Preliminary report on nitric oxide-mediated oxidative damage in adolescent varicocele

Romeo, Carmelo; Ientile, Riccardo; Impellizzeri, Pietro; Turiaco, Nunzio; Teletta, M.; Antonuccio, Pietro; Basile, Teresa Maria Altomare; Gentile, C

doi:10.1093/humrep/deg004

Cited by 72 publications

(55 citation statements)

References 34 publications

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“…In accordance with our observation, Vossen and De Smet (2015) (Vossen and De Smet, 2015) have shown that antioxidants can be used as therapy to decrease nitrite toxicity (AlGayyar et al, 2014;Al-Gayyar et al, 2016). Interestingly, NO has been connected to an elevation in lipid peroxidation and MDA in both humans (Romeo et al, 2003) and experimental rats (Özdamar et al, 2004). A rise in NO following eNOS overexpression has been connected to germ cell apoptosis in a cryptorchidism germ mouse model (i.e.…”

Section: Discussionsupporting

confidence: 82%

The potential role of mesenchymal stem cells in a hypoxia model induced by sodium nitrite in testes of male albino rats

et al. 2017

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Introduction: The present work aims to examine the possible role of stem cells on biochemical markers and histopathological alterations of hypoxia caused by sodium nitrite (NaNO 2 ) toxicity in testes of male rats. Methods: In this study, 96 adult male albino rats were divided into 6 groups (16 rats each). Group 1 (G1) was the control group and received distilled H 2 O. Group 2 (G2) received daily NaNO 2 (35 m/kg bwt/ day) via subcutaneous injection for 3 weeks. Group 3 (G3) received NaNO 2 for 2 weeks and were then injected once with 2*10 6 mesenchymal stem cells (MSCs) intravenously and sacrificed 4 weeks later. Group 4 (G4) received NaNO 2 for 2 weeks and were then injected with 2*10 6 MSCs followed by daily NaNO 2 injection for 1 week; rats in G4 were sacrificed 4 weeks from MSCs treatment. Group 5 (G5) rats were treated with NaNO 2 for 2 weeks and then left to recover for 4 weeks. Finally, Group 6 (G6) rats were treated with NaNO 2 for 3 weeks and left to recover for 3 weeks, after which point they were sacrificed. Results: The results showed that NaNO 2 caused oxidative damage and histopathological alterations in the rat testes, as well as increased the levels of testes malondialdehyde (MDA), nitric oxide (NO) and DNA fragmentation percentage (DNA F %). Moreover, NaNO 2 decreased the elevated activities of testes catalase (CAT) and total antioxidant activity (TAA), in comparison to the control group. The histological results illustrated different distortions, vacuolization and lipid accumulations in interlobular space as well as diminution of inter cellular germ cell layers, absence of Leydig cells, irregular basement membrane of tubule, and separation within spermatogenic cells. In

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Section: Discussionsupporting

confidence: 82%

The potential role of mesenchymal stem cells in a hypoxia model induced by sodium nitrite in testes of male albino rats

et al. 2017

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“…Venous stasis-induced hypoxia, iNOS up-regulation, malondialdehyde (MDA), and nitric oxide (NO) generation in the varicocelized testes have been previously reported [Romeo et al 2003;Turkyilmaz et al 2004].…”

Section: Introductionmentioning

confidence: 99%

Silymarin protects from varicocele-induced damages in testis and improves sperm quality: evidence for E2f1 involvement

Moshtaghion¹,

Malekinejad²,

Razi

et al. 2013

Systems Biology in Reproductive Medicine

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This study was designed to evaluate the protective effect of silymarin (SMN) on varicocele-induced damage in testis and its effects on sperm parameters and on antioxidant status. Wistar rats were divided into three groups: control-sham, varicocele-induced, and SMN-treated varicocelized (50mg/kg, orally) rats. The sperm count, DNA integrity, and histone-protamine transition was evaluated after 42 days. The antioxidant status was analyzed by determining testicular malondialdehyde (MDA) and total thiol molecules (TTM). The endocrine status of the testicular tissue was estimated by counting the normal Leydig cell distribution/mm 2 and by determination of serum testosterone. The expression of E2f1 mRNA was analyzed using RT-PCR. Carbohydrate depletion and lipid foci replacement in germinal cells were examined by histochemical analyses. Silymarin rehabilitated the varicocele-induced Leydig cell degeneration and testosterone reduction. In addition, SMN recovered the varicocele-induced reduction of TTM and lowered significantly (P < 0.05) the varicocele-elevated content of MDA. The SMN treatment resulted in a significant (P < 0.05) down-regulation of the VCL-up-regulated E2f1 mRNA. Silymarin-treated animals were protected from varicoceleinduced testicular atrophy and these animals showed a significant (P < 0.05) increase in the percentage of seminiferous tubules with positive tubular differentiation, repopulation, and spermiogenesis indices. Furthermore, SMN improved the varicocele-induced carbohydrate reduction in germinal cells. Our data suggest that in addition to oxidative stress, alteration in the testicular endocrine function plays a crucial role in the pathogenesis of varicocele. Moreover, the protective effects of SMN on varicocele-induced damage may reflect its antioxidant property, which may be mediated via the E2f1 transcription factor.

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“…Reactive oxygen species/reactive nitrogen species (ROS/RNS) seem to be involved in the oxidative damage in these pathologies (Peltola et al 1995, Romeo et al 2003. In experimental models, heat stress of testis and testicular cells has been associated with spermatocyte apoptosis (Yin et al 1997, Ikeda et al 1999, Lue et al 1999, Rockett et al 2001, Somwaru et al 2004) and ROS formation (Ikeda et al 1999, Ishii et al 2005, with a likely activation of the intrinsic pathway of apoptosis ; see Moreno et al (2012) for a review).…”

Section: Introductionmentioning

confidence: 99%

Differential effects of temperature on reactive oxygen/nitrogen species production in rat pachytene spermatocytes and round spermatids

Pino

Osses²,

Oyarzún³

et al. 2013

Reproduction

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Reactive oxygen species (ROS) and reactive nitrogen species (RNS) like superoxide and nitric oxide are produced by testis and spermatogenic cells in response to heat stress. However, the magnitude and mechanisms of this production in spermatogenic cells have not been described. In this work, we evaluated ROS/RNS production, its pharmacology, mitochondrial oxidative metabolism, membrane potential and antioxidant capacity at different temperatures in isolated rat pachytene spermatocytes and round spermatids. Our results showed an increment in ROS/RNS production by pachytene spermatocytes when increasing the temperature to 40 8C. Instead, ROS/RNS production by round spermatids did not change at temperatures higher than 33 8C. ROS/RNS production was sensitive to NADPH oxidase inhibitor diphenylene iodonium or the mitochondrial complex I inhibitor rotenone. No additive effects were observed for these two compounds. Our results suggest an important mitochondrial ROS/RNS production in spermatogenic cells. Oligomycin-insensitive oxygen consumption (uncoupled oxygen consumption) increased with temperature and was significantly larger in round spermatids than pachytene spermatocytes, indicating a likely round spermatid mitochondrial uncoupling at high temperatures. A similar conclusion can be reached by measuring the mitochondrial membrane potential using rhodamine 123 fluorescence in permeabilized cells or JC-1 fluorescence in intact cells. The antioxidant capacity was higher in round spermatids than pachytene spermatocytes at 40 8C. Our results strongly suggest that at high temperatures (40 8C) pachytene spermatocytes are more susceptible to oxidative stress, but round spermatids are more protected because of a temperature-induced mitochondrial uncoupling together with a larger antioxidant capacity.

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Preliminary report on nitric oxide-mediated oxidative damage in adolescent varicocele

Cited by 72 publications

References 34 publications

The potential role of mesenchymal stem cells in a hypoxia model induced by sodium nitrite in testes of male albino rats

The potential role of mesenchymal stem cells in a hypoxia model induced by sodium nitrite in testes of male albino rats

Silymarin protects from varicocele-induced damages in testis and improves sperm quality: evidence for E2f1 involvement

Differential effects of temperature on reactive oxygen/nitrogen species production in rat pachytene spermatocytes and round spermatids

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