Use of nanoparticles in animal models for prostate cancer treatment: a systematic review

Purpose: To conduct a systematic review of nanoparticles' use in the treatment of prostate cancer in animals. Methods: A systematic review was conducted in the databases PubMed, Scientific Electronic Library Online (SciELO), Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane Library, and EMBASE, and the descriptors were chosen based on terms indexed in Health Sciences Descriptors (DeCS)/Medical Subject Headings (MESH), which are: nanoparticles, nanomedicine, and prostate cancer. The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with ID CRD42021271008. Results: A total of 3,897 articles was chosen; after reading the inclusion and exclusion criteria, six scientific articles with themes involving nanoparticles carrying medications were reached. Among the nanoparticles found, there were carboxymethylcellulose polymer, micellar casein nanoparticles, liquid crystal nanoparticles, serum albumin nanoparticles, and poly(ethylene glycol)-block-polylactide (mPEG-PLA) conjugated nanoparticles encapsulating cabazitaxel, docetaxel, and flutamide, which were nanoparticles used to treat prostate cancer in animals. Conclusions: Through using nanoparticles to encapsulate medications for treating prostate cancer in animals, studies show a decrease in weight and tumor reduction, with nanoparticles resulting in greater survival time than free medications. The improved permeability and retention effect of nanoparticles in the bloodstream contribute to their effectiveness.

The effect of aerobic and resistance exercise on the progression of colorectal cancer in an animal model

Purpose: The aim of this study was to assess the effects of resistance and aerobic exercise on colorectal cancer (CRC) development in mice induced by azoxymethane (AOM) coupled with colitis. Methods: Forty animals induced with CRC were used, divided into five groups of eight animals each: sedentary; continuous aerobics; continuous anaerobic; aerobic PI; and anaerobic PI. AOM was administered to the animals in two doses of 10 mg/kg each over the course of two weeks, the first dose administered in the third week and the second administered in the fourth. For the colitis, three cycles of dextran sodium sulfate were administered for five days, separated by two weeks of water. The 14th week of the experiment saw the euthanasia, the removal of their colons, and the creation of microscopy slides for histological analysis. Results: Preneoplastic lesions developed in all five groups; there were no significant differences between them. However, in terms of inflammatory symptoms, mucosal ulceration was much more frequently in the exercise groups than in the sedentary group (p = 0.016). The number of polyps overall (p = 0.002), the distal region's polyp development (p = 0.003), and the proximal region's polyp development (p = 0.04) were all statistically different than sedentary group. Conclusions: The study discovered no significant difference in disease activity index scores between groups, but there was a significant difference in the number of polyps and the presence of mucosal ulceration in the colon.

Use of cyanoacrylate-based surgical adhesives associated to the macroporous tape in skin synthesis in rats

Abstract Purpose: To compare the use of new cyanoacrylate surgical adhesive associated with macroporous tapes in cutaneous synthesis. Methods: Male Wistar rats with a longitudinal incision of 4cm were used on the back, divided into four groups: GI used octyl-cyanoacrylate (Dermabond®), GII used N-2-butylcyanoacrylate, GIII used octyl-cyanoacrylate and macroporous tape and GIV used N-2-butyl cyanoacrylate and macroporous tape. On the fourteenth day, the rats were submitted to euthanasia, were divided in two parts, and a layer of skin subcutaneous tissue through an area of operative healing was removed. One part was submitted to the study of rupture strength with the use of tensiometer, and in the other part histological examination was performed. Results: No force test was similar between groups I and II, being different from groups III and IV (P <0.001), which were identical to each other (P> 0.05). The units were compared among the studied groups, and they were different with the use of macroporous tapes (P> 0.05). Conclusions: The purpose of macroporous tapes is associated with CA adhesives in cutaneous tissues that provide more resistant scars. The use of a combination of macroporous tapes leads to complete re-epithelialization, without provoking foreign body reaction, has hemostatic properties and does not cause an absorptive reaction.

Oxidative stress effects in the uterus, placenta and fetus of pregnant rats submitted to acute and chronic stress

Abstract Purpose: To evaluate the effects of oxidative stress in pregnant rats submitted to acute and chronic stress, relating to alterations in the uterus, placenta and fetus. Methods: Twenty-four female Wistar albino (Rattus norvegicus), were divided into four groups, for induction of oxidative stress the animals were submitted to cold and physical immobilization. Plasma fasting glucose and MDA were determined in all groups and the fetuses and placentas were measured. Results: There were no statistical differences in the levels of malonic dialdehyde (MDA), however the averages of chronic stress group were higher compared to control groups, which could explain the observed adverse effects; there was no correlation between puppies' size, the weight of the placenta and MDA values. Conclusions: Chronic stress causes adverse effects, when compared to control groups; chronic stress group had fetuses, placentas and number of puppies, significantly lower compared to other groups. The rats exposed to chronic stress, also presented a higher frequency of fetal resorption.

The aplication of cyanoacrilate surgical glue on skin suture in rats

Abstract Purpose: To compare the use of a new cyanoacrylate-based surgical glue and suture with sepa-rate points in skin wounds closure. Methods: Thirty-six rats were subjected to a 4cm dorsal longitudinal incision. Twelve were sub-jected to simple suture with polyamide 6-0, 12 rats underwent wall synthesis using Dermabond(r) and 12 was performed cutaneous synthesis with N-2-Butyl-Cyanoacrylate. Twelve of each group was euthanized on the seventh postoperative day, their blood was taken to biochemical tests and a layer of skin and subcutaneous tissue surrounding the surgical scar was randomly divided in two segments, to the submission of tension tests and to histological study. Results: There were no significant difference between groups (p>0.05). In the soft dermis there was more type I collagen production in group I (p<0.05), group II and III was similar re-sults (p>0.05). In the compact dermis, all 3 groups showed similar results (p>0.05). The biomechanical study was similarity between the glue groups (p>0.05) but the group III proved to be different from the others having a higher resistance (p>0.05) . Conclusion: This glue does not cause any inflammation or kidney and hepatic toxicity. Polyamide sutures are more resistant and the glue should be used alone only in less tension are-as.

Pentoxifylline and prostaglandin E1 action on ischemia and reperfusion of small intestine tissue in rats. An immunohistochemical study

PURPOSE: To investigate the action of pentoxifylline (PTX) and prostaglandin E1 (PGE1) on ischemia and reperfusion of small intestine tissue in rats, using immunohistochemical analysis. METHODS: Thirty-five Wistar rats were distributed as follows: group A (n=10): subjected to intestinal ischemia and reperfusion for 60 min, with no drugs; group B (n=10): PTX given during tissue ischemia and reperfusion; group C (n=10): PGE1 given during tissue ischemia and reperfusion; group D (n=5): sham. A segment of the small intestine was excised from each euthanized animal and subjected to immunohistochemical examination. RESULTS: Mean number of cells expressing anti-FAS ligand in the crypts was highest in Group A (78.9 ± 17.3), followed by groups B (16.7 ± 2.8), C (11.3 ± 1.8), and D (2.5 ± 0.9), with very significant differences between groups (p<0.0001). CONCLUSIONS: The use of pentoxifylline or prostaglandin E1 proved beneficial during tissue reperfusion. The immunohistochemical results demonstrated a decrease in apoptotic cells, while protecting other intestinal epithelium cells against death after reperfusion, allowing these cells to renew the epithelial tissue. .

Histopathological evaluation of tumor necrosis and volume after cyanogenic chemotherapy

PURPOSE: To determine the percentage of tumoral necrosis and volume after cyanogenic chemotherapy. METHODS: Histopathological findings of 20 Swiss mice inoculated subcutaneously in the left abdominal wall with 0.05 ml of cell suspension containing 2.5 x 105 viable cells of the Ehrlich tumor were evaluated. The tumor response to cyanogenic chemotherapy was determined using a system that comprises two inhibition factors of tumor growth by calculating the percentage of necrosis in the tumor tissue and calculation of tumor volume in treated animals relative to that in control animals. The importance of this system has been validated by the correlation between tumor inhibition in the groups treated with the respective percentages of necrosis. RESULTS: While the control group presented an average of 13.48 ± 14.71% necrosis and average tumor volume of 16.18 ± 10.94, the treated group had an average of 42.02 ± 11.58 and 6.8 ± 3.57, respectively. The tumor inhibition was significantly associated with treatment (p=0.0189). The analysis of necrosis percentage showed a significant prognostic importance (p=0.0001). CONCLUSION: It is concluded that the effect of cyanogenic chemotherapy showed strong inhibitory action of tumor growth, as well as an increase in its area of necrosis. .

Sulfane sulfur deficiency in malignant cells, increasing the inhibiting action of acetone cyanohydrin in tumor growth

PURPOSE: To demonstrate the irreversible poisoning action of the acetone cyanohydrin (AC) in malignant cells. METHODS: Thirty male Swiss mice were inoculated with 1x10³ Ehrlich tumor (ET) cells. The mice were divided into three groups (n=10): CG (saline); ACG1 (1.864 mg/Kg of AC) and ACG2 (2.796 mg/Kg of AC), treated every 48 hours from day 3 until day 13. On day 15 the mice were euthanized and the number of viable cells in ascites was determined. In the meantime, ET cells were incubated with AC (0.5, 1.0, 2.0 μg/mL). Cell viability and percentage of growth inhibition (PGI) were checked after one, two, three, four, 18 and 24 hours. RESULTS: There was reduction in volume and number of viable cells in ACG1 and ACG2 compared to CG. In ACG1 one of the animals did not present ascites. In ACG2 two mice did not present ascites and in CG none of the mice present ascites. The action of AC was dose and time dependent and there was no significant difference among the three doses. CONCLUSION: The acetone cyanohydrin promoted reduction of the tumor and also prevented tumor development in 20% of the treated animals.

Expression of FAS ligand in the ipsilateral and contralateral testicles of rats subjected to the torsion of the unilateral testicular cord

PURPOSE: To investigate the expression of FAS ligand (FASL) in ipsilateral and contralateral testicles of rats submitted to ischemia/reperfusion. METHODS: Wistar rats (n=21) distributed into groups control (GC), n=5, testicular exposure; ischemia (GI), (n=8), Torsion in the left testicular Cord (TCT) for three hours followed by orchiectomy without distortion and orchietomy of the contralateral testicle after 24 hours; and reperfusion (GR), (n=8), left TCT for 3 hours and distortion and repositioning on the scrotum and bilateral orchiectomy after 24 hours. Quantification of the FASL expression by immune-histochemistry. RESULTS: Statistical analysis showed similarity between GC and GI (p>0.05), differences detected are concentrated on the GR (p<0.05), increase in immunoexpression of FASL in the subgroups Right GR (406.8+-61.5) and Left GR (135.3 +-28.9) with significant predominance in the GR subgroup. CONCLUSION: Ischemia/reperfusion increased the FASL expression significantly in contralateral testicles in GR, in rats.

Estudo da ação antineoplásica da Tabebuia avellanedae (Ipê-Roxo) na carcinogênese induzida pelo azoximetano em camundongos / Study of the antineoplastic action of Tabebuia avellanedae in carcinogenesis induced by azoxymethane in mice

PURPOSE: To study the antitumor action of Tabebuia avellanedae in experimentally induced colon carcinogenesis by azoxymethane in mice. METHODS: Fifty (n=50) mice were divided into five groups: in group I azoxymethane (AOM) was administered, in Group II - β-lapachone, in group III - vehicle (diluent) and in group IV - vehicle + AOM and finally in group V - β-lapachone + AOM. RESULTS: It was observed the presence of aberrant crypt foci in all animals of groups I and IV, 50 percent in group II and 90 percent in group V. CONCLUSION: The β-lapachone extracted from the Tabebuia avellanedae showed no protective effect of lesions induced by azoxymethane in colon of mice.

OBJETIVO: Estudar a ação antitumoral da Tabebuia avellanedae (Ipê-Roxo) na carcinogênese colônica induzida experimentalmente pelo azoximetano em camundongos. MÉTODOS: Foram utilizados 50 camundongos divididos em 5 grupos: grupo I administrado Azoximetano (AOM); grupo II - β-lapachona; grupo III - veículo (diluente); grupo IV - veículo + AOM; e grupo V - β-lapachona + AOM. RESULTADOS: Observou-se presença de focos de criptas aberrantes em todos os animais dos grupos I e IV, 50 por cento no grupo II e 90 por cento no grupo V. CONCLUSÃO: A β-lapachona extraída da Tabebuia avellanedae não apresentou efeito protetor das lesões induzidas pelo azoximetano em cólon de camundongos.

Evaluation of acetone cyanohydrin effect in "in vitro" inativation of the Ehrlich ascites tumor cells / Avaliação do efeito de acetona cianidrina na inativação de células do tumor ascítico de Ehrlich "in vitro"

PURPOSE: To evaluate the antitumor effect of acetone cyanohydrin in Ehrlich ascites tumor cells in vitro. METHODS: The Ehrlich ascites tumor cells and lymphocytes were incubated with different concentrations of acetone cyanohydrin (0, 0.5, 1.0, 2.0, 10.0, 20.0 and 30.0 μg.mL-1), After 1, 2, 3, 4, 18 and 24 hours cell viability tests were performed by the trypan blue method. RESULTS: The results demonstrated a dose-dependent cytotoxic effect against the cells of Ehrlich ascites tumor. The concentrations of 20 and 30 μg.mL-1 was 100 percent of cell death in only 1 and 2 hours respectively. In lower doses of 0.5, 1.0 and 2.0 μg.mL-1 the cytotoxic effect was less intense, increasing gradually with time. CONCLUSIONS: At low concentrations of 0.5, 1.0 and 2.0 μg.mL-1, more than 90 percent of cell death was observed only after 24 hours of incubation which is the evidence that the tumor cell has the ability to poison cumulatively and irreversibly itself with the acetone cyanohydrin when compared with the results presented by human lymphocytes that the same doses and at the same time of incubation reached a maximum of 30 percent of cell death, suggesting an activity of rhodanese differentiated between the two cells.

OBJETIVO: Avaliar o efeito antitumoral da acetona cinidrina em células do tumor ascítico de Ehrlich in vitro. MÉTODOS: Células do tumor ascítico de Ehrlich e linfócitos foram incubadas com diferentes concentrações de acetona cianidrina (0, 0,5, 1,0, 2,0, 10,0, 20,0 e 30,0 μg.mL-1), depois de 1, 2, 3, 4, 18 e 24 horas foi verificada a viabilidade celular atravéz do método de azul de trypan. RESULTADOS: Os resultados demonstraram um efeito citotóxico dose dependente frente as células do tumor ascítico de Ehrlich. Nas concentrações de 20 e 30 μg.mL-1 ocorreu 100 por cento de morte celular em apenas 1 e 2 horas respectivamente. Nas doses mais baixas de 0,5, 1,0 e 2,0 μg.mL-1 o efeito citotóxico foi menos intenso, aumentando gradativamente com o tempo. CONCLUSÕES: Nas concentrações baixas de 0,5. 1,0 e 2,0 μg.mL-1, foi observado mais de 90 por cento de morte celular somente após 24 horas de incubação o que evidência a capacidade da célula tumoral de se intoxicar de maneira irreversível e acumulativa com a acetona cianidrina, quando comparadas com os resultados apresentados pelos linfócitos humanos que nas mesmas doses e nos mesmos tempos de incubação atingiram um máximo de 30 por cento de morte celular, o que sugere uma atividade de rodanase diferenciada entre as duas células.