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

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.

Quercetin Reverses Altered Energy Metabolism in the Heart of Rats Receiving Adriamycin Chemotherapy.

The primary aim of this study was to find the potential modulatory roles of quercetin (QUE) against Adriamycin (ADR)-induced cardiotoxicity. A total of 50 rats were assigned to five groups: a control group, an ADR-treated group, a QUE-treated group, a prophylaxis-cotreated group, and a therapeutic-cotreated group, respectively. QUE exhibited a significant cardioprotective effect, particularly, when it was administered prior to and concurrently with ADR treatment (prophylaxis-cotreated group). This effect was biochemically evident by the significant decreases in the serum levels of myocardial injury biomarkers such as troponin, creatine kinase-myocardium bound, and creatine phosphokinase. In addition, significant elevations in myocardial antioxidant indices coupled with significant reductions in myocardial malondialdehyde contents and DNA damage, elicited by ADR injection, were observed. All these biochemical improvements were accompanied by a significant histopathological recovery and obvious modulation of the AMP-activated protein kinase (AMPK) signaling pathway by promoting the expression of the AMPKα2, PPARα, and PCG-1α genes. Taken together, these findings conclusively showed that QUE administration through its antioxidant capacity and myocardial energy metabolism restoration provides a prophylactic effect in response to ADR-induced deleterious effects, in the rat heart.