Effect of acute lithium administration on penile erection: involvement of nitric oxide system

Background: Lithium has been the treatment of choice for bipolar disorder [BD] for many years. Although erectile dysfunction is a known adverse effect of this drug, the mechanism of action by which lithium affects erectile function is still unknown

Objective:The aim was to investigate the possible involvement of nitric oxide [NO] in modulatory effect of lithium on penile erection [PE]. We further evaluated the possible role of Sildenafil in treatment of lithium-induced erectile dysfunction

Materials and Methods:Erectile function was determined using rat model of apomorphine-induced erections. For evaluating the effect of lithium on penile erection, rats received intraperitoneal injection of graded doses of lithium chloride 30 mins before subcutaneous injection of apomorphine. To determine the possible role of NO pathway, sub-effective dose of N [G]-nitro-L-arginine methyl ester [L-NAME], a nitric oxide synthase [NOS] inhibitor, was administered 15 min before administration of sub-effective dose of lithium chloride. In other separate experimental groups, sub- effective dose of the nitric oxide precursor, L-arginine, or Sildenafil was injected into the animals 15 min before administration of a potent dose of lithium. 30 min after administration of lithium chloride, animals were assessed in apomorphine test. Serum lithium levels were measured 30 min after administration of effective dose of lithium

Results: Lithium at 50 and 100 mg/kg significantly decreased number of PE [p<0.001], whereas at lower doses [5, 10 and 30 mg/kg] had no effect on apomorphine induced PE. The serum Li+ level of rats receiving 50 mg/kg lithium was 1 +/- 0.15 mmol/L which is in therapeutic range of lithium. The inhibitory effect of Lithium was blocked by administration of sub-effective dose of nitric oxide precursor L-arginine [100 mg/kg] [p<0.001] and sildenafil [3.5 mg/kg] [p<0.001] whereas pretreatment with a low and sub-effective dose of L-NAME [10mg/kg] potentiated sub-effective dose of lithium, [p<0.001]

Conclusion:These results suggest acute treatments with lithium cause erectile dysfunction in an in-vivo rat model. Furthermore it seems that the NO pathway might play role in erectile dysfunction associated with lithium treatment. Findings also suggest that Sildenafil may be effective in treatment of lithium-associated erectile dysfunction

role of flaxseed and vitamin E on oxidative stress in prepubertal rats with experimental varicocele: an experimental study

Prepubertal varicocele has the most devastating effects on the testes. Oxidative stress is the major cause leading to infertility in varicocele. The antioxidant properties of Flaxseed [FS] treatment in some oxidative diseases have been reported. This study aimed to evaluate the antioxidant effect of FS in prepubertal rats with experimental varicocele. Forty two male prepubertal rats were divided into 6 groups: the varicocele group were either fed with 10% FS, or with regular diet, or with Vit E, the group with sham operation fed with 10% FS, or had regular diet, and control rats who had not been operated but received regular diet. Varicocele was created by Koksal method. After 6 weeks sperm superoxide anion and H[2]O[2] were evaluated by flowcytometery. Semen total antioxidant capacity [TAC] by Koracevic method and testes malondialdehyde [MDA] by thiobarbituric acid with spectrophotometry was measured. While superoxide anion and H[2]O[2] were significantly higher in varicocele grop with regular diet [p=0.0001], FS significantly decreased the previously-mentioned parameters [p=0.0001]. There were no significant differences for seminal TAC between 6 groups [p=0.07]. Left testicular MDA concentration were lower in varicocele or group that were fed with 10% FS compared with other groups [p=0.001]. Reactive oxygen species [ROS] may cause sperm oxidative damage. FS as a fat soluble antioxidant can scavenge intracellular ROS production in varicocele

[Effects of dietary gamma-linolenic acid and docosahexaenoic acid with paclitaxel on the treatment of mice mammary carcinoma]

Breast cancer is one of the most important causes of death in women. One of the various gene expression involved in breast cancer is human epidermal growth factor receptor 2 [HER2/neu] gene expression increases. Factors of dietary affect on regulation of hormone secretion and the rate of breast cancer. One of these factors is amount and type of fats in diet. Gamma-linolenic acid [GLA] and Docosahexaenoic acid [DHA] are members of poly unsaturated fatty acids. In this study, effects of dietary GLA and DHA alone or together with paclitaxel on treatment of mice mammary carcinoma has been evaluated. Thirty female balb/c mice were divided in six groups randomly. Carcinomatous mass induced by tumor implantation method. Spontaneous breast adenocarcinoma of mice were used as tumor stock. The tumors of these mice were removed aseptically, dissected into 0.5 cm3 pieces. These pieces were transplanted subcutaneously into their right flank. GLA and DHA added to the mice diet two week prior to tumor implantation. At the end of intervention, tumors were removed and HER2 gene expression was measured. The weight of animal and tumor volume measured weekly. It was not significant change in the weight of animals that consumed DHA and DHA with taxol. Tumor volume in those groups that received corn oil with taxol [P<0.01], DHA [P<0.05] and DHA with taxol [P<0.001] showed significant decrease in comparison with control group. HER2 gene expression in DHA with taxol decreased significantly in comparison with control group [P<0.05]. Consumption of DHA oil with taxol causes decrease the volume of carcinoma mass. The future studies with large number of sample is needed to support this finding.

A role for endocannabinoids in acute stress-induced suppression of the hypothalamic-pituitary-gonadal axis in male rats / 대한생식의학회지

OBJECTIVE: Stress is known to be an inhibitor of the reproductive hypothalamic-pituitary-gonadal (HPG) axis. However, the neural and molecular connections between stress and reproduction are not yet understood. It is well established that in both humans and rodents, kisspeptin (encoded by the kiss1 gene) is a strong stimulator of the HPG axis. In the present study we hypothesized that endocannabinoids, an important neuromodulatory system in the brain, can act on the HPG axis at the level of kiss1 expression to inhibit reproductive function under stress. METHODS: Adult male Wistar rats were unilaterally implanted with an intracerebroventricular cannula. Afterwards, the animals were exposed to immobilization stress, with or without the presence of the cannabinoid CB1 receptor antagonist AM251 (1 microg/rat). Blood samples were collected through a retro-orbital plexus puncture before and after stress. Five hours after the stress, brain tissue was collected for reverse transcriptase-quantitative polymerase chain reaction measurements of kiss1 mRNA. RESULTS: Immobilization stress (1 hour) resulted in a decrease in the serum luteinizing hormone concentration. Additionally, kiss1 gene expression was decreased in key hypothalamic nuclei that regulate gonadotrophin secretion, the medial preoptic area (mPOA), and to some extent the arcuate nucleus (ARC). A single central administration of AM251 was effective in blocking these inhibitory responses. CONCLUSION: These findings suggest that endocannabinoids mediate, at least in part, immobilization stress-induced inhibition of the reproductive system. Our data suggest that the connection between immobilization stress and the HPG axis is kiss1 expression in the mPOA rather than the ARC.

[ effect of bilateral vasectomy on the serum levels of prooxidant-antioxidant balance [PAB] and lipid peroxidation in rat]

Vasectomy is a widespread contraceptive method in men. In recent years, the number of men who perform vasectomy reversal is increasing. Vasectomy has complications, probably leading to vasectomy reversal failure. It is assumed that oxidative stress is the main cause of these complications. The aim of this study was to investigate the indices of oxidative stress serum after vasectomy. In this experimental study, 42 male rats were divided in 6 groups of seven each: bilateral vasectomy [15, 45 and 90 days] and sham [15, 45 and 90 days] groups. Serum PAB [Prooxidant-Antioxidant Balance] and MDA [Malondialdehyde] as a product of lipid peroxidation were measured 15, 45 and 90 days after intervention. Comparisons between groups were made by Repeated Measure test. Our result showed that serum MDA increase after 15 days was not significant [2.95 +/- 0.12] in comparison to related sham group, but after 45 [3.6 +/- 0.12] and 90 [3.9 +/- 0.31] days the increase, compared to related sham groups 45 [2.28 +/- 0.28] and 90 [2.29 +/- 0.25]days, and also 15 days vasectomy group [2.95 +/- 0.12] were significant [p< 0.001], and there was no significant increase in serum PAB at any times [p > 0.05]. Bilateral vasectomy increased serum levels of MDA. It is supposed that increase in MDA causes adverse effects and unsuccessful reversal vasectomy. By prescribing antioxidants, these effects can be decreased

Acute administration of Zn, Mg, and thiamine improves postpartum depression conditions in mice

Background: Postpartum depression [PPD] affects approximately half of new mothers. Chronic exposure to progesterone during pregnancy and its withdrawal following delivery increases depression and anxiety. In addition, there are complex interactions between hormones, neurotransmitters, and trace elements. Zinc [Zn] and magnesium [Mg] in Auence the nervous system by impacting synaptic neurotransmis-sion in the brain. Thiamine [Vit B[1]] deficiency results in a high percentage of depressive behaviors. Elevated levels of reactive oxygen species in pregnancy are implicated in the pathogenesis of major depression

Methods: We examined the effects of different combinations of Zn, Mg, and Vit B[1] in an animal model of PPD. ZnCl, MgCl, and thiamine-HCl were administered to PPD-induced mice. Depression, anxiety-related behavior, and total antioxidant capacity [TAC] were assessed. Depression and anxiety-like behavior were evaluated by the forced swimming test [FST] and elevated plus-maze, respectively

Results: The acute combined administration of Zn, Mg, and Vit B[1] significantly decreased immobility time in FST, increased the percentage of both time spent in-and entries to open arms in the elevated plus-maze, and augmented TAC

Conclusion: Our data suggest that acute administration of combined treatment with Zn, Mg, and Vit B[1] on postpartum day 3 improves depressive symptoms and anxiety-like behaviors. Our evaluation of TAC is in accordance with behavioral results

Reducing creatine kinase-MB levels following oxytocin administration during ischemia-reperfusion periods in isolated rat heart

Creatine kinase is a cardiac biomarker that is used for the assessment of ischemic injuries and myocardial infarction. The present study was designed to evaluate effects of oxytocin administration during ischemia and reperfusion periods on CK-MB levels in the coronary effluent of isolated rat heart and the possible role of oxytocin receptor, nitric oxide [NO], prostacyclin and mitochondrial ATP-dependent potassium channels in this regard. Male wistar rats [n=8] were anesthetized with sodium thiopental and their hearts were transferred to a Langendorff perfusion apparatus. All animals were randomly divided into nine groups as follow; in the ischemia-reperfusion group, hearts underwent 30 min of regional ischemia followed by 120 min of reperfusion. In oxytocin group, hearts were perfused with oxytocin 5 min after ischemia induction for 25 min. In other groups, 35 min prior to oxytocin perfusion, atosiban [a non-specific oxytocin receptor blocker], L-NAME [an NO synthase inhibitor], indomethacin [a non-specific cyclooxygenase blocker] and 5-HD [a specific mKATP channel blocker] were perfused for 10 min. In all groups, we measured CK-MB levels in the coronary effluent at the end of reperfusion. Moreover, coronary flow [mL/min] was measured at baseline, during ischemia period and 60 and 120 min after reperfusion. Oxytocin administration significantly reduced CK-MB level in oxytocin group as compared to ischemia-reperfusion group. Administration of atosiban, L-NAME, indomethacin and 5-HD prior to oxytocin perfusion abolished the effects of oxytocin on CK-MB levels. Administration of oxytocin during ischemia and reperfusion periods deceased CK-MB levels but infusion of atosiban, L-NAME, 5-HD and indomethacin inhibited oxytocin from exerting its effects

Acute effects of ruta graveolens L. on sperm parameters and DNA integrity in rats

Increase in world population is one of the serious and threatening issues in this century. Therefore, it is vitally important to find safe and effective contraceptive methods, especially for men which already have few choices in this regard. Medicinal plants that were used for contraception in ancient times could be good sources of investigation in this filed. Ruta graveolens L. is one the plants introduced in the Iranian traditional medicine as an oral male contraception to be used before intercourse. In this study we tried to investigate the probable effects of the plant on the spermatozoa of male rats. Ruta graveolens L. aqueous extract [5 g/kg] was administered orally to five groups of male rats and sperm motility was checked after half, one, two, four and six hours later. Moreover, one group of rats served as the control group. Subsequently, viability of cells [Eosin-Nigrosin staining], morphological changes [Diff-Quick staining], DNA status [acridine orange dye] and serum testosterone levels were assessed in the treated groups which had significant immotile spermatozoa. For statistical analysis, Student's t-test and one-way ANOVA with Tukey's post-hoc test were employed for comparison between groups. A significant reduction in sperm motility was seen one hour after administration of the extract in the case groups compared to the controls [36% vs. 68.15%, respectively, p<0.01]. The motility gradually increased afterwards, and by 6 hours, it was the same as the control group [65.43% and 68.15%, respectively]. No significant changes were seen in viability, morphology or DNA structure of spermatozoa in each group. Testosterone levels did not show any significant changes in the treated groups when compared with the controls. Since a significant temporary immobility of spermatozoa without any adverse effects on other sperm characteristics occurred upon the administration of Ruta graveolens L. aqueous extract, it seems that this plant might have the potential to be used for the suggested male contraception

Prooxidant-antioxidant balance and malondialdehyde over time in adult rats after tubal sterilization and vasectomy / 대한생식의학회지

OBJECTIVE: Sterilization (tubal sterilization and vasectomy) is a widely applied contraceptive method worldwide. Although most studies have described sterilization as a safe method, there are reports of tubal ligation (TL) and vasectomy complications. The aim of this study was to evaluate the effects of TL and vasectomy on the serum oxidative stress, specifically prooxidant-antioxidant balance (PAB) and malondialdehyde (MDA) levels, over time. METHODS: Male and female rats were classified into vasectomy, sham-vasectomy, TL, and sham-TL groups, respectively. The PAB and MDA levels were measured on days 15 and 45 and months 3 and 6 after the intervention. For female rats, blood sampling was performed during the diestrous phase and estradiol and progesterone were also measured. RESULTS: Serum PAB and MDA increased after TL (p<0.05). Vasectomy increased serum MDA remarkably after 45 days, 3 months, and 6 months (p<0.05). After vasectomy, serum PAB also increased although not significantly. Serum estradiol and progesterone decreased remarkably in the TL group compared to the sham group (p<0.05). CONCLUSION: Bilateral TL and vasectomy both increase the serum oxidative stress; however the imbalance after TL was very noticeable. As for the TL, the reduction of serum estrogen levels can be involved in this imbalance. Complications followed by TL or vasectomy could be due to increased levels of oxidants. Thus, prescribing antioxidants during and or after surgery may be a solution.

Postpartum depression and role of serum trace elements

Postpartum depression [PPD] is a major depressive disorder that most often emerges within 6 to 12 weeks of delivery, but can happen any time up to 1 year after birth. In developed countries, the incidence of postnatal depression is about 10-15% in adult women depending upon the diagnostic criteria, timing of screening and screening instruments used. Mothers with depressive symptoms have been found to have more complex behavioral contacts with their children; this situation can damage family relationships, and even leads to infanticide. Various pathophysiologies are proposed for postpartum depression: Nutritional deficiencies, iron deficiency anemia, rapid decrease in the levels of reproductive hormones following delivery, alterations in hypothalamic-pituitary-dernocortical mechanism and alterations in neurotransmitter levels. Among pathophysiologies of postpartum depression, the role of trace elements is highlighted. The purpose of this review is to assess the role of trace elements including zinc, magnesium, iron and copper in PPD. Zinc as a trace element has the second highest concentration of all transition metals in the brain, and its deficiency is associated with behavioral disturbances. Lower zinc blood concentration was found in women with postpartum depression. Another trace element, magnesium, also influences the nervous system via its actions on the release and metabolism of neurotransmitters. Various studies have focused on antidepressant-like effects of magnesium and its deficiency has been reported in depression. Depletion of magnesium stores during pregnancy is hypothesized to be the cause of postpartum depression. Iron deficiency is the most common single nutrient deficiency in the world. There is an association between anemia and depressive disorders. Copper has been recognized as an essential element for many years. Iron also plays a vital role in neurological disorders and its levels are relevant to postpartum depression. Involvement of trace elements can be seen in pathophysiologies of PPD in different ways. Therefore, trace element supplementation can be an alternative treatment for patients with PPD