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Learn More. Ketamine, an injectable anesthetic in human and animal medicine, is also a recreational drug used by young adults. The aim of this study is to evaluate the effects of ketamine on membrane integrity, DNA fragmentation and sperm parameters in humans. This prospective study was conducted on 40 males with normal semen samples over one month August Sperm analysis was performed for routine parameters, motility and morphology.
Evaluation of membrane integrity and DNA fragmentation was done by eosin-Y staining and the sperm chromatin dispersion SCD test, respectively. Total sperm motility in all case groups were ificantly lower compared with the control group. After addition of ketamine, sperm had evidence of coiled tails in all case groups compared to the control group however this observation was not ificant.
Evaluation of membrane integrity showed the rate of necrospermia increased in all case groups. However, ketamine only ificantly affected membrane integrity in case group III. SCD staining showed that in the control group nucleoids with medium halos Between case groups, nucleoids with large and medium halos showed ificant differences in case groups II and III compared with case group I. Ketamine, through its effect on membrane integrity and DNA fragmentation, decreased sperm viability and caused abnormal sperm parameters in progressive motility.
Ketamine, a non-competitive antagonist at the glutamatergic N-methyl-D-aspartate NMDA receptor is currently used in human and animal medicine as an injectable anesthetic. Ketamine is also a controlled substance, illegally used as a recreational drug 1. In the last five years the percentage of ketamine users has rapidly grown. The reason for prevalent use of ketamine is that people believe it will not lead to physical dependence 2.
Ketamine is absorbable via intravenous, intramuscular, oral, Can ketamine make you infertile topical routes due to both its water and lipid solubility.
It is very short-acting, with hallucinatory effects that last 60 minutes when insufflated or injected and up to two hours when ingested orally, the total experience lasting no more than a couple of hours 3. At sufficiently high doses, users may experience what is called the "K-hole", a state of dissociation whose effects are thought to mimic the phenomenology of schizophrenia 5.
It has been shown that recreational ketamine ingestion has been associated with measurable concentrations of the drug in the blood, urine, brain tissue, spleen, liver and kidneys, and it is excreted in urine and bile 6. Acute dysfunction of visual convergence, poor body coordination and balance, and an increased pulse rate have been observed immediately after ketamine use 7. Some of the effects of ketamine on the nervous system have been identified.
Earlier studies have reported ketamine use to have a ificant detrimental effect on memory function 8. As an acute effect, ketamine mainly activates the prefrontal cortex and the limbic structures 9. It can inhibit reuptake of serotonin, dopamine and norepinephrine, however the mechanism underlying this action is not entirely clear Besides the toxicity to the nervous system, ketamine can affect the lower urinary tract, causing nocturia, dysuria, increased urinary frequency and sometimes hematuria 11 Based on ketamine effects on the urinary system, we hypothesize that the genital system may also be affected; therefore we have investigated the effects of different doses of ketamine on quality of normal human ejaculated sperm DNA and membrane integrity.
Recently, failure of the conventional semen parameters to predict fertilization show that hidden anomalies lie at the sperm membrane level or at the chromatin level.
Plasma membrane function activity is one of the most important aspects of sperm biology that involves metabolic exchanges with the surrounding medium which play an important role in several events during fertilization, capacitation, acrosomal reaction and sperm-oocyte fusion Investigation of membrane integrity seems to offer more information about sperm fertility potential than sperm parameters and probably there is relationship between sperm membrane integrity and sperm parameters 14 We have used a rapid, simple test for this evaluation, the eosin-Y staining test 16 In addition, the integrity of sperm DNA is being recognized as a new parameter of semen quality and a potential fertility predictor.
In the present study we have analyzed DNA integrity of sperm by the sperm chromatin dispersion SCD test based on the principle that sperm with fragmented DNA fail to produce the characteristic halo of dispersed DNA loop observed in sperm with non-fragmented DNA following acid denaturation and removal of nuclear proteins In this prospective study, 40 males were enrolled at Shiraz-Human Assisted Reproductive Center during one month August The semen samples were collected by masturbation after days of sexual abstinence.
After obtaining the normal spermogram, normal samples were selected according to World Health Organization guidelines for the next survey. These doses were selected after ketamine was added to the medium and the viability rate of sperm was observed. Aliquots of 0.
Ketamine: what parents need to know
The slides were immediately immersed horizontally in a tray with freshly prepared acid denaturation solution 0. A glass slide precoated with 0. The denaturation was then stopped and proteins were removed by transferring the slides to a tray with neutralizing and lysing solution 0. Removal of nuclear proteins in nucleoids with a central core and a peripheral halo of dispersed DNA loop. Cells were finally stained with Wright and PBS for 10 minutes. After they were air dried, the degree of DNA dispersion was assessed by bright field microscopy. A minimum of spermatozoa were evaluated by two different observers This staining was performed by mixing 10 ml of sperm sample with 10 ml of dye 0.
A total of sperm cells were counted within a few minutes after the addition of the dye 16 - The mean and standard deviation SD was also calculated for each value. There were control and three case groups of 10 patients per group.
The of sperm parameters at different doses of ketamine are reported in table 1. The mean percentage of sperm morphology decreased slightly in all case groups compared with the control group, but it was not ificant. We evaluated membrane integrity using Eosin-Y staining and observed an increased rate of necrospermia in the case groups compared to the control group. Table 2 showed a substantial difference in the percentage of positive SCD stained spermatozoa. In the control group nucleoids with medium halo Between case groups, nucleoids with large and medium halos showed ificant differences in case group II and III compared with case group I.
Nucleoides from human sperm cells obtained with the sperm chromatin dispersion SCD test.
Nucleoides with large halos of DNA dispersion A. Ketamine is a dissociative anesthetic developed in to replace PCP and presently used in human anesthesia and veterinary medicine. Although it is manufactured as an injectable liquid, in illicit use ketamine is generally evaporated to form a powder and is either snorted or swallowed.
Ketamine is odorless and tasteless, so it can be mixed with beverages without being noticed and it induces amnesia. Because of these properties, the drug is sometimes given to unsuspecting victims and used in the commission of sexual assaults referred to as "drug rape" 21 Ketamine goes by various names on the street.
Ketamine is abused in both the liquid and solid form. The liquid form is usually injected intravenously and is the most dangerous way to consume. The solid form is smoked, snorted or swallowed as a pill and it is known to be added to drinks 23 In the s ketamine abuse, as a new type of drug abuse, appeared in areas of Southeastern China and in high-populated cities and spread quickly into mainland China Most new type drug users are reported to be young, unemployed individuals in their fertility years under 35 years of age.
It is likely that new type drugs will become the most extensive toxic abuse drugs in use in the 21st century instead of the traditional illegal psychoactive drug substances such as heroin and cocaine Until now researchers have mainly studied the neurological and urinary tract effects of ketamine.
For the first time, Tan et al. They found decreased sperm motility after ketamine treatment and suggested that long term ketamine treatment might affect the sperm environment leading to a decline in sperm motility that can affect fertility. In this manner our investigation about the effects of ketamine on quality of normal ejaculated sperms, DNA fragmentation and membrane integrity is not done. For the purposes of this research, we have added ketamine drug to semen samples.
It has been suggested that sperm concentration, motility and normality are three important parameters to evaluate infertility We have found noticeable impact on parameters of human sperm following ketamine adjustment, which included decreased total motility, progressive motility and increased non-progressive motility, but it probably produced slight changes in sperm morphology coiled tail.
Though the mechanism of ketamine effects on sperm parameters is unknown, numerous clinical models support the relationship between semen parameters and increase in reactive oxygen species ROS. Oxidative stress OS represents an imbalance between the productions of ROS or free radicals and the available antioxidant system Pasqualotto et al. Researchers have shown that antioxidant levels in the blood correlated with sperm counts and motility 30 On the other hand, ROS has been shown to correlate with reduced male fertility by causing peroxidative damage to the sperm plasma membrane OS le to lipid peroxidation of sperm membranes rich in unsaturated fatty acids and it has been shown that sperm motility is very closely correlated with sperm membrane integrity 33 The inverse correlation between lipid peroxidation and sperm motility has also been shown by Giwercman et al.
Our findings agreed with the above mentioned research and showed a dose-dependent effect of ketamine on membrane integrity. The Can ketamine make you infertile studies on membrane integrity subsidiary shows decrease of it by ketamine may result into ROS function. It has been shown that OS is a major case of infertility and is intimately related to DNA fragmentation 35 Both testicular and extratesticular factors contribute to the final load of sperm DNA damage in ejaculated sperm. Superoxide and hydrogen radicals are mutagenic species and can cause chromosomal damage In addition, a relationship between sperm motility and DNA damage was shown as a result of the adverse effects of OS Our findings of the chromatin dispersion pattern according to the SCD test after ketamine dosing have shown that abnormalities in sperm parameters reflected DNA structure.
Our demonstrate that ketamine administration ificantly decreases sperm motility, viability and normal chromatin dispersion.
These may disturb male reproductive function. There is no conflict of interest in this article. National Center for Biotechnology InformationU. Int J Fertil Steril. Forouzan AbsalanPh. Sc, 2 and Abdollah ZabihiB. Author information Article notes Copyright and information Disclaimer. Received Mar 11; Accepted Jul