Protective Effects of Chromolaena odorata on Oxidative Stress Biomarkers and Penile Histoarchitecture in Paroxetine-Induced Erectile Dysfunction

Abstract

Paroxetine is the most serotonergically active SSRI, and is linked to the most severe degree of sexual dysfunction, such as erectile dysfunction (ED) occurring in 30–70% of male patients. It works through inhibition of neuronal and endothelial nitric oxide synthase (nNOS/eNOS), inhibition of NO-cGMP signalling pathway, serotonin-dopamine antagonism, hormonal dysregulations and inducing oxidative stress. Chromolaena odorata (L.) The medicinal plant R.M. King & H. Robinson (Asteraceae) has been well documented with antioxidants, anti-inflammatory, vasorelaxant and cytoprotective properties due to its flavonoids and phenolic acids. The protective effects against paroxetine-induced penile oxidative stress and histoarchitectural injury have not been studied. The protective effect of ethanolic leaf extract of C. odorata on oxidative stress biomarkers malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) and penile histoarchitecture was therefore evaluated in an ED model caused by paroxetine in adult male Wistar rats. Twenty rats (180–220 g) were randomly divided into four groups (n = 4), namely: Control (distilled water), Paroxetine only (10 mg/kg), Paroxetine + low-dose of C. odorata (100 mg/kg), and Paroxetine + high-dose of C. odorata (200 mg/kg). All the treatments were given for 28 days orally continuously. Paroxetine administration reduced SOD activity (0.0757 ± 0.0048 U/mg vs. 0.1011 ± 0.0106 U/mg in controls) and CAT activity (1.433 ± 0.0923 vs. 2.331 ± 0.4225 U/mg), and elevated MDA levels (0.7830 ± 0.0380 µM vs. 0.6483 ± 0.0041 µM). The co-administration of low doses of C. odorata significantly increased GSH (0.6343 ± 0.0657 mM) when compared to all the other groups (p < 0.05). The highest was observed in the low dose group (1.139 ± 0.2090 µM), potentially due to pro-oxidant activity of polyphenolic compounds with concentration. Cavernosal disorganisation, eosinophilic fibrosis, and compression of the sinusoidal spaces in penile tissue were the most significant histopathologic findings in penile tissue following paroxetine treatment, whereas neuropil vacuolation and pyknotic neuronal nuclei were the most significant neuropathologic findings in brain tissue. Both doses of C. odorata extract reduced these alterations, with the highest dose showing most complete structural restoration, in the form of well-defined deeply folded mucosal architecture, relaxed and organised smooth muscle stroma, and consolidated neuropil with good neuronal morphology. The present findings suggest a dose-dependent cytoprotective activity against paroxetine-induced penile and neural tissue injury of C. odorata which underscores its potential further investigation as a candidate herbal therapeutic agent for SSRI-associated erectile dysfunction, mainly at the histological level.