxide in the PI3K-AKT Pathway Stimulation and PTEN S-Nitrosylation. Frontiers in oncology, 11, 631766. https://doi.org/10.3389/fonc.2021.631766
Lind, M., Hayes, A., Caprnda, M., Petrovic, D., Rodrigo, L., Kruzliak, P., & Zulli, A. (2017). Inducible nitric oxide synthase: Good or bad?. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 93, 370-375. https://doi.org/10.1016/j.biopha.2017.06.036
Lephart, E. D. (2018). A review of the role of estrogen in dermal aging and facial attractiveness in women. Journal of cosmetic dermatology, 17(3), 282-288. https://doi.org/10.1111/jocd.12508
Liu, T., Li, N., Yan, Y. Q., Liu, Y., Xiong, K., Liu, Y., Xia, Q. M., Zhang, H., & Liu, Z. D. (2020). Recent advances in the anti-aging effects of phytoestrogens on collagen, water content, and oxidative stress. Phytotherapy research : PTR, 34(3), 435-447. https://doi.org/10.1002/ptr.6538