MOTILIPERM Ameliorates Immobilization Stress-Induced Testicular Dysfunction via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway in SD Rats

Abstract

<jats:p>It is well established that physiological stress has an adverse effect on the male reproductive system. Experimental studies have demonstrated the promising effects of MOTILIPERM in male infertility. MOTILIPERM extract is composed of three crude medicinal herbs: Morinda officinalis How (Rubiaceae) roots, Allium cepa L. (Liliaceae) outer scales, and Cuscuta chinensis Lamark (convolvulaceae) seeds. The present study aimed to investigate the possible mechanisms responsible for the effects of MOTILIPERM on testicular dysfunction induced by immobilization stress. Fifty male Sprague Dawley rats were divided into five groups (10 rats each): a normal control group (CTR), a control group administered MOTILIPERM 200 mg/kg (M 200), an immobilization-induced stress control group (S), an immobilization-induced stress group administered MOTILIPERM 100 mg/kg (S + M 100), and MOTILIPERM 200 mg/kg (S + M 200). Stressed rats (n = 30) were subjected to stress by immobilization for 6 h by placing them in a Perspex restraint cage, while controls (n = 20) were maintained without disturbance. Rats were administrated 100 or 200 mg/kg MOTILIPERM once daily for 30 days 1 h prior to immobilization. At the end of the treatment period, we measured body and reproductive organ weight; sperm parameters; histopathological damage; reproductive hormone levels; steroidogenic acute regulatory protein (StAR); biomarkers of oxidative stress; and apoptosis markers. MOTILIPERM treatment improved testicular dysfunction by up-regulating (p &lt; 0.05) sperm count, sperm motility, serum testosterone level, StAR protein level, Johnsen score, and spermatogenic cell density in stressed rats. MOTILIPERM decreased oxidative stress by increasing (p &lt; 0.05) testicular superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione peroxidase-4 (GPx 4), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) levels and decreasing (p &lt; 0.05) malondialdehyde (MDA) and reactive oxygen species/reactive nitrogen species (ROS/RNS) levels. Furthermore, MOTILIPERM down-regulated (p &lt; 0.05) cleaved caspase 3 and BCL2 associated X protein (Bax) levels; increased pro caspase-3 and B-cell lymphoma 2 (Bcl-2) levels; and upregulated testicular germ cell proliferation in stressed rats. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels also significantly (p &lt; 0.05) decreased after pretreatment with MOTILIPERM in stressed rats. Collectively, our results suggest that, in immobilization-mediated stress-induced testicular dysfunction, MOTILIPERM sustains normal spermatogenesis via antioxidant and anti-apoptotic activities by activating the NRF/HO-1 signaling pathway.</jats:p>

Andrological Aspects of Exercise: Moderate Swimming Protects against Isoproterenol Induced Testis and Semen Abnormalities in Rats

“…Our findings regarding the negative effects of oxidative stress on the male reproductive system are in line with several studies indicating that oxidative stress causes testicular dysfunction. These studies also suggest that oxidative stress in the testicular milieu is associated with DNA damage and abnormal sperm production, accounting for the rising prevalence of reduced male fertility [16][17][18]. Moreover, oxidative stress factors are reported to play a causal role in the development of sperm abnormalities and abnormal function of the testes [19,20].…”

5-fluorouracil and Rumex obtusifolius extract combination trigger A549 cancer cell apoptosis: uncovering PI3K/Akt inhibition by in vitro and in silico approaches

“…Many factors can damage DNA, proteins, or lipids in cells directly or indirectly, such as exogenous drugs, endogenous reactive oxygen species, or free radicals. During this process, the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered a significant modulator, maintaining the cellular redox balance by expressing antioxidant proteins 24,25 . Several cancer chemopreventive compounds targeting Nrf2 have been reported, such as Oltipraz, Sulforaphane, Curcumin, Resveratrol, and Luteolin 24 .…”

Gui-A-Gra Attenuates Testicular Dysfunction in Varicocele-Induced Rats via Oxidative Stress, ER Stress and Mitochondrial Apoptosis Pathway

“…Epididymal and vas deference sperm count and sperm motility were evaluated as described previously [45]. In brief, the distal cauda and the vas deference were rapidly washed in PBS to remove excess blood and placed in separate microcentrifuge tubes containing pre-warmed normal saline at 37 • C. Tissues were gently cut with anatomic scissors and sperm were allowed to suspend for 5 min.…”

“…At least thirty seminiferous tubules (STs) per section were randomly examined under a light microscope (400×). Each section was evaluated using Johnsen's score [45]. Similarly, at least 30 STs were analyzed for spermatogenic cell density by measuring the diameter of the ST and the thickness of the germinal cell layer using the formula of (diameter of the ST / thickness of the germinal cell layer).…”