PECULIARITIES OF MICROSTRUCTURAL CHANGES IN THE KIDNEYS OF WHITE RATS AND THEIR DYNAMICS IN CASE OF SUDDEN WITHDRAWAL OF DEXAMETHASONE AFTER ITS PROLONGED ADMINISTRATION IN HIGH DOSES
DOI:
https://doi.org/10.11603/1811-2471.2024.v.i2.14725Keywords:
kidneys, dexamethasone, glomeruli, capsules, arteriesAbstract
SUMMARY. It is known that the sudden withdrawal of glucocorticoids after their prolonged administration in high doses causes changes in the body that are called "acute hypocorticism" or "Addisonian crisis".
The aim – to determine the peculiarities of structural changes in the components of the renal parenchyma and in the bloodstream of the kidneys of white rats during prolonged administration of dexamethasone in high doses and after its sudden withdrawal.
Material and Methods. The experiments were performed on white laboratory rats, which were divided into 3 groups: control, animals to which dexamethasone was administered for a long time in high doses and animals that were suddenly discontinued from dexamethasone.
Results. Prolonged (for 28 days) administration of dexamethasone in high doses to white rats was accompanied by a decrease in the capacity of small arteries and arterioles due to increased tone and thickening of their middle membranes with narrowing of the lumen, as well as by a decrease in filling of capillary glomeruli with blood and a reduction of their area with a simultaneous increase of the area of the urinary spaces of Shumlansky-Bowman capsules.
Sudden withdrawal of dexamethasone resulted in reverse remodelling of the structural components of the kidneys. The characteristic feature of the experiment between day 1 and day 7 was the restoration of the morphological and functional state of the structures in which certain changes occurred after dexamethasone administration. The changes developed into quite pronounced dilatation reactions of intra-organic arteries of all levels of branching on the 14th day. The dilation of the vessel lumens was combined with a low level of filling them with blood. It is obvious that the 14th day of observation was a critical period in the disruption of intra-organic renal circulation with corresponding dystrophic changes in the parenchyma, because later there were reversible changes with gradual recovery of both blood circulation and morphological and functional state of the structural components of the kidneys of experimental animals.
Conclusions. Sudden withdrawal of dexamethasone after its prolonged administration in high doses is initially accompanied by a gradual restoration of the morphological and functional state of intra-organic vessels and renal corpuscles compared with the state that developed during the administration of the drug.
From day 7 to 14, the progression of dilated renal artery remodelling leads to the development of secondary adrenal cortical insufficiency.
In the long term experiment (14–28 days), the morphological and functional state of the structural components of the kidneys is restored again after the adrenal crisis.
References
Havrysiuk, V.K., & Humeniuk, H.L. (2015). Hliukokortykoidy u likuvanni khvorykh na bronkhoobstruktyvni ta interstytsiini zakhvoriuvannia lehen [Glucocorticoids in the treatment of patients with broncho-obstructive and interstitial lung diseases]. Ukr. Pulmonol. zhurnal. – Ukr. Pulmonol. Journal, 2, 34-36 [in Ukrainian].
Bychenko, O.V., & Lytvynenko, A.V. (2017). Systemna hliukokortykosteroidna terapiia [Systemic glucocorticosteroid therapy]. Ukr pulmonol zhurnal – Ukr. Pulmonol. Journal, 4, 62–67 [in Ukrainian].
Chotiyarnwong, P., & McCloskey, E.V. (2020). Pathogenesis of glucocorticoid-induced osteoporosis and options for treatment. Nature Reviews Endocrinology, 16, 437-447. DOI: 10.1038/s41574-020-0341-0.
Burmester, G.R., Buttgereit, F., Bernasconi, C., Álvaro-Gracia, C.M., Castro, N., & Dougados, M. (2020). Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial. Lancet, 396(10246), 267-276. DOI: 10.1016/S0140-6736(20)30636-X.
Khodosh, E.M., Nartov, P.V., Yakovenko, O.K., Asoian, I.M., & Syrota, V.V. (2023). Lohika hliukokortykoidnoi terapii [The logic of glucocorticoid therapy]. Astma ta alerhiia – Asthma and allergy, 1, 63-71 [in Ukrainian].
Herman, O. M. (2021). Osoblyvosti strukturnykh zmin v yaiechkakh shchuriv pry tryvalomu vvedenni prednizolonu u vysokykh dozakh ta raptovii yoho vidmini [Peculiarities of structural changes in the testicles of rats with long-term administration of prednisolone in high doses and its sudden withdrawal]. Visnyk problem biolohii i medytsyny – Herald of problems of biology and medicine, 4(162), 256-261 [in Ukrainian].
Zolotukhina, Yu. (2020). Suchasni vyklyky ta ridkisna patolohiia v praktychnii endokrynolohii [Modern challenges and rare pathology in practical endocrinology]. Naukovo-osvitnii proekt «Shkola endokrynoloha». Zdorovia Ukrainy – “School of Endocrinologist” project for scientists and educators. Health of Ukraine, 4, 12-17. Retrieved from: https://health-ua.com/multimedia/userfiles/files/2020/Endo_4_2020/Endo_4_2020_st12-17.pdf [in Ukrainian].
Reheda, M.S., & Fedoriv, Ya.-R. M. (2013). Diahnostyka ta nevidkladna medychna dopomoha v klinitsi vnutrishnoi medytsyny [Diagnostics and emergency medical care in the clinic of internal medicine]. Lviv. Retrieved from: http://www.ifp.kiev.ua/doc/journals/aa/23/pdf23-1/63.pdf [in Ukrainian].
Piasetska, N.V., Tkachenko, R.O., & Petrychenko, V.V. (2019). Deksametazon yak komponent spinalnoi anestezii pry kesarevomu roztyni [Dexamethasone as a component of spinal anesthesia for cesarean section]. Meditsyna neotlozhnykh sostoianiy – Emergency Medicine, 2(97). Retrieved from: https://anest.vn.ua/file/papisev_06_19_1.pdf [in Ukrainian].
Hardner, Dеvyd, & Shobek, Dolores. (2017). Bazysnaia y klynycheskaia еndokrynolohyia. Knyha 2. [Basic and clinical endocrinology. Book 2]. Moscow: Bynom. Laboratoryia znaniy [in Russian].
Dinsen, S., Baslund B., & Klose M. (2013). Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself. European Jornal of Internal Medicine, 24(8), 714-720.
