Dataset Information

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

ABSTRACT: 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 < 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 < 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 < 0.05) malondialdehyde (MDA) and reactive oxygen species/reactive nitrogen species (ROS/RNS) levels. Furthermore, MOTILIPERM down-regulated (p < 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 < 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.

SUBMITTER: Karna KK

PROVIDER: S-EPMC7370033 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Karna Keshab Kumar KK Soni Kiran Kumar KK You Jae Hyung JH Choi Na Young NY Kim Hye Kyung HK Kim Chul Young CY Lee Sung Won SW Shin Yu Seob YS Park Jong Kwan JK

International journal of molecular sciences 20200703 13

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 ...[more]

PMID: 32635386

Similar Datasets

Project description:Testicular torsion carries the ominous prospect of inducing acute scrotal distress and the perilous consequence of testicular atrophy, necessitating immediate surgical intervention to reinstate vital testicular perfusion, notwithstanding the paradoxical detrimental impact of reperfusion. Although no drugs have secured approval for this urgent circumstance, antioxidants emerge as promising candidates. This study aspires to illustrate the influence of eprosartan, an AT1R antagonist, on testicular torsion in rats. Wistar albino rats were meticulously separated into five groups, (n = 6): sham group, eprosartan group, testicular torsion-detorsion (T/D) group, and two groups of T/D treated with two oral doses of eprosartan (30 or 60 mg/kg). Serum testosterone, sperm analysis and histopathological examination were done to evaluate spermatogenesis. Oxidative stress markers were assessed. Bax, BCL-2, SIRT1, Nrf2, HO-1 besides cleaved caspase-3 testicular contents were estimated using ELISA or qRT-PCR. As autophagy markers, SQSTM-1/p62, Beclin-1, mTOR and AMPK were investigated. Our findings highlight that eprosartan effectively improved serum testosterone levels, testicular weight, and sperm count/motility/viability, while mitigating histological irregularities and sperm abnormalities induced by T/D. This recovery in testicular function was underpinned by the activation of the cytoprotective SIRT1/Nrf2/HO-1 axis, which curtailed testicular oxidative stress, indicated by lowering the MDA content and increasing GSH content. In terms of apoptosis, eprosartan effectively countered apoptotic processes by decreasing cleaved caspase-3 content, suppressing Bax and stimulating Bcl-2 gene expression. Simultaneously, it reactivated impaired autophagy by increasing Beclin-1 expression, decreasing the expression of SQSTM-1/p62 and modulate the phosphorylation of AMPK and mTOR proteins. Eprosartan hold promise for managing testicular dysfunction arising from testicular torsion exerting antioxidant, pro-autophagic and anti-apoptotic effect via the activation of SIRT1/Nrf2/HO-1 as well as Beclin-1/AMPK/mTOR pathways.

Project description:ObjectiveTo investigate the therapeutic potential of dimethyl fumarate (DMF) in improving erectile function of bilateral cavernous nerve injury (BCNI) rats, along with elucidating its underlying mechanisms.MethodsA BCNI rat model was established by clamping bilateral cavernous nerve (CN). DMF was given by gavage at low (20 mg/kg/day) and high (40 mg/kg/day) dosages for a duration of 4 weeks. Erectile function was assessed by electrical stimulation of CN. Penis and CN tissues were collected for subsequent analysis. Additionally, PC-12 cell line was used to verify the mechanism of DMF in vitro. Nfe2l2 or Ho-1 gene knockdown PC-12 cell lines were constructed by lentiviral transfection, respectively. A damaged cell model was induced using H2O2. And then molecular biological methods were employed to analyze cellular molecules and proteins.ResultsDMF administration for 4 weeks led to improvements in erectile function, reduced fibrosis of penis corpus cavernosum in BCNI rats. The morphology of CN was improved and the number of nerve fibers increased. Furthermore, the levels of nNOS, NO, and cGMP were increased, while Ca2+ was decreased in penis corpus cavernosum. Notably, the levels of ROS, 3-NT and NLRP3 inflammasomes production were reduced, alongside increased expression of Nrf2 and HO-1 proteins in the dorsal penile nerve (DPN) and CN. In vitro, DMF increased cell viability, reduced ROS level, promoted SOD, diminished 3-NT, MDA and DNA damage markers, and inhibited the activation of NLRP3 inflammasomes in H2O2 induced PC-12 cells. Nfe2l2 knockdown and Ho-1 knockdown significantly attenuated the protective effect of DMF, respectively. Furthermore, inhibition of ROS production by N-acetylcysteine led to a reduction in NLRP3 inflammasome activation in H2O2 induced PC-12 cells.ConclusionsDMF improved erectile function of BCNI rats by protecting nerves through inhibiting oxidative stress and the activation of NLRP3 inflammasome-mediated pyroptosis via activation of Nrf2/HO-1 pathway.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets