The aim of the present study was to determine the effect of sildenafil on dopamine, 5-hydroxyindol acetic acid (5-HIAA) and selected biomarkers of oxidative stress in the brain of hypoglycemic rats. The animals were treated intraperitoneally as follows: group 1 (control), saline solution; group 2, insulin (10 U per rat or 50 U kg−1); group 3, insulin + single dose of sildenafil (50 U kg−1 + 50 mg kg–1); group 4, insulin + three doses of sildenafil every 24 hours (50 U kg−1 + 50 mg kg−1). In groups 2, 3 and 4, insulin was administered every 24 hours for 10 days. Blood glucose was measured after the last treatment. On the last day of the treatment, the animals´ brains were extracted to measure the levels of oxidative stress markers [H2O2, Ca2+,Mg2+-ATPase, glutathione and lipid peroxidation (TBARS)], dopamine and 5-HIAA in the cortex, striatum and cerebellum/medulla oblongata by validated methods. The results suggest that administration of insulin in combination with sildenafil induces hypoglycemia and hypotension, enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines. Administration of insulin and sildenafil promotes biometabolic responses in glucose control, namely, it induces hypoglycemia and hypotension. It also enhances oxidative damage and provokes changes in the brain metabolism of biogenic amines.
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1. A. V. Raveendran E. C. Chacko and J. M. Pappachan Non-pharmacological treatment options in the management of diabetes mellitus Eur. Endocrinol.14 (2018) 31–39; https://doi.org/10.17925/EE.2018.14.2.31
2. A. Hussain O. B. Latiwesh F. Ali M. Y. G. Younis and J. A. Alammari Effects of body mass index glycemic control and hypoglycemic drugs on serum uric acid levels in type 2 diabetic patients Cureus10 (2018) e3158; https://doi.org/10.7759/cureus.3158
3. G. T. Chen B. B. Yang J. H. Chen Z. Zhang L. L. Zhu H. S. Jiang W. Yu Y. Chen and Y. T. Dai Pancreatic kininogenase improves erectile function in streptozotocin-induced type 2 diabetic rats with erectile dysfunction Asian J. Androl.20 (2018) 448–453; https://doi.org/10.4103/aja.aja_23_18
4. L. Chen S. E. Staubli M. P. Schneider A. G. Kessels S. Ivic L. M. Bachmann and T. M. Kessler Phosphodiesterase 5 inhibitors for the treatment of erectile dysfunction: a trade-off network meta-analysis Eur. Urol.68 (2015) 674–680; https://doi.org/10.1016/j.eururo.2015.03.031
5. R. S. Calabrò G. Polimeni and P. Bramanti Current and future therapies of erectile dysfunction in neurological disorders Rec. Pat. CNS Drug Discov.6 (2011) 48–64.
6. S. J. Flora Role of free radicals and antioxidants in health and disease Cell. Mol. Biol.53 (2007) 1–2.
7. J. T. Coyle and P. Puttfarcken Oxidative stress glutamate and neurodegenerative disorders Science262 (1993) 689–695.
8. M. C. Vogt and J. C. Brüning CNS insulin signaling in the control of energy homeostasis and glucose metabolism – from embryo to old age Trends Endocrinol. Metab. 24 (2013) 76–84; https://doi.org/10.1016/j.tem.2012.11.004
9. G. D. Calderon N. Osnaya Brizuela M. Ortiz Herrera O. H. Juarez A. Valenzuela Peraza and G. Barragan Mejía Effect of an antiviral and vitamins A C D on dopamine and some oxidative stress markers in rat brain exposed to ozone Arch. Biol. Sci. Belgrade65 (2013) 1371–1379; https://doi.org/10.1186/s12868-018-0474-4
10. D. Calderón Guzmán N. Osnaya Brizuela M. Ortíz Herrera E. Hernandez Garcia G. Barragan Mejía H. Juarez Olguín A. Valenzuela Peraza J. Attilus and N. Labra Ruiz Effect of cerebrolysin on dopaminergic neurodegeneration of rat with oxidative stress induced by 3-nitropropionic acid Acta Pharm. 66 (2016) 443–448; https://doi.org/10.1515/acph-2016-0027
11. F. Bilotta and G. Rosa Optimal glycemic control in neurocritical care patients Crit. Care16 (2012) 163–165; https://doi.org/10.1186/cc11521
12. S. Ammon-Treiber D. Stolze H. Schroder H. Loh and V. Hollt Effects of opioid antagonists and morphine in a hippocampal hypoxia/hypoglycemia model Neuropharmacology49 (2005) 1160–1169; https://doi.org/10.1016/j.neuropharm.2005.06.016
13. J. H. Jhamandas K. H. Harris T. Petrov and K. H. Jhamandas Activation of nitric oxide-synthesizing neurons during precipitated morphine withdrawal Neuroreport7 (1996) 2843–2846.
14. G. D. Calderón G. E. Hernández M. G. Barragán O. H. Juárez G. J. Saldivar and R. N. Labra Effect of morphine and lacosamide on levels of dopamine and 5-HIAA in brain regions of rats with induced hypoglycemia Pak. J. Biol. Sci. 17 (2014) 292–296.
15. S. P. Filippov ATPase activity of rat brain microsomal and synaptosomal fractions in insulin hypoglycemia and its treatment with glucose Probl. Endokrinol. (Moskow) 37 (1991) 52–54; https://doi.org/10.1134/S0022093006020062
16. E. Mandosi E. Giannetta T. Filardi M. Lococo C. Bertolini M. FAllarino D. Gianfrilli M. A. Venneri L. Lenti S. Morano and A. Lenzi Endothelial dysfuntion markers as a therapeutic target for sildenafil treatment and effects on metabolic control in type 2 diabetes Expert Opin. Ther. Target. 19 (2015) 1617–1622; https://doi.org/10.1517/14728222.2015.1066337
17. C. E. Ramirez H. Nian Y. Chang L. J. Gamboa J. M. Luther N. J. Brown and C. A. Shibao Treatment with sildenafil improves insulin sensitivity in prediabetes: a randomized controlled trial JCEM100 (2015) 4533–4540; https://doi.org/10.1210/jc.2015-3415
18. F. G. Al-Amran A. A. Zwain N. R. Hadi and A. M. Al-Mudhaffer Autonomic cerebral vascular response to sildenafil in diabetic patient Diabetol. Metab. Syndr.4 (2012) 2–8; https://doi.org/10.1186/1758-5996-4-2