Comparing the efficacy of dextrose, mannitol, and saline solutions in male rabbits' chemical castration

Effect of castration on acetyl salicylic acid metabolism in rabbits

Aim: to investigate the sub chronic toxicity of thiamethoxam on some parameters of reproductive performance in adult male rabbits including gene expression of LDH-C4, FSHβ and LHβ and GnRHR.
 Method: sixteen adult male Chinchilla rabbits were divided into two equal groups. Animals in the first group were treated orally with TMX at dose of 250 mg/kg body weight for 90 days. The second group was served as control.
 Result: Obtained results showed that TMX increased the relative weight of some reproductive organs including testis and prostate. Hormonal analysis revealed that, TMX induced a significant elevation in the serum testosterone level, while the concentrations of FSH and LH hormones did not exhibit any alterations between treated and control groups. In addition, LDH-C4, FSHβ and LHβ and GnRHR genes were down regulated in TMX treated group.
 Conclusion: Administration of thiamethoxam for 90 days in male rabbits induced a noticeable adverse effect on serum testosterone level and down regulated genes related to male rabbit reproductive performance.

Diabetes in a long period can damage the testicular tissue and impair the male fertility potential. Recently, different herbal treatments have been used for the prevention of type I diabetes and its pathological effects. Methanolic extract of Equisetumarvense has anti-oxidant and hypoglycemic properties. Thus, the current study aimed to evaluate the protective effects of Equisetum arvense methanolic extract (EE) on diabetes-induced detrimental effects in mice testicular tissue. Thirty-two adult male mice were randomly divided into four groups including control-sham, diabetic (induced by streptozotocin, 50.00 mg kg-1 for five days), diabetic + EE 250 (250 mg kg-1) and diabetic + EE 500 (500 mg kg-1). After 45 days, all animals were euthanized and their testicles were dissected out and undergone histological analyses. Moreover, the serum level of testosterone was evaluated. Analyses showed that seminiferous tubules diameter, Leydig cells number per mm2 of the connective tissue, Sertoli cells number per tubule, serum level of testosterone and percentage of seminiferous tubules with positive tubular differentiation, repopulation and spermiogenesis indices were significantly decreased in the diabetic group in comparison with control-sham group. The administration of EE in test groups significantly decreased the adverse effects of diabetes (especially 500 mg kg-1). The results of this study revealed that diabetes disturbs spermatogenesis and spermiogenesis processes in mice. Meanwhile, the EE prevents diabetes-induced damages in mice testicular tissue, which may be associated with its hypoglycemic and antioxidative activities.

Background: Exposure to ionizing radiation, particularly X-rays, induces harmful effects on radiosensitive tissues such as the male reproductive system through the generation of reactive oxygen species, resulting in oxidative stress, DNA damage, and cellular degeneration. These alterations negatively affect spermatogenic cells and Leydig cell function, leading to impaired spermatogenesis and decreased testosterone production. Folic acid, an essential B vitamin involved in DNA synthesis, repair, and antioxidant defense, has been proposed as a potential radioprotective agent. This study aimed to evaluate the radioprotective effects of folic acid on testicular tissue and serum testosterone levels in male rabbits exposed to X-ray irradiation. Materials and Methods: Twenty adult male rabbits were randomly assigned to four equal groups (n = 5): control, folic acid–treated (0.07 mg/kg body weight orally for one month), X-ray–exposed (80 kV, distance 98 cm, once daily for one week), and a folic acid plus X-ray group in which animals received folic acid for one month prior to irradiation. Clinical signs and body weight were monitored throughout the experiment. Serum testosterone levels were measured using ELISA, and testicular tissues were collected for histopathological examination following hematoxylin and eosin staining. Statistical analysis was performed using one-way ANOVA with significance set at P ≤ 0.05. Results: X-ray exposure caused a significant reduction in serum testosterone levels and induced marked histopathological alterations, including edema, necrosis of spermatogenic cells, reduced germinal layers, and oligospermia. In contrast, folic acid administration, either alone or prior to irradiation, maintained testosterone levels near normal values and markedly reduced testicular damage. Pretreated rabbits exhibited preservation of seminiferous tubule architecture and improved cellular integrity. Conclusion: These findings indicate that folic acid exerts a significant protective effect against X-ray–induced testicular injury and may serve as a supportive strategy to mitigate radiation-induced reproductive toxicity when used within approved therapeutic doses.

Metabolism of adrenal androgen and its impacts on prostate cancer after castration

Background: Neurokinin B is a regulator of puberty and reproduction, however its chronic effects on gonads in adult male mammals remain elusive. Objectives: To investigate potentials of variable doses of Neurokinin B on histomorphology of testicular tissue and serum testosterone levels in adult rabbits. Material and Methods: This Laboratory based experimental study was conducted at Gomal Centre of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, Pakistan from June-2019 to June-2020. Adult male New Zealand white rabbits (n=18) with an average weight of 1.52kg were randomly assigned to three groups. Study animals were administered subcutaneously with Neurokinin B in two variable doses: 1 µg and 1 çg. Control rabbits were injected with distilled water. After 12 days of continuous peptide treatment, animals (n=06) in each group were sacrificed. Testicular tissues were dissected and processed for light microscopy. Blood collection was performed directly from left ventricle, serum was separated and assayed for testosterone by enzyme linked immunosorbent assay.Results: Neurokinin B did not alter the body weight of experimental rabbits as compared to control. No significant change on testicular weight, testicular volume and gonadosomatic index was observed at any dose of Neurokinin B. Seminiferous tubular diameter (µm) increased non-significantly while seminiferous epithelial height (µm) increased significantly in high dose group as compared to control group. Serum testosterone concentration increased significantly (P?0.01) at both low (1çg) and high (1µg) doses of Neurokinin B as compared to control.Conclusion: Continuous administration of Neurokinin B effect positively on serum testosterone and testicular morphology.Keywords: Histomorphology, Neurokinin B, Tachykinins, Testes, Testosterone

Simple SummaryMedical castration is the most frequent form of androgen deprivation therapy given as primary treatment for hormone-sensitive metastatic prostate cancer (PCa) and as neo-adjuvant treatment in radiation therapy for intermediate and high-risk localised and locally advanced PCa. PCa guidelines recommend determining serum testosterone levels during castration to assess its efficacy and define castration resistance. Some studies suggest other biochemical serum compounds may assess the effectiveness of castration, such as free testosterone and luteinising hormone (LH). This systematic review aims to analyse the current evidence of biochemical candidates to properly assess medical castration efficacy. We found low-quality evidence supporting the current method to measure serum testosterone during medical castration. All reported studies used immunoassays to quantify the serum testosterone levels of men undergoing medical castration instead of the appropriate liquid chromatography with tandem mass spectrometry (LC-MSMS) to measure low testosterone concentrations. Longitudinal studies are needed to analyse the prognostic value of the serum testosterone measured with LC-MSMS and measure serum-free testosterone or LH.Measuring serum testosterone determination during medical castration is recommended by prostate cancer (PCa) guidelines to assess its efficacy and define castration resistance. It has been suggested that other biochemical compounds, such as free testosterone or luteinising hormone (LH), could also assess castration efficacy. We aimed to analyse the current evidence for serum biochemical compounds that could be appropriate candidates for evaluating medical castration efficacy. A systematic review was conducted after two investigators independently searched the literature in the PubMed, Cochrane Library, and EMBASE databases published between January 1980 and February 2023. Their searches used the medical subject headings ‘prostatic neoplasms’, ‘testosterone and androgen antagonists’, ‘gonadotropin-releasing hormone/analogues and derivatives’, ‘free testosterone’, and ‘luteinising hormone’. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, and their eligibility was based on the Participants, Intervention, Comparator, and Outcome strategy. The search was limited to original articles published in English. Among the 6599 initially identified titles, 15 original studies analysing the clinical impact of serum testosterone levels in PCa patients undergoing androgen deprivation therapy (ADT) were selected for evidence acquisition. The risk of bias in individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All selected studies used immunoassays to measure serum testosterone, although only methods based on liquid or gas chromatography and mass spectrometry are recommended to measure low testosterone concentrations. The reported series were not uniform in clinical stage, ADT types, and the time or number of serum testosterone measurements. Only some studies found low serum testosterone levels (<20 or <32 ng/dL) associated with greater survival free of biochemical progression and castration resistance. We conclude that little current evidence justifies the measurement of serum testosterone during ADT using no appropriate methods. No reported longitudinal studies have examined the clinical impact of serum testosterone measured using liquid chromatography with tandem mass spectrometry (LC-MSMS), free testosterone, or LH in PCa patients undergoing medical castration. We conclude that well-designed longitudinal studies examining the clinical impact of serum testosterone measured with LC-MSMS, serum-free testosterone, and LH on biochemical progression and castration resistance in PCa patients undergoing neo-adjuvant castration in radiation therapy or continuous castration are needed.

The Effects of Medical Castration on Testes in Patients With Advanced Prostate Cancer

The current study was conducted to investigate the ameliorative effect of moderate-intensity exercise training insole and simultaneous with insulin on diabetes (DM)-induced pathogenesis at the testicular tissue and sperm level. For this purpose, 36 mature male Wistar rats were divided into six groups, including sedentary control (Con), exercise training (EX), sedentary experimental DM-induced (SDM), exercise training+DM-induced (DM+EX), insulin-treated sedentary DM-induced (DM+INS) and exercise training and insulin-treated DM-induced (DM+INS+EX) groups. Following DM induction, the 6-week exercise training intervention (30min of moderate-intensity running on a treadmill, once daily [5days/week]) was considered in EX groups. The tubular differentiation (TDI) and spermiogenesis (SPI) indices, testicular total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPX) contents, serum testosterone and insulin levels, the apoptosis ratio and sperm parameters were assessed. The exercise in sole (EX) and simultaneous forms with INS (DM+INS+EX group) ameliorated the DM-suppressed spermatogenesis and spermiogenesis indices, up-regulated the serum testosterone and insulin levels, enhanced testicular SOD content, inhibited the apoptosis and improved almost all sperm parameters. In conclusion, exercise training, when simultaneously considered with insulin, fairly boosts the insulin-induced impacts, including the up-regulated testicular endocrine and antioxidant status, spermatogenesis and sperm quality.

Sexually mature male rabbits actively immunized against highly purified ovine LH (oLH) were used as a model system to study the effects of endogenous LH deprivation (and therefore testosterone) on spermatogenesis as well as pituitary FSH secretion. Immunization against oLH generated antibody titres capable of cross-reacting and neutralizing rabbit LH and this resulted in a significant reduction (P < 0.01) in serum testosterone levels by 2-4 weeks of immunization. A significant increase in circulating FSH concentration (from a basal level of approximately 1 ng to 60-100 ng/ml; P < 0.01) was observed within 4-6 weeks of immunization, perhaps a consequence of the negative feedback effect of the lack of testosterone. The effect of LH deprivation on spermatogenesis assessed by DNA flow cytometry and histological analyses of testicular biopsy tissue revealed that lack of testosterone primarily results in a rapid reduction and complete absence of round (1C) and elongated (HC) spermatids. The immediate effect of LH/testosterone deprivation thus appears to be at the step of meiotic transformation of primary spermatocytes (4C) to 1C. A significant reduction (> 80%; P < 0.01) in the 4C population and a relative accumulation (> 90%; P < 0.01) in spermatogonia (2C) was also observed, suggesting a need for testosterone during the transformation of 2C to 4C. In all but one of the rabbits, both qualitative and quantitative recovery in spermatogenesis occurred during the recovery phase, even at a time when only a marginal increase in serum testosterone (compared with the preimmunization) levels was observed as a result of a rapid decline in the cross-reactive antibody titres. These results clearly show that LH/testosterone deprivation in addition to primarily affecting the meiotic step also regulates the conversion of 2C to 4C during spermatogenesis.

The goal of this study was to investigate the effects of medical castration (luteinizing hormone-receptor hormone [LH-RH] agonist treatment) or surgical castration on erectile function in an animal model. New Zealand White male rabbits were either kept intact (control); surgically orchiectomized; or treated for 2, 4, or 8 weeks with the LH-RH agonist leuprolide acetate (107 microg/kg/mo). At 2 weeks, plasma testosterone levels of orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of intact control animals, respectively. Erectile function was assessed by continuously recording systemic arterial pressure (SAP) and intracavernosal blood pressure (ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at varying frequencies (2.5-32 Hz). Androgen deprivation by surgical (orchiectomy) or medical (leuprolide acetate) castration reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil (10 microg/kg) did not enhance ICP in surgically orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by surgical or medical castration. Further, Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. These data demonstrate that androgen deprivation achieved by surgical or medical castration adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.

The stability of ofloxacin was evaluated in 10 different infusion fluids under various storage conditions. Solutions of ofloxacin (0.4 mg/mL and 4.0 mg/mL) were prepared in (1) 0.9% sodium chloride injection; (2) 5% dextrose injection; (3) 5% dextrose and 0.9% sodium chloride injection; (4) 5% dextrose and lactated Ringer's injection; (5) 5% sodium bicarbonate injection; (6) Plasma-Lyte 56 and 5% dextrose injection; (7) 5% dextrose, 0.45% sodium chloride, and 0.15% potassium chloride injection; (8) 1/6 M sodium lactate injection; (9) water for injection; and (10) 20% mannitol injection. Each solution was injected into polyvinyl chloride bags and stored at (1) 24 degrees C for 3 days, (2) 5 degrees C for 7 days, (3) 5 degrees C for 14 days, (4) -20 degrees C for 13 weeks and then 5 degrees C for 14 days, or (5) -20 degrees C for 26 weeks and then 5 degrees C, for 14 days. Samples were assayed initially and after storage by high-performance liquid chromatography and examined for visual clarity, pH, turbidity, and particulates. Ofloxacin was stable in all solutions and under all storage conditions. All of the solutions were clear, pH was stable, and particulate-matter counts were acceptable under all storage conditions (except for the 20% mannitol solution, which formed crystals at 5 degrees C and -20 degrees C). An injectable formulation of ofloxacin was stable for at least 3 days at 24 degrees C, 14 days at 5 degrees C, and 26 weeks at -20 degrees C in all tested infusion fluids. Crystals formed in refrigerated or frozen solutions prepared with 20% mannitol injection.

The present work was performed to determine the effect of thalidomide exposure on reproductive function and early embryonic development. Twenty-five female New Zealand White rabbits were orally gavaged with 0, 10, 50, or 100 mg/kg/day thalidomide 14 days prior to mating through to gestation day 7 for a total of 22 days. Treated females were Caesarean-sectioned approximately 29 days after the date of attempted mating. Following mating with treated females, male rabbits (25/dose) were gavaged with 0, 30, 150, or 500 mg/kg/day beginning 14 days prior to mating with a group of untreated females (25/dose). Doses were administered through mating until the day before sacrifice for a minimum of 56 days. Untreated females were Caesarean-sectioned 29 days after the last attempted mating. Comprehensive necropsy and histopathology of the reproductive system were performed. Treated females had reduction in body weight gain during gestation. Mating and pregnancy parameters were unaffected by thalidomide. At 100 m/kg, litter averages for corpora lutea, implantations, litter sizes, does with viable fetuses and live fetuses decreased and the number of early resorptions, does with any resorptions, does with all conceptuses resorbed, and the percent resorbed conceptuses per litter increased. The number of early resorptions, the average number of early resorptions per litter, and the percent resorbed conceptuses per litter increased at 10 and 50 mg/kg. There were no thalidomide-related external fetal malformations. Mating and fertility in male rabbits were unaffected by thalidomide. There was an increased incidence of flaccid testes at 150 and 500 mg/kg and of bilateral small testes in all treated groups. At 500 mg/kg, there was degeneration of the germinal epithelium of the testicles with an increase in multinucleated giant cells in seminiferous tubule and a loss of round and elongating spermatids. Thalidomide had no adverse effects on mating and fertility in male and female rabbits dosed up to 500 and 100 mg/kg/day, respectively, for 14 days prior to mating. After 56 day of dosing, histopathologic changes with no associated sperm abnormalities were observed in the testicles. Embryonic development NOAEL for treated females mated to untreated males was <10 mg/kg. Corresponding fertility NOAEL for treated males mated to untreated females was 500 mg/kg.

The effects of surgical and medical castration on bone mineral density (BMD) were compared in men receiving castration therapy as a result of prostate cancer. A control group of men of similar age was also included in the study. A total of 28 men with prostatic cancer who had been selected to undergo medical or surgical castration and 10 healthy men with benign urological disorders were followed from baseline observations and BMD was assessed at 3, 6, 12 and 36 months. Serum hormone levels were also assessed. Orchidectomy and treatment with gonadotrophin-releasing hormone (GnRH) analogues caused an expected rapid decrease in serum testosterone levels, with no difference between these two groups. The mean loss of BMD in the femoral neck measured by means of dual-energy X-ray absorptiometry in surgically castrated men and GnRH-treated men was 0.037 g/cm2 (4.53%; SEM 0.013 g/cm2; p = 0.010) and 0.027 g/cm2 (3.18%; SEM 0.014 g/cm2; p = 0.119), respectively at 12 months, while the controls gained 0.017 g/cm2 (1.26%; SEM 0.013 g/cm2; p = 0.195). In the heel, surgically castrated men lost 9.04% of BMD (p < 0.001), the GnRH-treated men lost 3.58% (p = NS) and the controls gained 1.26% (p = NS). We found a more pronounced decrease in BMD in men with metastatic prostate cancer who were treated with surgical castration than in those who were treated with GnRH analogues.

Differential effects of Renografin-76 on the ischemic and nonischemic myocardium