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, 6–12]
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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