Sildenafil alters biogenic amines and increases oxidative damage in brain regions of insulin-hypoglycemic rats

Abstract

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.

Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment

“…Moreover, hyperinsulinemic animals displayed a significant increase in the concentration of 5-hydroxyindoleacetic acid (5-HIAA) (Hedges’ g = 0.40; 95% C.I. = 0.12, 0.68; p = 0.005; I 2 = 75.62%; based on 64 comparisons from 17 studies [ 62 , 63 , 65 , 68 , 72 , 73 , 75 , 76 , 108 – 116 ]) and Trp accumulation (Hedges’ g = 2.22; 95% C.I. = 1.39, 3.05; p < 0.001; I 2 = 41.79%; based on one ex vivo study [ 63 ] fetching five comparisons).…”

“…95% C.I. = −0.77, −0.01; p = 0.043; I 2 = 82.47%; based on 68 comparisons from 15 studies[62][63][64][65][66][67][68][69][70][71][72][73][74][75][76]) that was mirrored by an increase (Hedges'g = 0.87, 95% C.I. = 0.05, 1.69; p = 0.037; I 2 = 44.29%; based on two studies[77,78] fetching three comparisons) in brain insulinresistant animals.…”