Effects of vigabatrin, carbamazepine or its combination on the pituitarygonadal axis in male Wistar rats (original) (raw)
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Iranian journal of neurology, 2012
Background: Diminished libido and sexual dysfunction are unusually common among male epileptic patients. The most important etiologic factor may be antiepileptic drugs (AEDs)-induced androgen deficiency. We compared reproductive hormone levels among men with epilepsy taking various AEDs and normal controls. Methods: Subjects were 59 male epileptic patients who aged 24 ± 5 years. They had been receiving lamotrigine (LTG) (n = 17), carbamazepine (CBZ) (n = 18), and sodium valproate (VPA) (n = 15) for at least 6 months. We also recruited 23 healthy controls. Testosterone, estradiol, dehydroepiandrosterone sulfate (DHEAS), sex hormonebinding globulin (SHBG), androstenedione (AND), luteinizing hormone (LH), and follicle stimulatin hormone (FSH) levels and gonadal efficiency (testosterone/LH) were compared between the four groups. The patients and the control group were examined and evaluated for male reproduction by urology and endocrinology services.
Pathophysiology, 2017
The effect of chronic administration of gabapentin, carbamazepine or a gabapentincarbamazepine combination on testicular function in male rats was investigated to determine the effect of combining reduced doses of anti-epileptic drugs on the management of seizures, particularly with respect to the testis sequellae of chronic anti-epileptic administration. Male rats were randomized into four groups (n=10). Each group received daily intraperitoneal (i.p.) injections for 28 days as follows: Group I, normal saline 0.1 mL/day; Group II, gabapentin (GBP) 16 mg/kg/day; Group III, carbamazepine (CBZ) 20mg/kg/day; and Group IV, subtherapeutic doses of both GBP (8mg/kg) and CBZ (10mg/kg)/day. Twenty-four hours after the last treatment, five rats from each group were sacrificed and the remaining rats were allowed to recover for another four weeks. Sperm characteristics, serum testosterone, and histological integrity of the testis was assessed 24 hours after treatment and after 28 days of drug withdrawal. GBP, CBZ, and GBP-CBZ combination significantly reduced the absolute weight of the testis, epididymis, and seminal vesicle (p<0.05). Moreover, epididymal sperm count and morphology were significantly decreased (p<0.05) in GBP, CBZ, and GBP-CBZ groups. Reduction in serum levels of testosterone for all of the treated groups was statistically significant (p<0.05). The cytoarchitecture of the testicular tissue in the testis of CBZ and GBP-CBZ groups showed disorganization. The altered testicular function were almost restored in GBP treated rats. CBZ and GBP-CBZ combination have delayed but reversible antifertility in the rats. Hence, chronic administration of GBP, CBZ, and GBP-CBZ combination reversibly reduced testicular function in male rats.
Please cite this article in press as: O.S. Osuntokun, et al., Chronic administration of gabapentin and a gabapentin-carbamazepine combination reversibly suppress testicular function in male Wistar rats (Rattus norvegicus), Pathophysiology (2017), a b s t r a c t The effect of chronic administration of gabapentin, carbamazepine or a gabapentin-carbamazepine combination on testicular function in male rats was investigated to determine the effect of combining reduced doses of anti-epileptic drugs on the management of seizures, particularly with respect to the testis sequellae of chronic anti-epileptic administration. Male rats were randomized into four groups (n = 10). Each group received daily intraperitoneal (i.p.) injections for 28 days as follows: Group I, normal saline 0.1 mL/day; Group II, gabapentin (GBP) 16 mg/kg/day; Group III, carbamazepine (CBZ) 20 mg/kg/day; and Group IV, sub-therapeutic doses of both GBP (8 mg/kg) and CBZ (10 mg/kg)/day. Twenty-four hours after the last treatment, five rats from each group were sacrificed and the remaining rats were allowed to recover for another four weeks. Sperm characteristics, serum testosterone, and histological integrity of the testis was assessed 24 h after treatment and after 28 days of drug withdrawal. GBP, CBZ, and GBP-CBZ combination significantly reduced the absolute weight of the testis, epididymis, and seminal vesicle (p < 0.05). Moreover, epididymal sperm count and morphology were significantly decreased (p < 0.05) in GBP, CBZ, and GBP-CBZ groups. Reduction in serum levels of testosterone for all of the treated groups was statistically significant (p < 0.05). The cytoarchitecture of the testicular tissue in the testis of CBZ and GBP-CBZ groups showed disorganization. The altered testicular function were almost restored in GBP treated rats. CBZ and GBP-CBZ combination have delayed but reversible antifertility in the rats. Hence, chronic administration of GBP, CBZ, and GBP-CBZ combination reversibly reduced testicular function in male rats.
Antiepileptic drugs alter reproductive endocrine hormones in men with epilepsy
European Journal of Neurology, 2005
Disturbances of reproductive endocrine hormones are more often found in men with epilepsy than in the general population. There is an ongoing debate whether this can be attributed to chronic use of antiepileptic drugs or to the epilepsy itself. The aim of the present study was to evaluate the degree of endocrine disturbances in men with epilepsy compared with healthy controls, and to investigate whether there was a drugspecific effect of valproate (VPA) or carbamazepine (CBZ). Men with epilepsy, 20-40 years old, having used either VPA (n ¼ 16) or CBZ (n ¼ 19) as monotherapy for >2 years were included and compared with age-matched controls. Men with epilepsy (VPA + CBZ) had significantly lower FSH values and higher C-peptide values compared with controls. Regarding possible drug-specific effects, the VPA treated patients had significantly higher dehydroepiandrosterone (DHEAS) levels and lower FSH and LH concentrations compared with the controls, whereas there were no differences in testosterone, testosterone/sexhormone-binding globulin (SHBG) ratio or androstenedione levels. Men on VPA also had significantly lower free carnitine/total carnitine, which may have implications for sperm motility, and also higher insulin and C-peptide concentrations. The CBZ treated patients had significantly lower testosterone/SHBG ratio than the controls. Compared with the CBZ treated patients, men on VPA had significantly higher DHEAS concentrations and lower levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) as well as a lower free carnitine/total carnitine ratio. A marked age dependency was found in all three groups regarding several of the endocrine hormones. In conclusion, drug-specific endocrine effects of VPA and CBZ were found in men with epilepsy. Long-term VPA treatment leads to significant changes in DHEAS, FSH, LH, insulin, C-peptide and carnitine ratio. Long-term CBZ treatment leads to significant lower testosterone/SHBG ratio. A strict age matching were found to be of importance in the evaluation of endocrine function in men.
Evaluation of sex hormones and sperm parameters in male epileptic patients
Acta Neurologica Scandinavica, 2018
The aim of this study was to investigate the effect of carbamazepine (CBZ) and sodium valproate (VPA) monotherapy on sexual functions, sex hormones, and semen analysis and quality in male patients with epilepsy. Methods: A total of 59 male patients with epilepsy, of which 30 were on VPA monotherapy and 29 were on CBZ monotherapy, were included in the study between January 2015 and March 2016. A control group was established with 30 healthy males. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), free testosterone (fT), estradiol (E2), sex hormone-binding globulin (SHBG) levels and bioactive testosterone (BAT)/bioactive estradiol (BAE), and BAT/LH ratio were studied in groups. All groups received semen analysis and International Index of Erectile Function Scale (IIEF-5) test for erectile dysfunction. Results: E2 and DHEAS levels were higher in VPA and CBZ groups compared to control group (P < .001, P = .014). The decrease in fT levels in the VPA group was statistically significant (P = .038). No significant difference was detected in levels of SHBG, LH, and FSH (P > .05). BAT/BAE ratios were low both in VPA and CBZ groups (P < .001; P < .001), while BAT/LH ratios were low only in CBZ group (P = .033). In semen analysis, semen volume and number of normal sperms were found to be significantly lower in patients receiving antiepileptic drugs compared to control group (P < .05). There were no differences between the groups in rates of abnormal sperm morphology. IIEF-5 scores were found to be significantly lower in VPA and CBZ groups (P < .001). Conclusion: VPA or CBZ therapy may lead to dysregulation of sex hormones, sexual dysfunction, and alterations in semen analysis in male patients with epilepsy. This must be considered for the selection of antiepileptic drugs in young male patients.
Journal of Reproduction and Development, 2003
The effect of vinclozolin (VCZ), used as a fungicide and known to have anti-androgenic effects on spermatogenesis and gene expression in the male rat testis was investigated. In Experiment 1, VCZ (100 mg/kg/day) or flutamide (FM, 25 mg/kg/day) was orally administered to male Holzman rats for six days. 8 days after the last administration (D8), a drastic increase in intratesticular testosterone was detected in FM (4.2-fold over control) but not in VCZ treated animals, whereas on D36 post-administration, both groups showed similar levels. Significant decreases in daily sperm production were seen in both VCZ and FM-treated rats on D36. Semiquantitative RT-PCR analysis with testicular and pituitary mRNAs on D8 revealed that LHβ and FSHβ mRNAs were increased in the pituitary by VCZ, as well as by FM. Among the four testicular steroidogenic enzyme genes, cytochrome P450 side chain cleavage (P450scc) and cytochrome P450 17α/C17-20 lyase (P450c17) mRNAs were significantly increased, whereas 17β-hydroxysteroid dehydrogenase type III (17βHSD) mRNA was not changed. A significant increase in 3β-hydroxysteroid dehydrogenase type I (3βHSD) and a decrease in androgen receptor (AR) mRNA were observed only in FM treated rats. Immunohistochemistry demonstrated intense staining of P450scc in the interstitial cells of VCZtreated testis on D8. In Experiment 2, hormone levels were measured at 1, 3, 6, 12 and 24 hours after VCZ (100 mg/kg) administration to Sprague-Dawley rats. Serum LH level remained constant for the first 3 hours and started to increase at 6 hrs. In contrast, serum and intratesticular testosterone levels increased 2-fold at 1 hr and maintained the level until 24 hrs. P450c17 mRNA level was 2-fold increased at all periods, whereas no obvious changes were detected in the other steroidogenic enzyme genes. Although not statistically significant, AR mRNA level increased 2-fold, 3 hrs after VCZ administration. These results indicate that VCZ affects the pituitary in a similar manner as FM, but functions differently on testicular gene expression.
Carbamazepine damage to rat spermatogenesis in different sexual developmental phases
International Journal of Andrology, 2009
Carbamazepine (CBZ) is a first-line antiepileptic drug (AED), although it is also utilized for treatment of psychiatric disorders and neuropathic pain. The utilization of CBZ has been associated with damage to male reproduction including hormonal alterations, sexual dysfunction and reduction of sperm quality. Wide and long-term use of CBZ has been a common schedule for children and adolescents, despite the fact it alters the testosterone level in adult rats and humans. In addition, hypothalamic-pituitary-gonadal (HPG) axis during pre-puberty and puberty is more susceptible to toxic agents than in adult phase. The objective of this work was to evaluate the side effects of CBZ on the spermatogenic process of rats from pre-puberty to puberty and sexual maturation. Damage on the seminiferous epithelium, testicular interstitial oedema, reductions of testosterone levels and an increase in oestradiol levels were observed in rats, which were CBZ-treated since the weaning. The results suggest that CBZ, when administered from pre-puberty, provokes specific side effects on rat testes, resulting in more severe damage in the adult phase.
How to Cite this Article: Noorah Saleh AL-Sowayan, Aliyah Tariq Sheikh. Reiterate and integrate the adverse effect of antipsychotic agent and its attenuation by Ginkgo Biloba Extract on reproductive system and functions of rodents World J Pharm Sci 2017; 5(8): 118-135. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which allows adapt, share and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. ABSTRACT The psychotic drug agents are linked and believed to increase risk of sexual dysfunction by increasing prolactin levels. Ginkgo Biloba Extract (GBE) is reported much effected in treating antidepressant induce sexual dysfunction. The current study was carried out in two phases. In first phase of study we did the evaluation of effect of hyperprolactinemia caused by CPZ(Chlorpromazine)on ovarian follicular growth, gonadotrophin and changes in ovarian hormone in adult female rats while in second phase investigation of prophylactic role of GBE against testicular damage, oxidative stress and caudal sperm indices in CPZ treated rodent model was done. In 1 st study we divided the animals in 4 groups, each group was consisting of 5 rats.1 st group was control while other three groups were treated with different doses of CPZ e. g 5mg/kg/day,15mg/kg/day, and 30mg/kg/day respectively for 2 weeks, CPZ was given via gavage. On 15 th day, the animals were sacrificed by decapitated, ovaries were removed and stained with H&E and later their histomorphometric examination was done. The serum levels of LH (Luteinizing hormone), FSH (Follicle Stimulating Hormone), Estradiol (E2), Progesterone and Prolactin levels were measured. CPZ treated groups showed varied amount and size of atretic follicle. The Higher rate of dysfunctional ovaries were seen in those groups which were treated with higher doses of CPZ. Similarly, higher concentration of progesterone and prolactin while lower concentration of FSH, E2, LH in sera and decreased rate of pregnancy was also observed in treated groups. The rate of toxicity was directly proportion to quantity of CPZ dose. In 2 nd phase of study the animals were divide into 5 groups and each had 5 rats.1 st was control,2 nd was treated with CPZ alone while other 3 were firstly treated with single dose of CPZ (30 mg/kg) and then treated with different doses of GBE i-e 45mg/kg,90mg/kg, and 200mg/kg respectively for 20 days. CPZ and GBE were given via gavage. On 21st day, at the end of experiment, the animals were sacrificed by de-capitated using guillotine and then their reproductive organs (testis, epididymis) were removed for further study. Decreased weight of testis and epididymis was also noted in CPZ treated groups. Moreover, degeneration of seminiferous tubules, reduction in sperm motility and count was also observed after CPZ toxicity. In addition to this, increase in the germ cell apoptosis was also noted; the levels of SOD, Testosterones, and CAT got reduced while MDA was increased in treated groups. The groups treated with GBE showed visible and significant improvement in all above said pathological alterations. The results of current study showed that 200mg/kg dose of GBE was more effective in protecting rodents against reproductive toxicity caused by CPZ.
Gonadotoxicity evaluation of oral administration of Zidolam in male albino rats
2010
Zidolam is an antiretroviral combination therapy consisting of zidovudine and lamivudine for the treatment of Human Immunodeficiency Virus (HIV) infection. The objective of this research is to investigate the relationship between oral administration of zidolam and fertility in adult male albino rats Material and Methods. Fifteen male albino rats with body weight (bwt) of 150 -220 gm were used for the 2-phase study. Solution of the drug in sterile water was administered via oral cannula to 5 male rats each at daily dose of 1.29 mg/100 gm bwt respectively for 21 days during phase I. Phase II was a recovery study involving 5 male rats exposed to dose regimen as in phase I, and sacrificed after 21-day withdrawal of treatment. The control group of 5 male rats was given sterile water ad-libitum during the period.