The study of the subchronic toxicity of the cream with cerium dioxide nanoparticles in cutaneous application in rabbits

Authors

DOI:

https://doi.org/10.24959/cphj.19.1483

Keywords:

cerium dioxide nanoparticles, subchronic toxicity, non-clinical studies, cutaneous application, Chinchilla rabbits

Abstract

The development of photoprotectors with cerium dioxide nanoparticles (CDN) for prevention of sunburns and skin cancer is expedient.

Aim. To study the subchronic toxicity of the cream with CDN in cutaneous application in rabbits.

Materials and methods. The cream with 0.25 % CDN in the doses of 0.06, 0.18, and 0.60 g/kg was applied cutaneously to Chinchilla rabbits for 90 days. The toxicity was assessed by the general state, behavior of animals, the body mass dynamics, and blood hematological and biochemical indices.

Results. The repeated cutaneous application of the cream with CDN in the doses of 0.06, 0.18, and 0.60 g/kg in rabbits did not cause significant changes in the general state and behavior of animals, consumption of food and water, the body mass dynamics, and blood hematological (hemoglobin level, erythrocyte, leukocyte, and thrombocyte count, leukogram) and biochemical (total protein, albumin, glucose, cholesterol, potassium, sodium, and chloride levels, ALT and AST activity) indices. After 1 month of application of the cream in the dose of 0.60 g/kg the glucose level was 44.5 % higher than in the intact control group, but in 3 months of the experiment differences in this parameter disappeared.

Conclusions.The data obtained concerning the safety of the cream with CDN determined the expediency of further non-clinical studies of this photoprotector.

 

Author Biographies

G. V. Zaychenko, "Bogomolets National Medical University"

head of the Department of Pharmacology Bogomolets National Medical University

O. A. Pokotylo, "Bogomolets National Medical University"

teaching assistant of the Department of Pharmacology

N. S. Nikitina, "SOE "State Scientific Centre of Drugs and Healthcare Products"

employee

References

Kolesnik, O. O., Fedorenko, Z. P., Mykhailovych, Yu. Y., Hulak, L. O., Horokh, Ye. L., … Ryzhov, A. Yu. (2018). Biuleten Natsionalnoho kantser-reiestru № 19 – ‘Rak v Ukraini, 2016–2017’. Kyiv: Natsionalnyi instytut raku

Apalla, Z., Nashan, D., Weller, R. B., & Castellsagué, X. (2017). Skin Cancer: Epidemiology, Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches. Dermatology and Therapy, 7(S1), 5–19.https://doi.org/10.1007/s13555-016-0165-y

Guy, G. P., & Ekwueme, D. U. (2011). Years of potential life lost and indirect costs of melanoma and non-melanoma skin cancer: a systematic review of the literature. Pharmacoeconomics, 29 (10), 863–874. https://doi.org/10.2165/11589300-000000000-00000

Wu, S., Cho, E., Li, W.-Q., Weinstock, M. A., Han, J., & Qureshi, A. A. (2016). History of Severe Sunburn and Risk of Skin Cancer Among Women and Men in 2 Prospective Cohort Studies. American Journal of Epidemiology, 183(9), 824–833. https://doi.org/10.1093/aje/kwv282

Martens, M. C., Seebode, C., Lehmann, J., & Emmert S. (2018). Photocarcinogenesis and skin cancer prevention strategies: an update. Anticancer Research, 38 (2), 1153–1158. https://doi.org/10.21873/anticanres.12334

Stiefel, C., & Schwack, W. (2014). Photoprotection in changing times - UV filter efficacy and safety, sensitization processes and regulatory aspects. International Journal of Cosmetic Science, 37(1), 2–30. https://doi.org/10.1111/ics.12165

Gulson, B., McCall, M. J., Bowman, D. M., & Pinheiro, T. (2015). A review of critical factors for assessing the dermal absorption of metal oxide nanoparticles from sunscreens applied to humans, and a research strategy to address current deficiencies. Archives of Toxicology, 89(11), 1909–1930. https://doi.org/10.1007/s00204-015-1564-z

Ruszkiewicz, J. A., Pinkas, A., Ferrer, B., Peres, T. V., Tsatsakis, A., & Aschner, M. (2017). Neurotoxic effect of active ingredients in sunscreen products, a contemporary review. Toxicology Reports, 4, 245–259. https://doi.org/10.1016/j.toxrep.2017.05.006

Merkus, H.G., & Meesters, G.M.H. (Eds.). (2014). Particulate products: tailoring properties for optimal performance. Basel: Springer International Publishing Switzerland

Shcherbakov, A. B., Ivanova, O. S., Spivak, N. Ya., Kozyk, V. V., & Ivanov, V. K. (2016). Sintez i biomeditsinskie primeneniia nanodispersnogo dioksida tseriia. Tomsk: Izdatelskii dom Tomskogo gosudarstvennogo universiteta

Caputo, F., De Nicola, M., Sienkiewicz, A., Giovanetti, A., Bejarano, I., Licoccia, S., … Ghibelli, L. (2015). Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis. Nanoscale, 7(38), 15643–15656. https://doi.org/10.1039/c5nr03767k

Stefanov, O. V. (Ed.). (2001). Doklinichni doslidzhennia likarskykh zasobiv: metodychni rekomendatsii. Kyiv: Avitsena.

Zapadniuk, I. P., Zapadniuk, V. I., Zakhariia, E. A., & Zapadniuk, B. V. (1983). Laboratornye zhyvotnye. Razvedenie, soderzhanie, ispolzovanie v eksperimente. Kyiv: Vyshcha shkola. Golovnoe izdatelstvo.

Ramesh, A., Ratla, N. N., Indukuri, R., Venkatesh, K., & Rao, S. T. (2014). Acute and sub-acute oral toxicity assessment of the cerium oxide nanoparticles in Wistar rats. International Journal of Phytopharmacology, 5 (1), 46–50.

Shanker, K., Naradala, J., Mohan, G. K., Kumar, G. S., & Pravallika, P. L. (2017). A sub-acute oral toxicity analysis and comparative in vivo anti-diabetic activity of zinc oxide, cerium oxide, silver nanoparticles, and Momordica charantia in streptozotocin-induced diabetic Wistar rats. RSC Advances, 7(59), 37158–37167. https://doi.org/10.1039/c7ra05693a

Downloads

Published

2019-03-04

Issue

Section

Pre-clinical studies of new drugs