Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for male factor infertility?

Oeda, Tadashi; Henkel, Ralf; Ohmori, Hitoshi; Schill, Wolf‐Bernhard

doi:10.1111/j.1439-0272.1997.tb00305.x

Cited by 98 publications

(64 citation statements)

References 35 publications

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“…Some studies have shown that antioxidants (e.g., vitamin E, glutathione, N-acetyl cysteine, catalase and ferulic acid) are effective in reducing ROS levels and in preventing the decline in sperm motility during sperm processing. [93][94][95][96] In contrast, other studies have reported that antioxidants (e.g., glutathione and catalase) are ineffective in protecting spermatozoa from the loss of motility during sperm processing. [97][98][99] It is important to note that sperm samples from infertile men may be more susceptible to oxidative injury (from semen processing) and be afforded greater protection by antioxidants than samples from fertile men.…”

Section: Role Of In Vitro Antioxidants In Protecting Spermatozoa Frommentioning

confidence: 74%

Antioxidant therapy in male infertility: fact or fiction?

Zini¹,

Alhathal²

2011

Asian J Androl

111

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Infertile men have higher levels of semen reactive oxygen species (ROS) than do fertile men. High levels of semen ROS can cause sperm dysfunction, sperm DNA damage and reduced male reproductive potential. This observation has led clinicians to treat infertile men with antioxidant supplements. The purpose of this article is to discuss the rationale for antioxidant therapy in infertile men and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm function and DNA damage. To date, most clinical studies suggest that dietary antioxidant supplements are beneficial in terms of improving sperm function and DNA integrity. However, the exact mechanism of action of dietary antioxidants and the optimal dietary supplement have not been established. Moreover, most of the clinical studies are small and few have evaluated pregnancy rates. A beneficial effect of in vitro antioxidant supplements in protecting spermatozoa from exogenous oxidants has been demonstrated in most studies; however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established conclusively. Keywords: antioxidant; male infertility; oxidative stress; sperm DNA fragmentation; vitamins RELATIONSHIP BETWEEN OXIDATIVE STRESS AND SPERM DYSFUNCTION Seminal oxidative stress (OS) results from an imbalance between reactive oxygen species (ROS) production and ROS scavenging by seminal antioxidants. Seminal OS is believed to be one of the main factors in the pathogenesis of sperm dysfunction and sperm DNA damage in male infertility.1-4 Indeed, it is estimated that 25% of infertile men possess high levels of semen ROS, whereas fertile men do not have high levels of semen ROS.1,4-6 Although a controlled production of these ROS is required for sperm physiology (sperm hyperactivation, capacitation and acrosome reaction) and for natural fertilization, [7][8][9] the excessive production of ROS by immature germ cells and leukocytes causes sperm dysfunction (lipid peroxidation, loss of motility and sperm DNA damage). 9,10 Spermatozoa are particularly susceptible to oxidative injury due to the abundance of plasma membrane polyunsaturated fatty acids. [10][11][12] These unsaturated fatty acids provide fluidity that is necessary for membrane fusion events (e.g., the acrosome reaction and sperm-egg interaction) and for sperm motility. However, the unsaturated nature of these molecules predisposes them to free radical attack and ongoing lipid peroxidation throughout the sperm plasma membrane. Once this process has been initiated, accumulation of lipid peroxides occurs on the sperm surface (this results in loss of sperm motility) and oxidative damage to DNA can ensue. 13,14SEMINAL ANTIOXIDANT CAPACITY AND SPERM DYSFUNCTION Seminal plasma and spermatozoa themselves are well endowed with an array of protective antioxidants to protect spermatozoa from OS, especially, at the post-testicular level. 6,15,16 Seminal plasma contains a number of high-molecular weigh...

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Section: Role Of In Vitro Antioxidants In Protecting Spermatozoa Frommentioning

confidence: 74%

Antioxidant therapy in male infertility: fact or fiction?

Zini¹,

Alhathal²

2011

Asian J Androl

111

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“…The most noteworthy studies are those performed by Baker et al, 54 Oeda et al 58 and Lopes et al, 5 which showed positive effects with varying doses in vitro. Baker et al 54 observed reduced ROS production and improved motility with doses ranging from 1 to 10 mmol l 21 , whereas Oeda et al 58 observed preserved motility with doses from 0.1 to 15 mg ml 21 and Lopes et al 5 found reduced DNA damage with 0.1 mmol l 21 of NAC.…”

Section: Antioxidant Studies Effectmentioning

confidence: 96%

The role of antioxidant therapy in the treatment of male infertility: an overview

Lombardo¹,

Sansone²,

Romanelli³

et al. 2011

Asian J Androl

100

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In recent years, many studies have focused on the effect of oxidative stress, reactive oxygen species (ROS) and antioxidants on the male eproductive system. Under physiological conditions, sperm produces small amounts of ROS, which are needed for fertilisation, acrosome reaction and capacitation. However, if an increased production of ROS is not associated with a similar increase in scavenging systems, peroxidative damage of the sperm plasma membrane and loss of DNA integrity typically occur, which leads to cell death and reduced fertility. Furthermore, since there is no linear correlation between sperm quality and pregnancy rates, an improvement in semen parameters should not be the sole outcome considered in studies of antioxidant therapies. A definitive conclusion regarding the benefit of these therapies is difficult to obtain, as most of the previous studies lacked control groups, considered different antioxidants in different combinations and doses, or did not evaluate pregnancy rates in previously infertile couples. Even if beneficial effects were reported in a few cases of male infertility, more multicentre, double-blind studies performed with the same criteria are necessary for an increased understanding of the effects of various antioxidants on fertility.

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“…To assess whether PB-and metyrapone-stimulated ROS increase plays an important role in CYP induction, we decided to modulate the cellular ROS production by either overexpression of uncoupling protein 1 (UCP-1) (27) or ROS scavenging by N-acetyl L-cysteine (NAC) (28). Transfection of UCP-1 in LMH cells provoked a considerable decrease of the effect of PB and metyrapone on mRNA levels of both CYP2H1 and CYP3A37 (Fig.…”

Section: Pb and Metyrapone Affect Mitochondrial Membrane Potential Rosmentioning

confidence: 99%

In the regulation of cytochrome P450 genes, phenobarbital targets LKB1 for necessary activation of AMP-activated protein kinase

Blättler

Rencurel

Kaufmann

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Transcriptional activation of cytochrome P450 (CYP) genes and various drug metabolizing enzymes by the prototypical inducer phenobarbital (PB) and many other drugs and chemicals is an adaptive response of the organism to exposure to xenobiotics. The response to PB is mediated by the nuclear receptor constitutive androstane receptor (CAR), whereas the chicken xenobiotic receptor (CXR) has been characterized as the PB mediator in chicken hepatocytes. Our previous results suggested an involvement of AMP-activated protein kinase (AMPK) in the molecular mechanism of PB induction. Here, we show that the mechanism of AMPK activation is related to an effect of PB-type inducers on mitochondrial function with consequent formation of reactive oxygen species (ROS) and phosphorylation of AMPK by the upstream kinase LKB1. Gain-and loss-of-function experiments demonstrate that LKB1-activated AMPK is necessary in the mechanism of drug induction and that this is an evolutionary conserved pathway for detoxification of exogenous and endogenous chemicals. The activation of LKB1 adds a proximal target to the so far elusive sequence of events by which PB and other drugs induce the transcription of multiple genes.drug metabolism ͉ induction ͉ mitochondria ͉ reactive oxygen species E volution has provided organisms with an elaborate defense system against foreign compounds (xenobiotics). The liver of vertebrates contains numerous enzymes that can transform potentially toxic xenobiotics (e.g., nutrients or drugs) or endobiotics (e.g., bile acids) to inactive and excretable metabolites. The expression of these enzymes can be adapted to the needs for detoxification by a process called induction. Phenobarbital (PB) is the prototype of a number of drugs that induce their own and the metabolism of other xenobiotics. Induction of drug metabolism is part of a pleiotropic response of the liver to xenobiotic exposure, which includes liver hypertrophy, tumor promotion, and induction of numerous genes in addition to those encoding for drug-metabolizing enzymes and drug transporters (1). PB also was shown to decrease the transcription of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase 1 (PEPCK1) and glucose-6-phosphatase (G6P), and of several hepatic genes responsible for fatty acid metabolism (2). Moreover, PB increases the transcription of ␦-aminolevulinic acid synthase 1 (ALAS1), the rate-limiting enzyme in the synthesis of heme, the prosthetic group of cytochromes P450 (CYPs) (3, 4). The molecular details of the mechanisms by which PB causes these effects are incompletely understood.The transcriptional activation by PB of genes encoding drugmetabolizing enzymes, such as Cyp2b10 in mouse and CYP2B6 in human, is mediated by the nuclear receptor constitutive androstane receptor (CAR) (5). The interaction of PB with CAR is complex. PB apparently does not bind directly to CAR, but rather triggers its translocation from cytoplasm to the nucleus by as yet unknown mechanisms. In addition, phosphorylation and dephosphorylation events str...

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Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for male factor infertility?

Cited by 98 publications

References 35 publications

Antioxidant therapy in male infertility: fact or fiction?

Antioxidant therapy in male infertility: fact or fiction?

The role of antioxidant therapy in the treatment of male infertility: an overview

In the regulation of cytochrome P450 genes, phenobarbital targets LKB1 for necessary activation of AMP-activated protein kinase

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