Development of oxidative stress in different experimental models of hypothyroidism in immature rats

Summary. Hypothyroidism is one of the common pathologies in the practice of endocrinologist. Autoimmune thyroiditis and alimentary iodine deficiency are the causes of hypothyroidism. Hypothyroidism is especially dangerous in children. An experiment study the pathology of the disease. Today there are several models of experimental hypothyroidism: surgical removal of the thyroid gland or thyrostatics using (thiourea derivatives – propylthiouracil, metamazole, mercazolyl, thyroperoxidase blockers – thiamazole), per os for 1–8 weeks. The aim of the study – to investigate the processes of lipid peroxidation in immature rats in the simulation of hypothyroidism by thyroidectomy, mercazolyl using and a combination of both methods. Materials and Methods. The experiments performed on 75 white sexually immature male rats aged 1.5–2.0 months of 3 groups. Group 1 – hypothyroidism was induced by mercazolyl (75 mg/kg of body weight for 14 days), group 2 – by thyroidectomy, group 3 – by the combination of the first two methods. Serum levels of diene conjugates (DC), TBA-active products, superoxide dismutase (SOD) and catalase activity were determined. Results. The results of the examination of rats indicate that each of the proposed methods can achieve a deep hypothyroid state. The efficiency of expression of hypothyroidism models for lipid peroxidation processes: thyroidectomy (51.2 %) → mercazolyl (76.8 %) → thyroidectomy + mercazolyl (119.5 %). In our experiments, a compensatory increase in SOD activity was noted. Changes in the increase in SOD activity were as follows: thyroidectomy + mercazolyl (1.6 times) → mercazolyl (2.6 times) → thyroidectomy (3.2 times). Catalase activity changed ambiguously: in thyroidectomy it significantly increased 2.6 times, in feeding mercazolyl did not change significantly, and in combined pathology – decreased by 44.4 %. Conclusions. 1. Thyroidectomy, mercazolyl using and its combination are reliable methods of inducing hypothyroidism in immature rats. As the hypothyroid state increases, these methods can be presented in the following order: thyroidectomy → mercazolyl → thyroidectomy + mercazolyl. 2. In hypothyroidism, the processes of lipid peroxidation activated as follows: thyroidectomy → mercazolyl → thyroidectomy + mercazolyl. In response to thyroid pathology, the superoxide dismutase activity of the blood compensatory increases: thyroidectomy + mercazolyl → mercazolyl → thyroidectomy

hypothyroidism, immature rats, experiment

https://doi.org/10.11603/bmbr.2706-6290.2022.1.12969

[1] Chiovato  L,  Magri  F,  Carle  A.  Hypothyroidism  in context:  where  we've  been  and  where  we're  going. Adv Ther. 2019;36(Suppl 2): 47-58. DOI: 10.1007/s12325-019-01080-8.

[2] Taylor  P, Albrecht  D,  Scholz A,  Gutierrez-Buey  G, Lazarus  J,  Dayan  CM,  et  al.  Global  epidemiology  of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol. 2018;14(5): 301-16. DOI: 10.1038/nrendo.2018.18.

[3] Hennessey J, Espaillat R. Subclinical hypothyroidism: a historical view and shifting prevalence. Int J Clin Pract. 2015;69(7): 771-82. DOI: 10.1111/ijcp.12619.

[4] Leng  O,  Razvi  S.  Hypothyroidism  in  the  older population. Thyroid Res. 2019;12: 2. DOI: 10.1186/s13044-019-0063-3.

[5] Biondi  B,  Cappola  AR,  Cooper  D.  Subclinical hypothyroidism: a review. JAMA. 2019;322(2): 153-60. DOI: 10.1001/jama.2019.9052.

[6] Raduchich O. Subclinical hypo- and hyperthyroidism. It should be observed or treated.  Ukrainian medical journal. 2019;2(1): 66-8.

[7] Garmendia Madariaga A, Santos Palacios S, Guillen-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014;99(3): 923-31. DOI: 10.1210/jc.2013-2409.

[8] Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter  EW,  Spencer  CA,  et.  al.  Serum  TSH,  T(4),  and thyroid antibodies in the United States population (1988 to 1994):  National  Health  and  Nutrition  Examination  Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2): 489-99. DOI: 10.1210/jcem.87.2.8182.

[9] Udovcic M, Pena R, Patham B, Tabatabai L, Kansara A.  Hypothyroidism  and  the  Heart.  Methodist  Debakey Cardiovasc J. 2017;13(2): 55-9. DOI: 10.14797/mdcj-13-2-55.

[10] Jeddi S, Zaman J, Ghasemi A. Effects of ischemic postconditioning  on  the  hemodynamic  parameters  and heart nitric oxide levels of hypothyroid rats. Arq Bras Cardiol. 2015;104(2): 136-43. DOI: 10.5935/abc.20140181.

[11] Tomczyk   T,   Urbanska   E.   Experimental hypothyroidism raises brain kynurenic acid - Novel aspect of thyroid dysfunction. Eur J Pharmacol. 2020;883: 173363. DOI: 10.1016/j.ejphar.2020.173363.

[12] Atici E, Menevse E, Baltaci AK, Mogulkoc R. Both experimental hypothyroidism and hyperthyroidism increase cardiac irisin levels in rats. Bratisl Lek Listy. 2018;119(1): 32-5. doi: 10.4149/BLL_2018_007.

[13] Fun  H,  Fayfura  B.  Metabolism  of  acetylcholine in  the  myocardium  of  immature  rats  with  experimental hypothyroidism.  Klin  ta  eksperym  patol.  2004;2:  35-6. Ukrainian.

[14] Gavrilov V, Mishkorudnaya M. Spectrophotometric determination of the content of lipid hydroperoxides in blood plasma. Lab delo. 1983;3: 33-5. Russian.

[15] Korobeynikova E. Modification of the determination of LPO products in the reaction with thiobarbituric acid. Lab delo. 1989;7: 8-10. Russian.

[16] Chevari S, Chaba I, Sokei Y. The role of superoxide dismutase  in  the  oxidative  processes  of  the  cell  and  a method  for  its  determination  in  biological  materials.  Lab delo. 1985;11: 678-81. Russian.

[17] Korolyuk  M,  Ivanova  L,  Mayorova  I,  Tokarev  V. Method for determining catalase activity. Lab delo. 1988;1: 16-9. Russian.

[18] Potikha  N.  The  relationship  between  cholinergic and  adrenergic  regulation  of  heart  rate  in  immature  rats with experimental hypothyroidism. Klin ta eksperym. patol. 2004;3: 55-8. Ukrainian.

[19] Hromakova  I,  Zilberman  S,  Konovalenko  O. Age features of experimental hypothyroidism in rats. Fiziol. zh. 2002;1(48): 80-6. Ukrainian.