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.
Pharmacokinetics Doxycycline dose HPLC African catfish (Clarias gariepinus) aquaculture has experienced widespread production and has lately gained considerable interest in Egypt. Doxycycline (DOX) is used to control certain common fish's bacterial diseases, such as Septicemia, Fin rot, Columnaris, and Tail Rot. Therefore, our experiment was conducted to assess the pharmacokinetic properties of single doxycycline dose (20 mg/kg BW) orally administered in the African catfish. DOX plasma levels were measured using HPLC with a limit of detection nearly 0.035 µg/ ml, and then were undergoing compartmental analysis; a onecompartment model was detected. The doubled-peak phenomenon was identified after oral administration and the 1 st peak concentration (C max1) and the 2 nd peak concentration (C max2) in plasma were 2.29±0.46 and 1.68±0.33µg/mL at 1 st and 8 th h respectively, the absorption half-life (t 1/2ka) was 0.045 h, the elimination half-life (t 1/2ke) was 5.81 h, systemic total body clearance (Cl) was 0.72 mL/h/kg, volume of distribution of the central compartment (V d /F) was 5.74±1.11 L. These findings suggested that DOX was to some extent rapidly absorbed, widely distributed, and slowly excreted; moreover, it could be subjected to enterohepatic recycling.
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