Isoliquiritigenin ameliorates paroxetine-induced sexual dysfunction in male albino mice.

Paroxetine (PRX), a widely prescribed antidepressant, often leads to sexual dysfunction. The available management options such as sildenafil (SDF), are associated with side effects. The present study investigates the fertility-boosting properties of isoliquiritigenin (ISL) on PRX-induced sexual dysfunction in male mice. We allocated fertile mice into six different groups (n = 5): group I- DMSO; group II- PRX; group III- co-administered PRX and SDF; group IV- ISL alone; group V- co-administered PRX and ISL (low dose); and, group VI- co-administered PRX and ISL (high dose). 14 days post treatment, animals were sacrificed, and the weights of the testis and epididymis were evaluated. Furthermore, sperm parameters, testicular and epididymal antioxidant levels, serum testosterone and nitric oxide (NO) levels, histoarchitecture of testis and epididymis, and markers of cellular toxicity were assessed. Results revealed that the PRX administration reduced organ weights, sperm count, intact acrosome, catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), serum testosterone, and NO levels, and increased sperm abnormalities and MDA levels (a biomarker for lipid peroxidation). Additionally, we observed damage in the testis and epididymis. The toxicity biomarker study revealed a higher concentration of SGOT, SGPT, and ALP enzymes in the PRX-treated group. However, the co-administration of PRX with ISL ameliorated the adverse effect of PRX on the parameters mentioned above. The PRX+ISL (high) results were almost at par with the PRX+SDF group. The group that received ISL alone showed overall improvements. In conclusion, our comprehensive panel of tests indicates that ISL could be helpful in managing sexual dysfunction.

Orange peels modulate antioxidant markers and key enzymes relevant to erection in the penile tissue of paroxetine-treated rats.

In comparison to other antidepressant drugs, erectile dysfunction (ED) is more pronounced in paroxetine use. On the other hand, orange (Citrus sinensis) peels commonly consumed in various forms are used in folkloric medicine for ED management. Thus, this study evaluated the effect of orange peels infusion on sexual behaviour, nitric oxide (NO) level and some enzymes (arginase, phosphodiesterase-5 [PDE-5], acetylcholinesterase [AChE] and adenosine deaminase [ADA]) in paroxetine-treated rats. Erectile dysfunction was induced with paroxetine (10 mg/kg body weight). The animals were grouped into five (n = 6): normal rats; paroxetine-induced rats; paroxetine-induced rats treated with sildenafil citrate (5 mg/kg); paroxetine-induced rats treated with orange peels infusion (50 mg/kg); Paroxetine induced rats treated with orange peel infusions (100 mg/kg). The results revealed a significant decrease in sexual behaviour, NO level and the activities of antioxidant enzymes, while there was a significant increase in arginase, PDE-5, AChE and ADA activities in paroxetine-induced rats. However, orange peel infusions ameliorated erectile dysfunction in paroxetine-treated rats. This study showed some possible biochemical basis underlying the use of orange peels infusion in erectile dysfunction management.

DA-8159 reverses selective serotonin reuptake inhibitor-induced erectile dysfunction in rats.

OBJECTIVES: To assess the efficacy of the phosphodiesterase 5 inhibitor, DA-8159, in selective serotonin reuptake inhibitor (SSRI)-induced rat erectile dysfunction model by measuring intracavernous pressure (ICP). METHODS: Erectile dysfunction was induced by oral administration of either paroxetine or fluoxetine in rats. The changes in ICP and mean arterial pressure (MAP) were simultaneously recorded throughout electrostimulation of the cavernous nerve with 2 or 10 Hz after intravenous injection of DA-8159 (1 mg/kg). Statistical analysis was performed on the ICP/MAP ratio and the area under the curve of the ICP/MAP ratio. RESULTS: Although the reduction in the ICP responses after acute paroxetine or fluoxetine administration was statistically significant, the electrical stimulation of the cavernous nerve induced a statistically significant, frequency-dependent increase in the ICP/MAP ratio after DA-8159 administration. The differences in the ICP/MAP ratio and corresponding area under the curve values from the SSRI-treated group were statistically significant. CONCLUSIONS: The results of the present study have demonstrated that DA-8159 reverses the decrease in ICP induced by SSRI treatment, suggesting that DA-8159 may be a potential therapeutic agent for the treatment of erectile dysfunction associated with the use of SSRIs.

The toxicity profile of a single dose of paroxetine: an alternative approach to acute toxicity testing in the rat.

In this study we have examined the effect of a single administration of the selective serotonin reuptake inhibitor, paroxetine (120-300 mg kg(-1), orally) in a recently developed rodent model of acute toxicity testing. Reduced body-weight, food consumption, water consumption and body temperature were observed in all paroxetine-treated groups, which were reversible within 7 days. Five days after administration, a dose-dependent increase in red blood cells, haemoglobin and haematocrit was observed with the 3 higher dose levels of paroxetine, which was significant in the 240 and 300 mg kg(-1) treatment groups (P < 0.05). Hyperactivity was apparent in the first 24 hr following treatment, as was evidence of the serotonin syndrome. When the animals were sacrificed (11 days after drug administration), an increase in liver weight was observed in the highest dose. These results are in agreement with those previously observed with paroxetine at the preclinical and clinical levels. They demonstrate that this rodent model, because of its multi-parameter nature, is a useful method for examining the consequences of a single high dose of an antidepressant drug.