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Glutathione (GSH) in Male Infertility

Glutathione therapy for male infertility
Lenzi A, Lombardo F, Gandini L, Culasso F, Dondero F. [Arch Androl 1992 Jul-Aug;29(1):65-8]
Eleven infertile men were treated with glutathione (600 mg/day IM) for 2 months. The patients were suffering from dyspermia associated with various andrological pathologies. Standard semen and computer analyses of sperm motility were carried out before treatment and after 30 and 60 days of therapy. Glutathione exerted significant effect on sperm motility patterns. Glutathione appears to have a therapeutic effect on some andrological pathologies causing male infertility.

Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility
Lenzi A, Culasso F, Gandini L, Lombardo F, Dondero F. [Hum Reprod 1993 Oct;8(10):1657-62]
Glutathione therapy was used for 2 months in a placebo-controlled double-blind cross-over trial of 20 infertile patients with dyspermia associated with unilateral varicocele (VAR) or germ-free genital tract inflammation (INF). Glutathione therapy demonstrated a statistically significant positive effect on sperm motility, in particular on the percentage of forward motility, the kinetic parameters of the computerized analysis and on sperm morphology. The findings of this study indicate that glutathione therapy could represent a possible therapeutical tool for both of the selected andrological pathologies.
Publication Types: Clinical Trial
Randomized Controlled Trial

Glutathione treatment of dyspermia: effect on the lipoperoxidation process
Lenzi A, Picardo M, Gandini L, Lombardo F, Terminali O, Passi S, Dondero F. [Hum Reprod 1994 Nov;9(11):2044-50] We recently introduced reduced glutathione into the therapeutic protocols in some selected cases of dyspermia. This therapy improved semen quality both in a pilot follow-up study and in a double-blind cross-over trial. This improvement was seen in patients with varicocele and germ-free genital tract inflammation, two pathologies in which production of reactive oxygen species or other toxic compounds could have a pathogenic role. Polyunsaturated fatty acids of phospholipids play a major role in membrane constitution and function and are one of the main targets of the lipoperoxidative process. Therefore, to understand the therapeutic action of reduced glutathione, we selected infertile patients and studied the modifications produced by the therapy in seminal parameters, biochemical sperm membrane parameters, and the pattern of fatty acids of phospholipids from blood serum and red blood cell membranes (a model widely accepted as representative of general cell membrane status). The results showed an improvement in both sperm parameters and cell membrane characteristics. This study suggests that biochemical modifications in membrane constitution could explain the seminal results of glutathione therapy. On the other hand, it seems likely that only subjects with systemic membrane disturbances associated with andrological pathologies express this membrane damage in spermatozoa, resulting in dyspermia. This sperm alteration can be partially reversed by glutathione therapy if the structural cell membrane damage is not too severe.
Publication Types: Clinical Trial

Controlled Clinical Trial

Glutathione as a Treatment for Male Infertility (PDF)
D. Stewart Irvine [Reviews of Reproduction (1996) 1, 612]

A rationale for glutathione therapy
Lenzi A, Gandini L, Picardo M. [Hum Reprod. 1998 Jun;13(6):1419-22.] Department of Medical Pathophysiology, University of Rome La Sapienza, Italy.

Glutathione in spermatozoa and seminal plasma of infertile men
Ochsendorf FR, Buhl R, Bastlein A, Beschmann H. [Hum Reprod 1998 Feb;13(2):353-9] Zentrum Dermatologie und Venerologie, Frankfurt am Main, Germany.
Glutathione has a central role in the defence against oxidative damage; however, the data on glutathione concentrations in the semen of infertile men are limited. This study demonstrated that intracellular glutathione levels of spermatozoa are decreased in certain populations of infertile men.

Status of vitamin E and reduced glutathione in semen of oligozoospermic and azoospermic patients
A. Bhardwaj, A. Verma, S. Majumdar, K. L. Khanduja [Asian J Androl 2000 Sep; 2: 225-228]
Departments of Biophysics and Experimental Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
Aim: To investigate the status of seminal plasma reduced glutathione (GSH) and vitamin E in three different conditions of spermatogenesis: azoospermia, oligozoospermia and normospermia. Levels of reduced glutathione were also significantly decreased in oligospermic and azoospermic group, and the reduction in azoospermic group (76.73%) was more pronounced than oligozoospermic group (62.07%). Conclusion: The decrease in reduced glutathione, an endogenous antioxidant, levels in azoospermic and oligozoospermic conditions may cause disruption in the membrane integrity of spermatozoa as a consequence of increased oxidative stress.

Relationship between oxidative stress, semen characteristics, and clincial diagnosis in men undergoing infertility investigation
Pasqualotto FF, Sharma RK, Nelson DR, Thomas AJ Jr, Agarwal A.
[Fertil Steril 2000;73:459-64]

Oxidative stress in normospermic men undergoing infertility evaluation
Pasqualotto FF, Sharma RK, Kobayashi H, Nelson DR, Thomas AJ Jr, Agarwal A. [J Androl. 2001 Mar-Apr;22(2):316-22] We conclude that oxidative stress is associated with male factor infertility. The presence of oxidative stress in infertile normospermic men may explain previously unexplained cases of infertility otherwise attributed to female factors.

Lipoperoxidation damage of spermatozoa polyunsaturated fatty acids (PUFA): scavenger mechanisms and possible scavenger therapies
Lenzi A, Gandini L, Picardo M, Tramer F, Sandri G, Panfili E. [Front Biosci 2000 Jan 1;5:E1-E15] The lipid metabolism in sperm cells is important both as one of the main sources for energy production and for cell structure. Testis germ cells as well as epididymal maturing spermatozoa are endowed with enzymatic and non-enzymatic scavenger systems to prevent lipoperoxidative damage. Seminal plasma also has a highly specialized scavenger system that defends the sperm membrane against lipoperoxidation and the degree of PUFA insaturation acts to achieve the same goal. Systemic predisposition and a number of pathologies can lead to an anti-oxidant/pro-oxidant disequilibrium. Scavengers, such as GSH, can be used to treat these cases as they can restore the physiological constitution of PUFA in the cell membrane. The results of GSH therapy are presented and discussed.
Publication Types: Clinical Trial

Polyunsaturated fatty acids of germ cell membranes, glutathione and blutathione-dependent enzyme-PHGPx: from basic to clinic
Lenzi A, Gandini L, Lombardo F, Picardo M, Maresca V, Panfili E, Tramer F, Boitani C, Dondero F. [Contraception 2002 Apr;65(4):301-4] Laboratory of Seminology and Immunology of Human Reproduction, Department of Medical Pathophysiology, University of Rome La Sapienza, Italy.

Biochemistry of the induction and prevention of lipoperoxidative damage in human spermatozoa
Storey BT. [Mol Hum Reprod 1997 Mar;3(3):203-13] Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia 19104-6080, USA.
Lipid peroxidation occurs in human sperm cells with damage to the cell plasma membrane, leading to loss of cytosolic components and hence to cell 'death'. Human spermatozoa possess the anti-lipoperoxidative defence enzymes, superoxide dismutase (SOD) and glutathione peroxidase plus glutathione reductase (GPX/GRD). The essential role of GPX/GRD is inferred from the observation that inhibition of GPX, either with mercaptosuccinate or with complete oxidation of intracellular reduced glutathione, results in a 20-fold increase in peroxidation rate. Human spermatozoa appear to have enough anti-lipoperoxidative defensive capacity for lifetimes long enough for fertilization but still short enough for ready removal from the female reproductive tract in good time. Too low a defence capacity could lead to male infertility.

Oxidative stress and role of antioxidants in normal and abnormal sperm function
Suresh C. Sikka, Ph.D., HCLD [Frontiers in Bioscience 1, e78-86, August 1,1996]
Department of Urology, Tulane University School of Medicine, New Orleans, Louisiana, USA
Spermatozoa, unlike other cells, are unique in structure, function, and susceptibility to damage by LPO. Mammalian spermatozoa are rich in polyunsaturated fatty acids and, thus, are very susceptible to ROS attack which results in a decreased sperm motility, presumably by a rapid loss of intracellular ATP leading to axonemal damage, decreased sperm viability, and increased midpiece morphology defects with deleterious effects on sperm capacitation and acrosome reaction. Lipid peroxidation of sperm membrane is considered to be the key mechanism of this ROS-induced sperm damage leading to infertility.

Studies on the origin of redox enzymes in seminal plasma and their relationship with results of in-vitro fertilization
Yeung CH, Cooper TG, De Geyter M, De Geyter C, Rolf C, Kamischke A, Nieschlag E.
Mol Hum Reprod. 1998 Sep;4(9):835-9.

Seminal plasma reduces exogenous oxidative damage to human sperm, determined by the measurement of DNA strand breaks and lipid peroxidation
Potts RJ, Notarianni LJ, Jefferies TM. Mutat Res. 2000 Feb 14;447(2):249-56.

Relative impact of oxidative stress on male reproductive function
Sikka SC. [Curr Med Chem. 2001 Jun;8(7):851-62.]

Male infertility: nutritional and environmental considerations
Sinclair S. [Altern Med Rev 2000 Feb;5(1):28-38] Studies confirm that male sperm counts are declining, and environmental factors, such as pesticides, exogenous estrogens, and heavy metals may negatively impact spermatogenesis. A number of nutritional therapies have been shown to improve sperm counts and sperm motility, including carnitine, arginine, zinc, selenium, and vitamin B-12. Numerous antioxidants have also proven beneficial in treating male infertility, such as vitamin C, vitamin E, glutathione, and coenzyme Q10. Acupuncture, as well as specific botanical medicines, have been documented in several studies as having a positive effect on sperm parameters. A multi-faceted therapeutic approach to improving male fertility involves identifying harmful environmental and occupational risk factors, while correcting underlying nutritional imbalances to encourage optimal sperm production and function.



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