Effects of neonatal injection of streptozotocin on biochemical indicators and oxidative stress in rats

Authors

Keywords:

diabetes mellitus, experimental, kidney, liver, oxidative stress, rats, streptozotocin, hyperglycemia

Abstract

Introduction: Streptozotocin is currently one of the most used diabetogenic agents to generate biological models of diabetes due to its chemical properties, so it is necessary to study the consequences of STZ for the organism of the laboratory animal.

Objective: To evaluate in a period of 90 days the effects of neonatal injection of streptozotocin in Wistar rats on biochemical indicators and oxidative stress in liver and kidney.

Methods: Diabetes was induced neonatally by 100 mg of streptozotocin in Wistar rats. Blood glucose, insulin and oxidative stress indicators in liver and kidney were determined in 5 animals per group at days 5, 10, 20, 30, 60, 90 of birth.

Results: Blood glucose and insulin showed significant differences in the STZ-group respect to the control group in all interventions. The maximum value of hyperglycemia was observed on day-5. The concentration of nitrates and nitrites in liver was higher than in kidney. In liver tissue of the STZ-group, this indicator was significantly higher on days 10-20 compared to the control. In all interventions, reduced glutathione consumption was demonstrated in the STZ-group compared to control in both organs. In the liver of STZ rats no lipid or protein damage was demonstrated. However, in the kidney, significant damage in both biomolecules was detected in the STZ-group on day-5.

Conclusions: Neonatal streptozotocin cytotoxicity as well as induced glucose and insulin concentrations had a negative impact on oxidative stress indicators studied in liver and kidney tissue.

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Author Biography

Leticia Bequer Mendoza, Universidad de Ciencias Médicas de Villa Clara, Cuba.

Unidad de Investigaciones Biomédicas

References

1. Radenkovi´c M, Stojanovi´c M, Prostran M. Experimental diabetes induced by alloxan and streptozotocin: The current state of the art J Pharmacol Toxicol Methods. 2015;78:13-31. DOI: 10.1016/j.vascn.2015.11.004

2. Goyal SN, Reddya NM, Patilb KR, Nakhatec KT, Ojhad S, Patil CR, et al. Challenges and issues with streptozotocin-induced diabetes–A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chemico-Biological Interactions. 2016;244:49-63. DOI: 10.1016/j.cbi.2015.11.032

3. Bequer L, Gómez T, Molina JL, Artiles D, Bermúdez R, Clapés S. Acción diabetogénica de la estreptozotocina en un modelo experimental de inducción neonatal. Biomédica. 2016;26(2):230-8. DOI: 10.7705/biomedica.v36i2.2686

4. Rendon l, Zuluaga A, Rodríguez C, Agudelo M, Vesga O. Obtención de un modelo múrido de diabetes inducida por estreptozotocina útil en la evaluación farmacodinámica de la insulina regular. Vitae. 2017;24(2):11-8. DOI: 10.17533/udea.vitae.v24n2(2)a02

5. Barrière DA, Noll C, Roussy G, Lizotte F, Kessai A, Kirby K, et al. Combination of high-fat/highfructose diet and low-dose streptozotocin to model long-term type-2 diabetes complications. SCIENTIFIC REPORTS. 2018;8(424):1-17. DOI: 10.1038/s41598-017-18896-5

6. Maqbool M, Dar MA, Gani I, Mir SA. Animal Models in Diabetes Mellitus: An Overview. Journal of Drug Delivery and Therapeutics. 2019;9(1-s):472-75. DOI: 10.22270/jddt.v9i1-s.2351

7. King A, Austin A. Animal Models of Type 1 and Type 2 Diabetes Mellitus. In: Conn PM, editor. Animal Models for the Study of Human Disease. 2nd ed. Texas: Elsevier; 2017. p. 245-65.

8. Kiss AC, Woodside B, Sinzato YK, Bernardi MM, Kempinas WG, Anselmo-Franci JA, et al. Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats. Diabetol Metab Syndr. 2013;5(61):2-10. DOI: 10.1186/1758-5996-5-61

9. Bequer L, Gómez T, Molina J, Álvarez A, Chaviano C, Clapés S. Experimental diabetes impairs maternal reproductive performance in pregnant Wistar rats and their offspring. Systems Biology in Reproductive Medicine. 2018;64(1):60-70. DOI: 10.1080/19396368.2017.1395928

10. AlFaris N, Alshammari G, Alsayadi M, AlFaris M, Yahya M. Concise anti-oxidative stress defense effects of Duvalia corderoyi in the liver and kidney tissues of streptozotocin-induced diabetic rats. Journal of Taibah University for Science. 2020;14(1):524-33. DOI: 10.1080/16583655.2020.1751962

11. Alfonso S, González A, Morales D, Mora M, López L. Sistema de monitoreo de glucosa en sangre suma sensor sxt: Su control y certificación de la calidad. Convención Internacional de Salud Pública Cuba Salud 2012; La Habana, Cuba 2012. p. 10.

12. Institute of isotopes Ltd. Insulina IRMA kit. Budapest: IZOTOP; 2018. p. 2.

13. Hisakazu M. Determination of nitrate in biological fluids using nitrate reductase in a flow system. J Health Sci. 2001;47(1):65-7. DOI: 10.1248/jhs.47.65

14. Beutler E. Improved assay of the enzymes of glutathione synthesis. Clin Chim Acta. 1986;158(1):115-23. DOI: 10.1016/0009-8981(86)90122-1

15. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malondialdehyde and 4-hydroxynonenal. Methods Enzymol. 1990;186:407-21. DOI: 10.1016/0076-6879(90)86134-H

16. Kalousavá M, Skrha J, Zima T. Advanced glycation end-products and advanced oxidation protein products in patients with Diabetes Mellitus. Physiol Res. 2002;51(6):597-604.

17. National Institute of Health. Guide for the Care and Use of Laboratory Animals Washington D. C.: National Academies Press; 2011.

18. Bonner-Weir S, Trent DF, Honey RN, Weir GC. Responses of neonatal rat islets to streptozotocin: limited B-cell regeneration and hyperglycemia. Diabetes. 1981;30(1):64-9. DOI: 10.2337/diabetes.30.1.64

19. Portha B, Levacher C, Picon L, Rosselin G. Diabetogenic effect of streptozotocin in the rat during the perinatal period. Diabetes. 1974;23(11):889-95. DOI: 10.2337/diab.23.11.889

20. Patil M, Suryanarayana P, Putcha U, Srinivas M, Reddy G. Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract. Oxidative Medicine and Cellular Longevity. 2014:1-10. DOI: 10.1155/2014/463264

21. Galassi P, Gullace F. Reproducción en Animales de Laboratorio. Buenos Aires: Facultad de Ciencias Veterinarias; 2014. 22 p.

22. Busineni G, Dwarakanath V, Chikka BK. Streptozotocin. A Diabetogenic Agent in Animal Models. Int J Pharm Pharm Res. 2015;3(1):253-69.

23. Noguchi G, Huising M. Integrating the inputs that shape pancreatic islet hormone release. Nature Metabolism. 2019;1:1189-201. DOI: 10.1038/s42255-019-0148-2

24. Dos-Santos J, Tewari S, Mendes R. The Role of Oxidative Stress in the Development of Diabetes Mellitus and Its Complications. Journal of Diabetes Research. 2019;2019:1-3. DOI: 10.1155/2019/4189813

25. Zhang P, Li T, Wu X, Nice EC, Huang C, Zhang Y. Oxidative stress and diabetes: antioxidative strategies. Frontiers of Medicine. 2020:1-18. DOI: 10.1007/s11684-019-0729-1

26. Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. Journal of Diabetes & Metabolic Disorders. 2013;12(60):1-7. DOI: 10.1186/2251-6581-12-60

27. Bodnarchuk YV. Age features of the morpho-functional state of the liver in the distant terms of experimental diabetes mellitus. Morphologia. 2018;12(3):24-30. DOI: 10.26641/1997-9665.2018.3.24-30

28. Galina M, Ortiz M, Guerreo M. Estrés oxidativo y antioxidantes. Avances en investigación agropecuaria. 2018;22(1):47-61.

29. Ighodaro OM. Molecular pathways associated with oxidative stress in diabetes mellitus. Biomedicine & Pharmacotherapy. 2018;108:656-62. DOI: 10.1016/j.biopha.2018.09.05

30. Alhasawi A, Legendre F, Jagadeesan S, Appanna V, Appanna V. Biochemical Strategies to Counter Nitrosative Stress: Nanofactories for Value-Added Products. Molecular Tools in Microbial Diversity: Elsevier; 2019 p. 153-17.

31. Visiedo F, Santos-Rosendo C, Mateos-Bernal R, Gil-Sánchez M, Bugatto F, Aguilar-Diosdado M, et al. Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus. Oxidative Medicine and Cellular Longevity. 2017;2017:1-10. DOI: 10.1155/2017/5629341

32. Álvarez A, Béquer L, Gómez T, Molina JL, Lavastida M, Clapés S. Daño renal por hiperglucemias moderadas en un modelo animal de diabetes. Medicent Electrón. 2017;21(1):46-56.

33. Gómez T, Bequer L, Sánchez C, de la Barca M, Muro I, Reyes MA, et al. Inducción neonatal de hiperglucemias moderadas: indicadores metabólicos y de estrés oxidativo en ratas adultas. Rev ALAD. 2014;4(4):148-57.

34. Gómez T, Bequer L, Mollineda A, Molina J, Álvarez A, Lavastida M, et al. Concentration of Zinc, Copper, Iron, Calcium, and Magnesium in the Serum, Tissues, and Urine of Streptozotocin-Induced Mild Diabetic Rat Model. Biol Trace Elem Res 2017;179:237-46. DOI: 10.1007/s12011-017-0962-x

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Published

2021-10-27

How to Cite

1.
Bequer Mendoza L, Quintero M, Gómez T, Guerra I, Molina JL, Freire C, et al. Effects of neonatal injection of streptozotocin on biochemical indicators and oxidative stress in rats. Rev Cubana Inv Bioméd [Internet]. 2021 Oct. 27 [cited 2025 Aug. 1];40(3). Available from: https://revibiomedica.sld.cu/index.php/ibi/article/view/804

Issue

Vol. 40 No. 3 (2021): Julio-Septiembre

Section

ARTÍCULOS ORIGINALES

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