Abstract
Paroxetine is often used to treat patients with psychotic disorders, one of the side effects of this medication is that it causes erectile dysfunction in such individuals. There is a little or no information on the effect of paroxetine on some biochemical and endothelial markers of experimental models, hence the need for this research. Biochemical and endothelial functional makers in male Wistar rats were evaluated after oral administration of paroxetine for 4, 7, 21, 28 and 35 days. Seventy-two (72) male Wistar rats were grouped into two of thirty-six rats in group A (control) which received normal saline and thirty-six rats in group B (paroxetine-treated) which received 10 mg/Kg body weight of paroxetine hydrochloride for 4, 7, 14, 21, 28, and 35days respectively. During this period, six animals from the two groups were sacrificed on days 4,7,14, 21, 28 and 35 by anaesthesia using diethyl ether, blood was collected into lithium–heparinized bottles and the tissues of interest (penile and heart) of the rats were excised and preserved in ice-cold sucrose-tris buffer. Phosphodiesterase 5, arginase, nitric oxide were evaluated from the isolated tissue homogenates while cGMP, endothelin-1, creatine kinase, lipid profile and testosterone concentrations were evaluated from the plasma. The results revealed that during pre-treatment with paroxetine, there was significant (p < 0.05) 85.19 ± 4.64 and 92.58 ± 0.57 respectively PDE 5 inhibition in the penile and cardiac homogenates of rats. Nitric oxide concentration was significantly (p> 0.05) 2.96 ± 0.27 and 4.82 ± 0.05reduced while arginase activities increased significantly (p > 0.05) 272.16 ± 5.07 and 201.93 ± 11.82 during paroxetine treatment. Same trend of results were observed with plasma endothelin-1 concentration (12.88 ± 0.78), cGMP concentration (0.14 ± 0.00) and Testosterone concentration (0.46 ± 0.03) was significantly (p > 0.05) decreased during paroxetine-treatment. However, plasma creatine kinase 463.6 ± 50.96, triacyl glycerol 58.61 ± 5.49, total cholesterol 181.55 ± 9.72 and low-density lipoprotein cholesterol 165.86 ± 9.72 were significantly (p < 0.05) increased during paroxetine-treatment. However, no significant (p > 0.05) difference was observed in the high-density lipoprotein cholesterol 8.07 ± 0.46 during administration with paroxetine. From this study, it can be concluded that paroxetine administration altered erectile and endothelial markers throughout the period of administration and as such should be prescribed to patients with caution.
Highlights
Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine are effective in treating psychological disorders and are the most commonly prescribed first-line oral therapy
Louis, United States of America; Imidazole (Lot no.:B0212) was a product of Santa Cruz Biotechnology, Dallas, Texas; Sildenafil citrate (Lot no.: A471719) was a product of Pfizer, New York; Paroxetine hydrochloride (Lot no.: 615M) was a product of Glaxo Smith Klein (GSK), Brasov, Romania; Tween-80 was a product of BDH Laboratory Chemicals, Poole, England; L-arginine was a product of Burgoyne Burbidges & Co., Mumbai, India; Assay kit for testosterone was a product of Monobind Inc., Lake Forest, USA; Assay kits for cyclic guanosine monophosphate (cGMP) (Lot no.: P104126) and Endothelin-1 (P109997) were products of Biotechne Ltd, Abingdon, United Kingdom; Assay kits for creatine kinase, total cholesterol, triglyceride, low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC) were products of Randox laboratories Co-Artrim, United Kingdom
The elevated activity of cardiac PDE 5 persisted for two weeks after the administration of paroxetine was discontinued and the values determined on day 28 or 35 were not significantly (p < 0.05) different from those of day 21
Summary
Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine are effective in treating psychological disorders and are the most commonly prescribed first-line oral therapy. Their clinical usefulness is often limited by poor observance and discontinuation due to lack of therapeutic response and possibly adverse effects such as causing male sexual disorders (Nantz et al, 2009). One of the adverse effects of SSRIs administration to psychotic patients is erectile dysfunction and symptoms of sexual dysfunction have been reported to persist after discontinuation of SSRIs (Simonsen et al, 2016) It delays orgasm/sex drive and inhibits synthesis of nitric oxide in male rats (Prabhakar and Richard, 2010). There is little or no information on the effects of paroxetine administration on endothelial parameters especially cGMP and endothelin-1 concentrations in experimental animals, the justification of this study
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
