Comparative effect of administration and discontinuation of sildenafil and/or clomipramine on the hepatic, cardiac and testicular tissues of male rats

Abstract

In this study, we examined the adverse consequences of prolonged treatment with sildenafil and/or clomipramine (CLO) on the hepatic, cardiac and testicular tissues of rats. Additionally, we investigated the potential effects of treatment discontinuation. To this end, 60 adult male rats were randomly assigned into six groups and were orally treated with 4.5 mg sildenafil /kg BW (SLD) and 9 mg/ kg BW (SHD), 2.25 mg CLO/kg BW (CLO), 4.5 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SLD‐CLO) and 9 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SHD‐CLO) while the control rats received 0.5 ml distilled water for 8 weeks. Then, five rats from each group were sacrificed and the other five rats were left untreated for another four weeks to recover from the drug treatment. Long‐term administration of sildenafil and/or CLO led to oxidative stress, inflammation and structural changes in the liver, heart and testis, reduction in sperm count and motility, an increase in abnormalities, and a reduction in serum testosterone, FSH and LH levels. All tested parameters returned to the normal state following the four‐week discontinuation of sildenafil. Additionally, all the alterations caused by long‐term administration of CLO, SLD‐CLO and SHD‐CLO were significantly improved during the recovery period.

EFFECTS OF SILDENAFIL ON THE TESTES OF THE NONDIABETIC AND DIABETIC ADULT ALBINO RATS (Light and Electron Microscopic Study)

“…In the present study, the histological examination of testicular sections from the non-diabetic group treated with high-dose sildenafil (13.5 mg) showed thickened tunica albuginea with mild sub-capsular edema, slightly distorted tubules with tunica propria, slightly diminished germinal lining and nearly complete spermatogenic layers in most of tubules, and normal interstitium with Leydig cells. These results were in agreement with Al-Fartosi 12 ; Alp et al 13 ; and El-Sheikh et al 14 who reported that most of tubules had normal architecture with some tubules had decreased germinal lining.…”

Gastroprotective, hepatoprotective, and nephroprotective effects of thymol against the adverse effects of acetylsalicylic acid in rats: Biochemical and histopathological studies

“…Inflammation and oxidative stress are involved in the pathophysiology of nephrotoxicity and hepatotoxicity induced by many drugs ( Edrees et al, 2018 , El‐Sheikh et al, 2021a , El-Sheikh et al, 2021b ). Our results indicate that ASA treatment-induced inflammation and oxidant/antioxidant imbalance, which was manifested by a significant elevation of serum TNF-α (pro-inflammatory cytokine), MPO (A vital mechanistic link between inflammation and oxidation) ( Mostafa et al, 2018 ), MDA (lipid peroxidation biomarker) concentration as well as a significant reduction in GSH levels (non-enzymatic antioxidant), SOD and GPx activities (enzymatic antioxidant).…”

“…The rats were fasted overnight at the end of the study (10 days). They were weighed and sedated via intramuscular injection with a xylazine (5 mg/kg) and ketamine HCl (50 mg/kg) mixture ( El‐Sheikh et al, 2021a , El-Sheikh et al, 2021b ). A fine sterilized glass capillary tube was used to puncture the retroorbital venous plexus and collect blood samples.…”

Sildenafil Citrate Induces Prostatic Hyperplasia in BPH Model Rats and Aged Rats

“…A large number of studies have shown the association between prolonged sildena l citrate utilization and the induction of oxidative stress, in ammatory responses, and structural changes within the testicular milieu. This long-term exposure has been linked to diminished sperm count and motility, elevated serum levels of testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), as well as an escalated risk of penile brosis, culminating in irreversible damage to the corpus cavernosum tissue [25][26][27][28][29][30] .…”