Morphofunctional Assessment of the Magnocellular Hypothalamic Nuclei in Rats following Intragastric Administration of Formalin and Hydrogen Peroxide and Supplementary Oxytocin Treatment

The aim of the study was to assess the morphofunctional state of the supraoptic and paraventricular nuclei of the hypothalamus in rats following long-term intragastric administration of formalin and hydrogen peroxide, as well as additional oxytocin exposure.

Material and methods. A comparative assessment of the morphofunctional state of the magnocellular (supraoptic and paraventricular) hypothalamic nuclei was performed in two groups of rats (n=30, male Wistar rats, weighing 190–210 g). Over a period of 6 months, each group of animals received intragastric administration of a mixture of 0.4% formaldehyde solution and 0.4% hydrogen peroxide solution in a 1:1 ratio. The second group of animals additionally received an intramuscular injection of oxytocin at a dose of 0.5 μg. Paraffin sections, 4–5 μm thick, were stained with Mayer's hematoxylin and eosin, as well as with Gomori–Gabe stain. Nonparametric statistical methods using STATISTICA 6.0 software were employed for data analysis. Statistical processing included the calculation of quantitative data presented as median and interquartile range (25th and 75th percentiles) in the format Me [Q1; Q3].

Results. After 6 months of administration of the formalin and hydrogen peroxide mixture in the group of animals without additional oxytocin administration, a comparative assessment of the morphofunctional state of neurosecretory cells (NSCs) of the supraoptic and paraventricular hypothalamic nuclei was performed. It was found that under conditions of prolonged exposure to formaldehyde and hydrogen peroxide in experimental animals, blockade of neurosecretory release and depletion of secretory mechanisms of the magnocellular hypothalamic nuclei (particularly NSCs of the paraventricular nuclei) were observed. Against the background of oxytocin administration, adaptive processes were noted in the hypothalamic–pituitary neurosecretory system in response to exposure to the formalin and hydrogen peroxide mixture.

Conclusion. Oxytocin administration altered the morphofunctional state of the studied hypothalamic NSCs: the proportion of pyknomorphic cells decreased, and the vessels of the microvasculature and ependymocytes of the third ventricle showed no destructive changes.

1. Avtandilov GG. Vvedenie v kolichestvennuyu patologicheskuyu morfologiyu.[Introduction to quantitative pathological morphology]. Moscow: Meditsina; 1980. 216 p. (In Russ.).

2. Bukharin OV, Stadnikov AA, Perunova NB. Rol' oksitotsina i mikrobioty v regulyatsii vzaimodeistvii pro- i eukariot pri infektsii. [The role of oxytocin and microbiota in the regulation of proand eukaryotic interactions during infection]. Yekaterinburg: UrO RAN; 2018. 247 p. (In Russ.).

3. Senchukova MA, Stadnikov AA, Kozlov AV, Bokov DA. Patent RF №2401463; 2009. (In Russ.).

4. Pearse AGE. Gistokhimiya teoreticheskaya i prikladnaya. [Histochemistry: theoretical and applied]. Moscow: Izdatel'stvo inostrannoi literatury; 1956. 488 p.

5. Behtaji S, Ghafouri-Fard S, Sayad A, Sattari A, Rederstorff M, Taheri M. Identification of oxytocin-related lncRNAs and assessment of their expression in breast cancer. Sci Rep. 2021 Mar 19;11(1):6471. doi: 10.1038/s41598-021-86097-2.

6. Carter CS, Kenkel WM, MacLean EL, Wilson SR, Perkeybile AM, Yee JR, et al. Is Oxytocin "Nature's Medicine"? Pharmacol Rev. 2020 Oct;72(4):829- 861. doi: 10.1124/pr.120.019398.

7. Costa S, Costa C, Madureira J, Valdiglesias V, Teixeira-Gomes A, Guedes de Pinho P, et al. Occupational exposure to formaldehyde and early biomarkers of cancer risk, immunotoxicity and susceptibility. Environ Res. 2019 Dec;179(Pt A):108740. doi: 10.1016/j.envres.2019.108740.

8. Fenech M, Nersesyan A, Knasmueller S. A systematic review of the association between occupational exposure to formaldehyde and effects on chromosomal DNA damage measured using the cytokinesis-block micronucleus assay in lymphocytes. Mutat Res Rev Mutat Res. 2016 Oct-Dec;770(Pt A):46-57. doi: 10.1016/j.mrrev.2016.04.005.

9. Hatton GI. Function-related plasticity in hypothalamus. Annu Rev Neurosci. 1997;20:375-97. doi: 10.1146/annurev.neuro.20.1.375.

10. Liu H, Gruber CW, Alewood PF, M?ller A, Muttenthaler M. The oxytocin receptor signalling system and breast cancer: a critical review. Oncogene. 2020 Sep;39(37):5917-5932. doi: 10.1038/s41388-020-01415-8.

11. Liu Z, Wang H, Zhang C, Qi H, Li Z, Sun Y, et al. The interplay between oxytocin receptor and YAP in regulating gastric cancer progression. Oncogene. 2025 Sep;44(34):3126-3141. doi: 10.1038/s41388-025-03480-3.

12. Mehdi SF, Pusapati S, Khenhrani RR, Farooqi MS, Sarwar S, Alnasarat A, et al. Oxytocin and Related Peptide Hormones: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis. Front Immunol. 2022 Apr 29;13:864007. doi: 10.3389/fimmu.2022.864007.

13. Steele SR, Ratuski AS, Hui EI, Mahoney BS, Geronimo JT, Huss MK, et al. Oxytocin administration rescues the negative impacts of social isolation on wound healing in mice. Horm Behav. 2025 May;171:105741. doi: 10.1016/j.yhbeh.2025.105741.

14. Szeto A, Cecati M, Ahmed R, McCabe PM, Mendez AJ. Oxytocin reduces adipose tissue inflammation in obese mice. Lipids Health Dis. 2020 Aug 20;19(1):188. doi: 10.1186/s12944-020-01364-x.

15. Tabak BA, Leng G, Szeto A, Parker KJ, Verbalis JG, Ziegler TE, et al. Advances in human oxytocin measurement: challenges and proposed solutions. Mol Psychiatry. 2023 Jan;28(1):127-140. doi: 10.1038/s41380-022-01719-z