in maintenance of spermatogenesis and is responsible for the growth, structural
integrity and functional activities of accessory sex organs as well as it help
in the maintenance of spermatogenesis. During spermatogenesis it plays
important role in the development and maturation of sperm, so decrease in the
level of testosterone may decrease the quality of sperm . Many studies have
shown that testosterone withdrawal from the rat testis results in increased
germ cell apoptosis .
In the present
study AAE administration reduced testosterone level and degenerated Leydig
cells in testis. Since Leydig cells produces testosterone in testis, it is
possible that AAE treatment might have modulated Leydig cell function which
disrupted steroid production in treated animals. Further reduced testosterone
level might have disrupted spermatogenesis and induced infertility in treated
The production of
mature sperm with normal structure and function is the benchmark of male
fertility. This is achieved by normal spermatogenesis and spermiogenesis in the
testis, functional maturation during epididymal transit as well as seminal
plasma contributed by normally secreting accessory sex glands. In the present
study, the histology of the accessory sex glands showed very less secretion in
the lumen and there was less population of spermatozoa in the tubules of
epididymis which most likely account for the reduction in fertility in male
rats. These accessory sex glands provide sperm with a nutritious medium for
gamete transfer and secrete antioxidant enzymes such as catalase, glutathione
peroxidase and superoxide dismutase as
well as free radical scavengers such as Vitamins C and E, hypotaurine etc .
A well-balanced amount of ROS plays an
essential role in maintaining sperm structure, genomic and functional
integrity, as well as preserving the antioxidants in secretions of the male
reproductive tract . The increased susceptibility of spermatozoa to
oxidative stress may be associated with a variety of factors. These include,
among others, the lack of cytoplasm in mature spermatozoa, which could be
associated with a lower overall antioxidant capacity, compared to somatic
cells. The ROS cause damage to sperm, mitochondrial and other cytoplasmic
organelle membrane structures through peroxidation of phospholipids, proteins
and nucleotides .
an important role in normal function as an antioxidant. The important functions
include: the maintenance of the sulfhydryl groups in proteins; translocation of
amino acids across cell membranes; the detoxification of foreign compounds; and
the biotransformation of drugs.
ROS produce oxidative
stress by decreasing enzymatic defenses . Superoxide dismutase constitutes
the first line of coordinated enzymatic defense against ROS by dismutating O2•-
into O2 and H2O2. It has been reported that
the addition of SOD to sperm in culture protects them from oxidative attack
. Some investigators have also reported minor reductions in seminal plasma
SOD activity in infertile men [14,15]. Catalase and glutathione peroxidase are
most crucial for detoxifying H2O2, thereby preventing the
generation of hydroxyl radical by the Fenton reaction. CAT and GPx also protect
SOD against inactivation by H2O2. Reciprocally, SOD
protects CAT and GPx against inhibition by superoxide anion. Some of the
studies have shown a relation between deficient seminal catalase activity and
male infertility [14,15,16].
In the present
study, AAE administration decreased the activities of SOD, CAT, GPx, GR, GST
and GSH levels in testis, seminal
vesicle and prostate. The reduction in the activity of CAT observed in the
present study may reflect inability of cells to eliminate H2O2
produced by AAE which may be due to enzyme inactivation caused by excess
production of ROS.
GPx is primarily
responsible for H2O2 removal in testicular mitochondria
that does not contain catalase. GPx plays a crucial role in scavenging peroxyl
radicals and thereby maintains functional integrity of the cell membrane,
spermatogenesis, sperm morphology, and motility . The continued activity of GPx depends on the regeneration of
reduced glutathione by glutathione reductase (GR). Selective inhibition of GR
reduces the availability of reduced glutathione for maintaining GPx activity,
thereby exposing sperm to oxidative stress .
The coordinated activity of GPx, GR and glutathione clearly play a pivotal role
in protecting sperm from oxidative attack. Glutathione-S-transferase
metabolizes xenobiotics by conjugating with GSH. In fact, GST catalysed
conjugation of GSH with exogenous compounds and endogenous metabolites such as
4-hydroxynonenal is regarded as major cellular defense mechanism against
Thus, the balance
of these enzyme systems may be essential to get rid of superoxide anion and
peroxides generated in subcellular compartments of the testis, prostate and
seminal vesicle. The reduced activity of GPx in the organ homogenates observed
in this study may partly be due to lack of the substrate GSH.
most common markers for hepatic toxicity are serum AST and ALT. When the liver
is damaged by any cause, the levels of these proteins are increased rapidly
. Serum creatinine is used clinically to detect and evaluate kidney injury
and chronic kidney disease [21,22].
Therefore the level of creatinine is significant to any kind of renal
toxicity. This study demonstrates that
oral administration of AAE increases the level of serum ALT, AST and creatinine
significantly at higher dose, however there is no significant damage seen in
the histoarchitechture of both liver and kidney.
authors report no declarations of interest.
wish to acknowledge the financial support received from University Grants
Commission (UGC) to undertake the present study.
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