scholarly journals Synergistic Effect of Docetaxel Plus Saponin Fraction of Vitex doniana on Prostate Specific Antigen and p53 in Nitrsobis (2-oxopropyl) Amine-induced Prostate Toxicity

Author(s):  
Ifeanacho Ezeteonu Abireh ◽  
Godson Emeka Anyanwu

Aim: This study investigated the synergistic effect of docetaxel plus saponin fraction of Vitex doniana on prostate specific antigen and p53 in nitrsobis (2-oxopropyl) amine-induced prostate toxicity in Wistar rat. Methodology: Twenty-four (24) male Wistar rats with elevated serum prostate specific antigen level were selected from a group of sixty (60) rats pretreated with subcutaneous Nitrosobis (2-oxopropyl) amine 5 mg/kg daily for 4 weeks. The selected 24 male Wistar rats were then grouped into 6 groups of four (4) rats each. Group 1 was given 1ml normal saline daily from day 1-28. Groups 2, 3, 4, 5, and 6 further received subcutaneous nitrosobis (2-oxopropyl) amine 5 mg/kg daily from day 1-28. In addition, groups 3, 4, 5, and 6 were given weekly intravenous docetaxel 8 mg/kg on day 15 and 22. In addition to docetaxel, groups 4, 5, and 6 were further treated with oral saponin at 250 mg/kg, 500 mg/kg, and 750 mg/kg, respectively, daily, from day 15-28. Immunoenzymometric assay method was used for analysis of blood sample for prostate specific antigen. The prostate tissues were subjected to immuno study using the ImmunoCruz Staining System (Lab Vision Corporation, Fremont, CA, USA). The quantitative evaluation of p53 was done by calculating the percentages of p53-immunostained nuclei (labeling index). Results: Significant increase in prostate specific antigen and p53 expression were observed in group 2 (treated with Nitrsobis (2-oxopropyl) amine alone) when compared with group 1 (control). Dose dependent decrease in prostate specific antigen and p53 expression were observed in groups 4, 5, and 6, treated with docetaxel 8 mg/kg plus 250 mg/kg, 500 mg/kg, and 750 mg/kg of saponin respectively. Conclusion: Docetaxel plus Saponin fraction of Vitex doniana significantly reduced the serum prostate specific antigen concentration and p53 expression in a dose dependent manner, with the group treated with 750 mg/kg showing the highest decrease in the parameters tested.

2014 ◽  
Vol 31 (02) ◽  
pp. 075-081
Author(s):  
A. Akinlolu ◽  
O. Akinola ◽  
P. Khobe ◽  
K. Obasi ◽  
O. Dada

Abstract Introduction: AAzathioprine and Methotrexate are both used in the treatment of cancer; and are classified as cytotoxic drugs with reported adverse effects such as oxidative damage to the DNA/RNA, the testes and sperm cells. This study, therefore, tested the hypothesis that AAzathioprine and Methotrexate administrations impair the morphology and functions of the testes in adult male wistar rats. Methods: AAzathioprine (50-150mg per day) and Methotrexate (2.5mg per week) are used in the treatment of cancer in adult Man. We tested the hypothesis that AAzathioprine and Methotrexate impair the morphology and functions of testes in rats. Forty adult male wistar rats (150-230g) were employed in the study: Control Group I received physiological saline while Experimental Groups II - V received oral administrations of 5mg/kg/bodyweight of AAzathioprine per day, 15mg/kg/bodyweight of AAzathioprine per day, 8mg/kg/bodyweight of Methotrexate per week and 20mg/kg/bodyweight of Methotrexate per week respectively for 35 days. Results: Histological examinations of the testes of rats of Groups II - V showed dose-dependent morphological anomalies such as fewer collagen ibers of connective tissues, disrupted seminiferous tubules and scanty spermatozoa when compared to rats of Group I. Statistical analyses showed dose-dependent elevated levels (P≤0.05) of superoxide dismutase and malondialdehyde in testes homogenates of rats of Groups II - V when compared to rats of Group I. This implied increased oxidative stress in rats of Groups II - V. Evaluations of Follicle Stimulating Hormone and Testosterone showed dose-dependent significantly elevated levels (P≤0.05) in rats of Groups II - V when compared to rats of Group I. Conclusions: Our findings are consistent with the stated hypothesis.


1985 ◽  
Vol 1 (S1) ◽  
pp. 186-188
Author(s):  
T. Orlowski ◽  
S. Chabielski ◽  
A. Badowski ◽  
Z. Dumanski

The pathology of mixed injuries resulting from simultaneous action of several damaging factors on the organism is still insufficiently known. Peritonitis is the most frequent complication of injuries to the abdominal organs. Co-existence of peritonitis with radiation sickness impairs considerably the results of therapeutic management and prognosis. Surgical treatment is indicated in the latent period of radiation sickness or only in the period of recovery. In the case of diffuse peritonitis, the time of performing the operation is of essential importance for the prognosis. Thepurposeof the reportedinvestigationswas the study of the effect of ionizing radiation before exposure of the organism on the course of diffuse peritonitis and a trial of prolonging with an antibiotic the preliminary stage of the disease in which surgical treatment is effective. Investigations were carried out on 160 male Wistar rats weighing 250g on the average, divided into five groups. Group 1 served as control. In Group 2, the rats were only exposed to radiation.


2006 ◽  
Vol 14 (4) ◽  
pp. 238-241 ◽  
Author(s):  
Juliane Guimarães de Carvalho ◽  
Rodrigo Cardoso de Oliveira ◽  
Marília Afonso Rabelo Buzalaf

OBJECTIVE: This study evaluated the use of plasma, bone surface (periosteal) and whole bone as biomarkers of chronic fluoride (F) exposure. METHODS: Forty male Wistar rats were assigned to 4 groups (n=10/gr) that differed according to the F concentration they received in the drinking water. Groups 1, 2, 3 and 4 received water containing 0 (control), 5, 15, and 50 mg F/L, respectively. The rats were killed at 120 days of age. Plasma and femur were collected and analyzed for fluoride with the ion specific electrode by the direct method or after hexamethyldisiloxane-facilitated diffusion. Data were tested for statistically significant differences by ANOVA and linear regression (p<0.05). RESULTS: Mean (± SE) plasma F concentrations ranged from 0.030 ± 0.002 to 0.187 ± 0.013 (mg/mL). The concentrations in surface and whole bone ranged from 610 ± 32 to 4,693 222; and 647 ± 22 to 3,439 ± 134 µg/g, respectively. The surface/whole F concentration ratios were 0.941, 1.414, 1.173 and 1.377, for groups 1, 2, 3 and 4 respectively. For plasma and whole bone, the difference among all groups was statistically significant, except for group 2 compared to group 1. For bone surface, all groups differed from each other except for group 2 compared to group 3. A significant positive correlation was found between bone surface and whole bone F (r²=0.94), as well as between plasma and bone surface (r²=0.71) and plasma and whole bone (r²=0.74). CONCLUSIONS: Data suggest that both bone surface and whole bone are suitable biomarkers of chronic F exposure in rats and plasma may be used as indicator of bone fluoride levels.


2009 ◽  
Vol 24 (3) ◽  
pp. 189-194 ◽  
Author(s):  
Frederico Theobaldo Ramos Rocha ◽  
Laercio Gomes Lourenço ◽  
Mário Jorge Jucá ◽  
Valéria Costa ◽  
Antenor Teixeira Leal

PURPOSE: To evaluate chemoprevention by celecoxib in cases of reflux-induced gastric adenocarcinoma, in Wistar rats that underwent gastrojejunostomy. METHODS: Sixty male Wistar rats of average age three months underwent surgery and were distributed into three groups: group 1, exploratory laparotomy; group 2, gastrojejunostomy; and group 3, gastrojejunostomy and daily celecoxib administration. After 53 weeks, the animals were sacrificed. Changes in the mucosa of the gastric body of group 1 and in the gastrojejunal anastomosis of groups 2 and 3, observed in histopathological and immunohistochemical examinations, were compared. All statistical analyses were performed using Epi-Info®, version 3.4.3. RESULTS: Comparison between groups 2 and 3 relative to the presence of adenocarcinoma showed a statistically significant difference (p=0.0023). Analysis of the association between groups 2 and 3 relative to COX-2 expression also showed a statistically significant difference (p=0.0018). CONCLUSION: Celecoxib had an inhibiting effect on gastric carcinogenesis induced by enterogastric reflux in an animal model.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 289-289
Author(s):  
Jason Homza ◽  
John T. Nawrocki ◽  
Harmar D. Brereton ◽  
Christopher A. Peters

289 Background: Salvage radiotherapy (SRT) may be employed as a potentially curative intervention for patients experiencing biochemical failure (serum prostate-specific antigen [PSA] ≥ 0.2 ng/mL) after prostatectomy for localized prostate cancer. Patients not showing a favorable response to SRT alone may require additional therapies and may benefit from earlier identification of this need. Methods: 131 consecutive patients received SRT during the timeframe of this study. 76 were deemed eligible based on the following criteria: prostatic adenocarcinoma diagnosis receiving SRT, no clinical evidence of metastasis, no hormone use prior to/during SRT, serum PSA measurement halfway through SRT, and minimum follow-up time of 3 months. Median follow-up time was 51.6 months. Eligible patients were divided into three groups based on PSA response by the midpoint of treatment: no change, decrease, or increase in PSA. The primary endpoint of the study was clinical failure (measured from SRT completion), defined as serum PSA value ≥0.2ng/mL above the post-radiotherapy nadir, initiation of androgen deprivation therapy, development of bone metastasis, or death from prostate cancer. Results: 13.1% experienced no change in PSA halfway through SRT (group 0), 68.4% of patients experienced a decrease (group 1), 18.4% experienced an increase (group 2). Four-year freedom from clinical failure was 60.0% for group 0, 58.3% for group 1, and 41.7% for group 2. Median time to clinical failure was 71.7 months for group 1, 26.8 months for group 2, and was not reached for group 0. Pairwise multiple comparison demonstrated a significant difference in four-year freedom from clinical failure between groups 1 and 2 (p = 0.036). Conclusions: These data strongly suggest that changes in PSA are apparent midway through SRT and are associated with 4-year freedom from clinical failure. Further study is warranted to determine whether mid-treatment PSA during SRT may be used to identify a subset of patients that may benefit from treatment intensification.


2018 ◽  
Vol 85 (2) ◽  
pp. 68-72 ◽  
Author(s):  
Denis Vladimirovich Chinenov ◽  
Leonid Mikhailovich Rapoport ◽  
Evgeniy Valerievich Shpot ◽  
Dmitry Victorovich Enikeev ◽  
Yaroslav Nikolaevich Chernov ◽  
...  

Aim: To evaluate early prostate cancer cryoablation functional and oncological results in comparison with results of extraperitoneoscopic radical prostatectomy. Materials and methods: We analyzed early results of surgical treatment of 285 patients with prostate cancer: 42 of them had undergone total cryoablation (Group 1) while the rest of them had been treated by radical laparo- and extraperitoneoscopic prostatectomy. For comparative assessment of prostate cryoablation results, 42 patients from Group 2 randomized in accordance with their age, stage of disease, Gleason, prostate-specific antigen, and prostate volume were selected. In compliance with the results of pre-surgical examination, all the patients had low oncological risk and were not concerned in sexual function. Volume of prostate was from 22 to 65 cm3, prostate-specific antigen level was from 4.1 to 10 ng/mL, and level of neoplastic process differentiation using Gleason grading system was from 6 to 7a (3 + 4) scores. Results: Patients after prostate cryoablation in early post-surgical period felt lower intensity of postoperative pain compared with those who had undergone prostatectomy. Follow-up period up to 12 months manifested significant true reduction of prostate-specific antigen level in both groups of patients. Frequency of stress-induced enuresis in Group 1 was not observed. Conclusion: Radical prostatectomy is still the traditional treatment of choice in the case of localized prostate cancer. But we can draw the conclusion that cryoablation is an effective low-invasive method for treatment of low oncological risk patients, which gives the opportunity both to achieve good oncological results and to preserve high life quality.


2019 ◽  
Vol 39 (9) ◽  
pp. 1133-1146 ◽  
Author(s):  
A Vafa ◽  
SM Afzal ◽  
P Barnwal ◽  
S Rashid ◽  
A Shahid ◽  
...  

Benign prostatic hyperplasia (BPH) is an important key health concern for aging men. Polyphenolic compounds have been found to possess important roles in the inhibition of numerous ailments that involve reactive oxygen species and inflammation. Diosmin is a citrus flavone that possesses antioxidant, anti-inflammatory, antiproliferative, and anticancer activities, so based on these properties of diosmin, we decided to evaluate its effect on testosterone propionate (TP)-induced BPH. A total of 30 Wistar rats were randomly assigned to five groups having six animals in each. This study was of 28 days in which TP (5 mg kg−1) was administered to induce BPH in the last 10 days of the study. It was found that diosmin at the doses of 20 and 40 mg kg−1 significantly reduced malondialdehyde and xanthine oxidase formation in a dose-dependent manner; however, it replenished catalase, glutathione (GSH), and GSH-dependent enzymes, that is, glutathione peroxidase, glutathione reductase, and glutathione- S-transferase significantly against TP-induced BPH. Further, immunohistochemical study showed that diosmin alleviated inflammatory markers (nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2, and interleukin-6). It was also found that diosmin downregulated the expression of androgen receptor and decreased the prostate-specific antigen concentration dose-dependently, significantly against TP-induced BPH. Diosmin also restored histoarchitecture of the prostate in a dose-dependent manner. Findings from the present study revealed the protective role of diosmin against TP-induced BPH in Wistar rats.


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