The effects of N-acetylcysteine on spermatogenesis and degree of testicular germ cell apoptosis in an experimental model of varicocele in rats

Duarte, Fernando Barroso; Blaya, Rodrigo; Teloken, Patrick; Becker, Daniel M.; Fernandes, Marilda da Cruz; Rhoden, Ernani Luı́s

doi:10.1007/s11255-009-9687-x

Cited by 11 publications

(7 citation statements)

References 11 publications

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“…NAC, on the other hand, can serve as a precursor for GSH in the GSH biosynthetic pathway (Halliwell and Gutteridge, ), thus increasing germ cell and plasma GSH levels and preventing ROS‐ mediated germ‐cell death (Rao and Shaha, ). Alpha‐lipoic acid and NAC also both have protective functions against experimental‐ or xenobiotic‐mediated germ‐cell death (Prahalathan et al, ; Payabvash et al, ; Farombi et al, ; Duarte et al, ; Reddy et al, ; Nagda and Bhatt, ). In the present study, combined supplementation with both α‐lipoic acid and NAC significantly prevented exercise‐induced testicular dysfunctions in spermatogenesis, steroidogenesis, expression of StAR and androgenic enzyme genes, cellular oxidant and antioxidant status, glutathione redox ratio, ΔΨ m , and intracellular ATP levels (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, NAC is also able to increase GSH content (Afaq et al, ). Furthermore, α‐lipoic acid and NAC both have protective functions against experimental‐ or xenobiotic‐mediated germ‐cell death (Prahalathan et al, ; Payabvash et al, ; Duarte et al, ; Nagda and Bhatt, ; Reddy et al, ). Therefore, the present study was designed to investigate a possible protective function for α‐lipoic acid and NAC on the intensive swimming‐induced germ‐cell death in adult male rats, particularly by altering testicular pro‐ and antioxidant status.…”

Section: Introductionmentioning

confidence: 99%

“…For example, α‐lipoic acid and NAC supplementation reduced tissue GSH oxidation; improved mitochondrial membrane potential (ΔΨ m )—a metric of testicular and sperm physiology (Wang et al, ); and protected the body against exercise‐induced oxidative stress (Sen and Packer, ; Zembron‐Lacny et al, , ). Alpha‐lipoic and NAC are also used to combat oxidative‐stress‐induced testicular damage (Prahalathan et al, ; Duarte et al, ; Nagda and Bhatt, ; Reddy et al, ). Mechanistically, the redox pair lipolic acid/dihydrolipoic acid acts as a powerful reducing agent that can generate GSH from GSSG, ascorbate from dehydroascorbate, or α‐tocopherol from a tocopheryl radical (Halliwell and Gutteridge, ).…”

Section: Introductionmentioning

confidence: 99%

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Alpha‐lipoic acid andN‐acetylcysteine protects intensive swimming exercise‐mediated germ‐cell depletion, pro‐oxidant generation, and alteration of steroidogenesis in rat testis

Jana

Dutta

Chakraborty

et al. 2014

Molecular Reproduction Devel

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Prolonged and strenuous exercise has been proposed as a possible source of male-factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α-lipoic acid and N-acetylcysteine (NAC) on intensive swimming-induced germ-cell depletion in adult male rats. Forced exhaustive swimming of 1 hr/day, 6 days/week for 8 consecutive weeks resulted in a significant (P < 0.05) reduction in epididymal sperm; testicular androgenic enzyme activities; and plasma and intra-testicular testosterone; and produced different types of germ cells in the seminiferous epithelium cycle. Conversely, plasma corticosterone levels and sperm-head abnormalities increased. Western-blot analysis showed a considerable decrease in testicular StAR protein expression whereas reverse-transcriptase PCR analysis showed no significant change in cytochrome P450scc (Cyp11a1) gene expression. Significant (P < 0.05) elevation in testicular reactive oxygen species (ROS), lipid peroxidation, protein carbonyl content versus reduction in glucose-6-phosphate dehydrogenase, glutathione peroxidase, glutathione S-transferase, and caspase-3 activities along with a depletion in the glutathione pool, mitochondrial membrane potential (▵ψm ), and intracellular ATP generation. A considerable level of DNA damage in testicular spermatogenic cells were also noted following forced extensive swimming. Alpha-lipoic acid and NAC supplementation prevented the swimming-induced testicular spermatogenic and steroidogenic disorders by lowering ROS generation. We therefore conclude that intensive forced swimming causes germ-cell depletion through the generation of ROS and depletion of steroidogenesis in the testis, which can be protected by the co-administration of α-lipoic acid and NAC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alpha‐lipoic acid andN‐acetylcysteine protects intensive swimming exercise‐mediated germ‐cell depletion, pro‐oxidant generation, and alteration of steroidogenesis in rat testis

Jana

Dutta

Chakraborty

et al. 2014

Molecular Reproduction Devel

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show abstract

“…The protective effect of NAC on testicular damage and dysfunction were explained in studies of Cay et al, 2006;Payabvash et al, 2007;Farombi et al, 2008;Aktas et al, 2010;Duarte et al, 2010. They showed that NAC had good effects on testicular dysfunction but they did not examine testicular gene alterations that examined in our study.…”

Section: Ajptmentioning

confidence: 69%

Potential Ameliorative Role of N-Acetylcysteine Against Testicular Dysfunction Induced by Titanium Dioxide in Male Albino Rats

El-Kirdasy¹

2014

American Journal of Pharmacology and Toxicology

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In this study, we examined the ameliorative action of N-Acetylcysteine (NAC) against Titanium Dioxide (TiO2) induced testicular degeneration in albino rats. Adult male albino rats were given saline as a control group, TiO2 (1200 mg kg −1 BW), NAC (100 mg kg −1 BW) and co-treatment of NAC and TiO2 as a protective group for 3 months. Testicular tissues were extracted for changes in testicular gene expression and histopathology. Administration of TiO2 significantly up-regulated mRNA expression of IL-6 and TNF-α and normalized by NAC administration. TiO2 administration down regulated Glutathione-S-Transferase (GST) while increased B-cell Lymphoma2 (BcL2) expressions. Co-administration of rats by NAC together with TiO2 normalized changes in GST and BcL2 expression. Expression of steroidogenesis related genes [Androgen Binding Protein (ABR), 17β-Hydroxysteroid Dehydrogenase (17β-HSD), cytochrome P450 17A (CYP17α) and aromatase] showed down regulation in TiO2 administered groups and normalized when NAC given together with TiO2. Moreover, TiO2 induced toxicity in testes that accompanied by degeneration in seminiferous tubules with congestion, oedema and cell disruption that are partially normalized by co-administration of NAC with TiO2. In conclusion, the present findings confirmed the benficial effect of NAC to prevent apoptosis in spermatogenic and sertoli cells and testicular dysfunction induced by TiO2 in male albino rats.

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“…Recently it has been reported from our laboratories that chronic hCG treatment to rats induces Leydig cell apoptosis [14]. N-Acetyl-L-cysteine (NAC) is a well established thiol antioxidant and has been effectively utilized to alleviate oxidative stress following experimentally induced conditions like testicular torsion [15], varicocele [16] and ischemia/reperfusion injury in rat testis [17]. NAC was also shown to prevent testicular germ cell apoptosis induced through H 2 O 2 exposure in vitro [18].…”

Section: Introductionmentioning

confidence: 99%

N-acetyl-l-cysteine modulates multiple signaling pathways to rescue male germ cells from apoptosis induced by chronic hCG administration to rats

et al. 2012

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The present study was aimed to investigate the beneficial effects of N-acetyl-L: -cysteine (NAC, 150 mg/kg bw twice/week) against testicular germ cell apoptosis in rats induced by chronic hCG administration (100 IU/rat/day for 30 days). NAC co-treatment improved serum testosterone, prevented rise in lipid peroxidation, intracellular H(2)O(2) and the activities of antioxidant enzymes in germ cells. Replenishment of intracellular GSH and total antioxidant capacity was seen. There was a marked reduction in TUNEL positive germ cells and expression of caspase-3 (p < 0.01) and PARP cleavage. Pro-apoptotic markers Fas, FasL, caspase-8 were also significantly downregulated. While Bcl-2 was fully restored, rise in Bax, caspase-9, phospho-JNK/JNK and phospho-c-Jun/c-Jun expression was significantly arrested. Anti-apoptotic phospho-Akt/Akt and NF-κB were otherwise found upregulated. Taken together, the above findings demonstrate that NAC intervention rescued the testicular germ cells from demise following chronic hCG treatment through regulation of multiple signaling mechanisms of metazoan apoptosis.

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The effects of N-acetylcysteine on spermatogenesis and degree of testicular germ cell apoptosis in an experimental model of varicocele in rats

Cited by 11 publications

References 11 publications

Alpha‐lipoic acid andN‐acetylcysteine protects intensive swimming exercise‐mediated germ‐cell depletion, pro‐oxidant generation, and alteration of steroidogenesis in rat testis

Alpha‐lipoic acid andN‐acetylcysteine protects intensive swimming exercise‐mediated germ‐cell depletion, pro‐oxidant generation, and alteration of steroidogenesis in rat testis

Potential Ameliorative Role of N-Acetylcysteine Against Testicular Dysfunction Induced by Titanium Dioxide in Male Albino Rats

N-acetyl-l-cysteine modulates multiple signaling pathways to rescue male germ cells from apoptosis induced by chronic hCG administration to rats

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