Long-term sildenafil citrate administration induces oxidative stress and changes in nissl substance in adult male Wistar rats

Abstract

Viagra (sildenafil) treats erectile dysfunction by inhibiting PDE5, which increases blood flow. Excessive use can disrupt nitric oxide signaling, leading to neurotoxicity and oxidative stress. This raises concerns about potential long-term effects on brain health. The aim of this study was to evaluate the long-term effects of sildenafil citrate on oxidative stress and changes in nissl substance in the
hippocampus of adult male Wistar rats. The study involved a control group and three experimental groups, each consisting of six rats. The rats were treated with sildenafil citrate dissolved in distilled water. Group 1 received 2 ml/kg distilled water orally once every two days for 8 weeks. Groups 2, 3 and 4 received sildenafil citrate at doses of 4.5 mg/kg, 9 mg/kg and 13.5 mg/kg orally once every two days for 8 weeks. Catalase (CAT), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) concentrations in the brain were measured spectrophotometrically. Hippocampus Nissl substance staining intensity was determined using cresyl fast violet stain. The results showed no significant changes in MDA and GSH levels in brain tissue. However, in group IV
(13.5 mg/kg sildenafil citrate), rats exhibited a significant decrease in brain SOD levels. Similarly, CAT activity decreased significantly in group IV compared to the control group and group II (4.5 mg/kg sildenafil citrate). NO levels remained unchanged in all treatment groups. There was no significant difference in nissl substance staining intensity for the groups that received 4.5 mg/kg and 9 mg/kg of
viagra compared to the control group. However, the group that received 13.5 mg/kg of viagra showed a significant decrease in nissl substance compared to the control group. Collectively, these results suggest that while low to moderate doses of sildenafil citrate do not adversely affect hippocampal oxidative status or neuronal integrity, prolonged exposure to high doses may impair antioxidant enzyme activities and induce subtle neuronal alterations. This study highlights the importance of dose considerations in the
chronic use of sildenafil and highlights potential neurotoxic risks associated with its high-dose administration.