effects of chlorpromazine on reproductive system and function in female rats

Chlorpromazine [CPZ], an antipsychotic drug, is associated with increased risk of sexual dysfunction through increasing prolactin levels. The current study evaluates the effect of CPZ-induced hyperprolactinemia on ovarian follicular growth, gonado-tropins, and alteration of ovarian source hormones. In this experimental study, animals were divided into four groups, control and CPZ [n=8 per group]. In the treated groups, CPZ was administered by gavage at doses of 3, 10 and 30 mg/kg per day for 28 days. On day 29 the animals were killed after which histopathological and histomorphometric analyses of the ovaries were performed. We evaluated the levels of prolactin serum, luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E[2] and progesterone. The ovaries of the test groups showed numerous atretic follicles of various sizes. CPZ caused a significant difference between the test groups and the control group [P<0.05] on the amount of atresia and the size of the normal corpora lutea [CL]. The increased dysfunction of the ovaries from the different groups depended on the amount of CPZ administered. The serum concentrations of prolactin and progesterone significantly increased [P=0.05], while the serum concentrations of estradiol, LH and FSH notably decreased [P=0.05], depending on the CPZ dose. CPZ-induced animals had unsuccessful mating and decreased pregnancy rate. The present findings suggest that CPZ-induced disturbances not only depend on prolactin level but the increased prolactin level is largely dose-dependent

Chlorpromazine-induced hyperprolactinemia on rat's uterus

Hyperprolactinemia is a common side effect of antipsychotic drugs that requires further investigation. The current study was designed to evaluate dose-dependent effect of chlorpromazine [CPZ] on hormonal changes and uterine horn histological structure in rats. Moreover, the mammary glands were analyzed to show hyperprolactinemia-induced histological changes. Albino Wistar rats [n = 32] were divided into four groups. The first group was set as a control. In the three drug-treated groups [eight rats in each group], CPZ was administered by a gavage at doses of 3, 10, and 30 mg/kg/day for 28 days. One day after the last administration of the drug, the animals were sacrificed. Histopathological and histomorphometrical analyses of the uterine horns and mammary glands were carried out to evaluate dose-dependent effect of CPZ on histological structure. Serum levels of prolactin [PRL], estradiol, progesterone, follicle-stimulating hormone [FSH], and luteinizing hormone [LH] were also evaluated. Remarkable [P < 0.05] elevation was observed in CPZ-administrated animals' uterine horn endometrium, myometrium, and perimetrium thicknesses, and the mammary glands were observed with galactorrhea features. The serum level of progesterone and PRL significantly [P < 0.05] increased, while the serum concentration of LH, FSH, and estradiol was notably [P < 0.05] decreased depending on administrated CPZ dose. No histological and biological changes were occurred in the control animals. The present findings suggest that CPZ-induced disturbances not only depend on PRL level and increased PRL level largely depends on administrated doses of the CPZ

Toxic effect of acyclovir on testicular tissue in rats

Background: acyclovir [ACV], a synthetic purine nucleoside analogue, is known to be toxic to gonads

Objective: the current study evaluated cytotoxicity of ACV on histopathological changes in testis tissue and serum testosterone and lipid peroxidation concentrations of male rats

Materials and Methods: animals were divided into five groups. One group served as control and one group served as control sham. In the drug treated groups ACV administered for 15 days. 18 days after the last injection, animals were sacrificed. Histopathological and histomorphometrical analysis of the testis was carried out. Serum levels of testosterone and Lipid Peroxidation and potential fertility of animals was evaluated

Results: male rats exposed to ACV had significant reduction in serum testosterone concentrations at 16 and 48mg/kg dose-levels [p<0.01]. ACV induced histopathological changes in the testis and also increase the mean number of mast cells in peritubular or interstitial tissue in the testis at16 and 48mg/kg dose-levels [p<0.01]. In addition ACV caused increase of serum level of Lipid Peroxidation at 48mg/kg dose-level [p<0.05]. As well ACV decreased potential fertility in male rats

Conclusion: the present results highly support the idea that ACV has adverse effect on the reproductive system in male rat

Effect of purine nucleoside analogue-acyclovir on the sperm parameters and testosterone production in rats

Acyclovir [ACV], a synthetic purine nucleoside analogue derived from guanosine, is known to be toxic to gonads and the aim of this study was to evaluate the effect of ACV on the sperm parameters and testosterone production in rat. In this experimental study, forty adult male Wistar rats [220 +/- 20 g] were randomly divided into five groups [n=8 for each group]. One group served as control and one group served as sham control [distilled water was intraperitoneally [i.p.] injected]. ACV was administered intraperitoneally in the drug treatment groups [4, 16 and 48 mg/kg/day] for 15 days. Eighteen days after the last injection, rats were sacrificed by CO2 inhalation. After that, cauda epididymides were removed surgically. At the end, sperm concentrations in the cauda epididymis, sperm motility, morphology, viability, chromatin quality and DNA integrity were analyzed. Serum testosterone concentrations were determined. The results showed that ACV did not affect sperm count, but decreased sperm motility and sperm viability at 16 and 48 mg/kg dose-levels. Sperm abnormalities increased at 48 mg/kg dose-level of ACV. Further, ACV significantly increases DNA damage at 16 and 48 mg/kg dose-levels and chromatin abnormality at all doses. Besides, a significant decrease in serum testosterone concentrations was observed at 16 and 48 mg/ kg doses. The present results highly support the idea that ACV induces testicular toxicity by adverse effects on the sperm parameters and serum level of testosterone in male rats

[ ultrastructural study of oocyte and zona pellucida in ovarian follicles of untreated and and metformin-treated diabetic rats subsequent to induction of experimental diabetes]

Diabetes is a metabolic disorder affecting the whole body systems including the female reproductive organs. Moreover, diabetes is an important cause of infertility. Metformin is commonly used to control hyperglycemia in patients with diabetes. This study was done to evaluate the ultrastructural changes of ovarian follicles in diabetic rats and their response to metformin. Thirty-six adult Sprague-Dawley female rats [170-210 g] were studied in three groups [Control, diabetic and metformin-treated rats]. In the second and third groups, diabetes was induced by injection of streptozotocin [45 mg/kg]. The rats in the third group were later treated by metformin monohydrochloride [100 mg/kg]. At the end of the experiment, rats were sacrificed and their right ovaries were observed under transmission electron microscope. Quantitative data were analyzed by student t-test in SAS software. In comparison with the control group, significant decreases in zona pellucida thickness and the mean number of microvilli were observed [respectively, P<0.01 and P<0.001] in diabetic rats. Significant decreases in zona pellucida thickness were also observed in metformin-treated rats [P<0.05] but changes in the number of microvilli were non-significant. The number of organelles in oocyte cytoplasm was higher and they were natural or natural-looking in metformin-treated rats versus the diabetic ones. Reduction in the number of mitochondria and their ballooning cristae were of the most noticeable changes in diabetic rats. Diabetes decreases the number of microvilli and oocyte organelles and diminishes zona pellucida thickness leading to structural changes in the organelles but metformin could improve the aforesaid conditions

[Effects of tempol on in vitro development of mouse embryos under oxidative stress]

Etiologically, oxidative stress can be considered as one of the reasons for defective embryonic development which leads to developmental arrest due to necrosis or apoptosis. Under in vivo conditions, multiple mechanisms act to protect the embryo against reactive oxygen species [ROS], but under in vitro conditions most of these mechanisms are absent leading to higher levels of ROS in the culture medium. The objective of this study was to compare the antioxidant effects of Tempol, 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine-l-oxyl, a permeable synthetic antioxidant, on mouse preimplantation embryonic development in vitro conditions in the presence or absence of oxidative stress. Mature oocytes from mouse were retrieved following ovarian stimulation by the administration of Pregnant Mare Serum Gonadotropin [PMSG] and hCG. Upon in vitro fertilization, the zygotes were cultured in different groups in HTF medium containing 4 mg/ml BSA. To study the effects of oxidative stress on embryo development, the zygotes were cultured for an hour in a medium containing different concentrations of H[2]O[2]. After washing, the zygotes were transferred to the culture plate. The zygotes were later placed in the media containing different concentrations of Tempol following their culture in 10 microM H[2]O[2] for one hour to study the effects of different concentrations of the substance in the absence of other oxidative stresses. The data were later compared and statistically analyzed. The pre-implantation embryonic development decreased significantly in the case group, compared to the control group after a short exposure to H[2]O[2], - the effect being more noticeable in higher concentrations. Tempol reduced the impairments resulting from the oxidative stress to some extent. Under in vitro conditions and a concentration of 0.5 microM, Tempol improved embryonic development quality, quantitatively and morphologically. Tempol increased the percentage of two-cell embryos from 91.78% in the control group to 96.99% [p < 0.05], blastocysts from 67.80% in the controls to 81.33% [p < 0.05] in the cases, and significantly decreased embryonic arrest from 32.19% in the controls to 18.67% in the cases [p < 0.05]. ROS has a major role in embryonic arrest, witnessed in embryo cultures in vitro conditions. The present study showed that supplementation of embryo cultures with Tempol improved the embryonic development. It seems that addition of permeable synthetic antioxidants, such as Tempol, to embryo cultures could protect embryos from oxidative damage and improve embryonic development