Pregabalin alters reproductive performance in male mice and causes congenital anomalies in offspring.

CONTEXT: Pregabalin is an anticonvulsant drug with analgesic activity for the treatment of neuropathic pain. AIMS: To valuate the toxicity of pregabalin in reproductive parameters, spermatogenesis, and teratogenicity in the offspring of mice. METHODS: Twenty male mice were randomly distributed into two groups: PGB group and group C (n =10 per group). The animals in the PGB group received, via gavage, 200mg/kg of pregabalin diluted in distilled water daily, for a period of 45days. Group C received distilled water under the same experimental design. KEY RESULTS: In the paternal parameters of the PGB group, there was a significant increase in the size of the testicles, morphological alterations in the spermatozoa, a decrease in the Johnsen score, an increase in the Leydig cells, and a decrease in the serum level of testosterone. In the intrauterine development parameters of females mated with males from the PGB group, a significant decrease in placental weight, weight and length of fetuses, and fetal viability rate was observed. There was a significant increase in the number of resorptions and post-implantation losses. The significant anomalies observed in the offspring were alteration in the size of the kidneys, absent metacarpals and phalanges, alteration in the sternum, and supernumerary thoracic vertebrae. CONCLUSION: Results suggest that pregabalin had toxic effects on the reproductive function of male mice and teratogenic potential. IMPLICATIONS: The findings of this study may provide new hypotheses, taking into account the risk-benefit ratio for male reproduction and offspring health.

Intrauterine exposure to omeprazole increases the risk of teeth morphological anomalies in the offspring of a murine model.

Conditions experienced in early life have long-lasting effects on offspring health. Despite this, little is known about how maternal exposure to drugs during pregnancy affects offspring teeth morphogenesis. In humans, omeprazole is a common drug used to mitigate Gastroesophageal Reflux Disease. Importantly, omeprazole is a non-specific proton-pump inhibitor, which may inhibit the proton pumps expressed in the developing tooth germ. To date, however, the effects of intrauterine life exposure to omeprazole on offspring tooth development remain unknown. In this study, we addressed this gap in a murine model. Pregnant female Swiss mice were exposed to daily doses of 40 mg/kg of omeprazole from the 5th to the 17th day of pregnancy and the effects of such exposure on offspring odontogenesis parameters such as morphological abnormalities, disruptions in the ameloblast and odontoblast layers and the presence of dentin matrix were measured. Omeprazole exposure significantly increased the prevalence (control: 21.6%; treatment: 60%; p = 0.001) and the risk (posterior mean and 95% credible interval; control: 0.230 [0.129; 0.347]; treatment: 0.593 [0.449; 0.730]) of offspring teeth morphological abnormalities, although there were no statistically significant effects of omeprazole exposure on other parameters of tooth development. These findings suggest that there are potential side-effects to offspring oral health of omeprazole use during pregnancy.

Clinical, radiographic, and genetic observations in 2 families with cleidocranial dysplasia.

The clinical, radiographic, and molecular alterations in 7 individuals belonging to 2 families with clinical characteristics of cleidocranial dysplasia (CCD) were investigated. The patients underwent karyotype and genetic sequencing examinations. Cytogenetic analysis did not demonstrate any alterations. The next-generation sequencing technique employed for the molecular analysis revealed sequence variations in the RUNX2 gene: c.568C>T (p.Arg190Trp) in exon 4 in family A and c.1205del (p.Pro402Argfs*82) in exon 9 in family B. Incomplete closure of anterior fontanels, hypoplastic clavicles, and dental changes were observed in all 7 patients. Uncommon clinical findings, such as partial hearing loss and bilateral clavicular agenesis, were noted in some patients. According to the literature consulted, this is the first time that the total absence of the pubic bone in a study subject is being reported. The variable expression among individuals of the same family and between families A and B suggests the absence of a genotype-phenotype relationship. Early diagnosis allows the dentist to minimize the effects of changes associated with CCD by monitoring and providing appropriate treatment, and the identification of genetic sequence variations enables appropriate family genetic counseling.

Methylphenidate effects on mice odontogenesis and connections with human odontogenesis.

The purpose of this study is to evaluate the effects of Methylphenidate exposure on mice odontogenesis and connect them by bioinformatics with human odontogenesis. Thirty-two pregnant Swiss mice were divided into treated group and control group, which received, respectively, 5 mg/kg of Methylphenidate and saline solution from the 5th to the 17th day of pregnancy. The mouse embryos tooth germs were analyzed through optical microscopy, and the data collected were analyzed statistically by Fisher's exact test. The presence and similarity of Methylphenidate-associated genes (Pharmgkb database) in both organisms and their interaction with dental development genes (AmiGO2 database) were verified on STRING database. Rates of tooth germ malformations were higher in treated than in control group (Control: 18; Treated: 27; p = 0.035). Mouse embryo malformations were connected with 238 interactions between 69 dental development genes with 35 Methylphenidate genes. Fourteen interactions for four Methylphenidate genes with four dental development genes, with human experimental data, were connected with mouse phenotype data. By homology, the interactions and conservation of proteins/genes may indicate similar outcomes for both organisms. The exposure to Methylphenidate during pregnancy affected odontogenesis in mouse embryos and may affect human odontogenesis. The study of malformations in mice, with a bioinformatics approach, could contribute to understanding of the Methylphenidate effect on embryo development. These results may provide novel hypotheses for further testing and reinforce the FDA protocol: as Methylphenidate is included in category C, its use during pregnancy should be considered if the benefits outweigh the risks.

Sentimento materno ao receber um diagnóstico de malformação congênita / Sentimiento de la madre al recibir diagnóstico de malformación / Maternal feelings at congenital malformation diagnosis

RESUMO: Este artigo objetiva analisar o sentimento materno ao receber um diagnóstico de malformação congênita do filho nos períodos: pré-natal, nascimento e primeira infância. O estudo foi realizado com mães de filhos com anomalia fetal, por meio de noventa e sete entrevistas, que continham perguntas sobre gravidez e percepção acerca do diagnóstico. Direcionado ao sentimento destacam-se as questões: 'Como você se sentiu ao receber o diagnóstico?', 'Qual o sentimento atual?', 'Como encontrou conforto?'. Para compreensão dos dados foi utilizada a análise qualitativa de conteúdo com base numa estrutura de categorias. O diagnóstico de malformação congênita desmitifica as expectativas maternas quanto ao futuro do filho, configurando um cenário de ansiedade, confusão, insegurança e múltiplos medos. O auxílio, seja da equipe multidisciplinar de saúde, religioso ou familiar, é importante para ajudar mães a reduzirem o impacto emocional do diagnóstico, além de auxiliar com as dificuldades iniciais em estabelecer o vínculo com o bebê.

RESUMEN: El objetivo de articulo es analisar el sentimiento de la madre al recibir, en los períodos pré-natal, nacimento y primera infância, el diagnóstico de malformación congênita de su hijo. Para ello fue realizado un estúdio con madres cuyos hijos son portadores de anomalia fetal, por medio de noventa y siete entrevistas, que contenían preguntas sobre el embarazo y sobre el impacto de conocer el diagnóstico del bebé. Direccionado al sentimiento materno, se destacan en él, los siguientes aspectos: 'Como usted se sentio al recibir el diagnóstico?', 'Cual es su sentimiento actualmente?', 'Como encontro consuelo?'. Para poder compreender mejor los datos fue utilizada una análisis cualitativa de contenido con base en una estructura de categorias. El diagnóstico de malformación congénita desmitifica las expectativas maternas em relación al futuro de su hijo, configurando un escenário de ansiedad, confusión, inseguridad e múltiples miedos. El auxílio, sea del equipo multidisciplinario de salud, religioso o familiar, es importante para ayudar a las madres a reduzir el impacto emocional producido por el conocimiento del diagnóstico, y además servir de auxilio en las dificuldades iniciales de establecer un vínculo con el bebé.

ABSTRACT: This article aims to analyze the maternal feelings about a congenital malformation diagnosis received before birth, immediately after birth, or in early infancy. This study was conducted with mothers whose children have congenital anomalies, based on ninety-seven interviews that included questions regarding pregnancy and the mothers' perspective on their child diagnosis. Regarding maternal feelings, the main questions were: 'How did you feel when you first heard the diagnosis?', 'How have you been feeling?', 'Where have sought comfort?'. Qualitative analysis was performed based on categories for data comprehension. Congenital malformation diagnosis breaks down the maternal expectations around the child's future, creating an environment full of anxiety, confusion, insecurity and multiple fears. The support of the multidisciplinary health team, religious and domestic is important to reduce the emotional impact suffered by the mothers after the diagnosis. It also helps the early difficulties in bonding with the baby.

Processo de humanização na graduação: percepção do acadêmico do curso de medicina / Humanization process in undergreduation courses: perception of the medical student

O processo de humanização em formação médica é fundamental para o desenvolvimento de profissionais capacitados a assistirem ao paciente de forma digna, pautado na ética e empatia. O estudo, de caráter transversal e quantitativo, avaliou a percepção de estudantes de medicina de uma instituição pública do Paraná sobre o processo de humanização durante sua formação acadêmica. Os dados foram analisados por frequência relativa IC 95%. Revelou-se que 74,6% dos estudantes consideram que a sua formação contribua para a prática médica humanizada e que grande parte deles possui domínio sobre o conceito de determinação social do processo saúde e doença. Contudo, a metade deles não se considera apta a lidar com um dilema ético e moral. Embora haja um grande conhecimento sobre a humanização ao longo da graduação, ainda se faz necessário um aprimoramento da abordagem de assuntos relacionados à bioética e aos diversos fatores que interferem no processo saúde e doença.

Damage caused by exposure to propofol during gestation of mice / Danos causados pela exposição ao propofol durante a gestação em camundongos

Literature shows that surgical procedure could be necessary at any stage of pregnancy and can cause adverse effects on the mother and fetus. One of the most used anesthetics in surgical centers is propofol however; the safety during pregnancy has not been completely established. The objective of this study was to investigate the possible toxic and teratogenic effects on the intrauterine and post-natal development of mice exposed to the dose of 15 mg kg- 1 propofol on the caudal vein fifth, tenth and fifteenth day of gestation. A significant reduction in weight gain was observed in female mice who received a 15 mg kg-1 dose of propofol on the fifth gestational day. A higher rate of embryonic loss post implantation and resorption was also observed in this group. In regards to physical development, the anesthetic increased significantly the offspring weight gain, the time in which pinna detachment occurred, and the anogenital distance of pups whose females received propofol on the fifteenth day of gestation. Based on these results, we concluded that administration of propofol in the beginning stages of gestation increases the number of abortions and promotes alterations in the physical development of pups whose mothers were anesthetized in the final stages of gestation.

A literatura mostra que o procedimento cirúrgico pode ser necessário em qualquer fase da gravidez podendo causar efeitos adversos sobre a mãe e o feto. Um dos anestésicos mais utilizados nos centros cirúrgicos é o propofol, no entanto, a sua segurança durante a gravidez não foi completamente estabelecida. O objetivo deste estudo foi investigar os possíveis efeitos tóxicos e teratogênicos no desenvolvimento intrauterino e pós-natal de camundongos expostos à dose de 15 mg kg-1 de propofol no quinto, décimo e décimo quinto dia de gestação. Observou-se uma redução significativa no ganho de peso em camundongos fêmeas que receberam uma dose de 15 mg kg-1 de propofol no quinto dia de gestação. Uma taxa maior de perda embrionária pós-implantação e reabsorção também foi observada neste grupo. Em relação ao desenvolvimento físico, o anestésico alterou significativamente o ganho de peso da prole, o tempo em que ocorreu o desprendimento da orelha e a distância anogenital dos filhotes cujas fêmeas receberam propofol no décimo quinto dia de gestação. Com base nesses resultados, concluiu-se que a administração de propofol nos estágios iniciais da gestação aumenta o número de abortos e promove alterações no desenvolvimento físico de filhotes cujas mães foram anestesiadas nos estádios finais da gestação.

Effect of alcoholic beverages on progeny and reproduction of mice

ABSTRACT Alcohol is the most commonly consumed substance in the world. The objective of this study was to evaluate the influence of alcoholic beverages on male reproduction and possible alterations in their offspring. The mice were divided into 4 groups: beer, wine, cachaça (a type of sugarcane rum), with ethanol concentrations of 1.9 g/kg, and control group treated with PBS. The treatment period was 35 days. The animals which received cachaça, demonstrated significant weight loss in the testes and epididymis. The alcoholic beverages promoted significant testosterone level and fertilization index diminution, and morphological alterations in the spermatozoa. The beer group presented decreased implantation sites and a high frequency of dominant lethal. The number of reabsorptions in the wine group was increased. The fermented beverages presented higher potential to induce visceral malformations, while the cachaça caused fetal skeletal malformations. The cachaça treated group presented a negative impact on semen quality and fertilization potential. The treatment with different alcoholic beverages, during spermatogenesis, demonstrated contrasting degrees of induction of toxic effects, interfering in a general aspect in male reproductive performance, fetal viability during intrauterine life, and birth defects. From the data, it is possible to infer that the distillated beverage caused more harmful effects to reproduction in this study.

Efeitos do metilfenidato sobre as glândulas salivares maternas de camundongos / Methylphenidate effects on maternal salivary glands of mice

Introdução: O metilfenidato (MFD) é um derivado anfetamínico estimulante do sistema nervoso central, que vem sendo cada vez mais consumido pela população mundial, incluindo as mulheres em idade fértil. Ainda não foram estabelecidos os efeitos deste medicamento nas glândulas salivares, durante a gestação. Objetivo: Identificar alterações histomorfológicas em glândulas salivares maternas expostas ao metilfenidato. Material e método: Para análise histológica, foram utilizadas 32 fêmeas de camundongos Swiss prenhes, distribuídas em um grupo controle e um grupo tratado. A administração foi realizada do quinto ao 17º dia de gestação, via injeção subcutânea; o grupo tratado recebeu 5 mg/kg de metilfenidato, enquanto o grupo controle recebeu o mesmo volume de solução salina estéril. As fêmeas foram eutanasiadas e tiveram suas glândulas salivares removidas e incluídas em parafina para análise em microscopia óptica. Para avaliar a associação entre as variáveis dos grupos, o teste de Kolmogorov-Smirnov e o teste T foram utilizados. Resultado: As glândulas parótidas do grupo tratado apresentaram alterações no raio dos ductos e na quantidade de ácinos, quando comparadas às glândulas parótidas do grupo controle. A glândula submandibular do grupo tratado foi a mais afetada: mostrou diferença estatisticamente significativa na espessura da parede dos ductos secretores, no raio dos ductos e no raio dos ácinos, quando comparada à glândula submandibular do grupo controle. A glândula sublingual não apresentou alterações significativas. Conclusão: Neste delineamento experimental, o metilfenidato apresentou-se como agente indutor de alterações morfológicas das glândulas salivares, promovendo alterações significativas nos raios de ductos e ácinos das mesmas, sendo a glândula submandibular a mais susceptível a este fármaco.

Introduction: Methylphenidate (MFD) is a stimulant amphetamine derivative of the central nervous system, which is being increasingly consumed by the world population, including women of childbearing age. It has not yet established the effects of this medicine in the salivary glands during pregnancy. Objective: Evaluate the exposure effects to the MPD in the maternal salivary glands. Material and method: For prenatal study, 32 pregnant female Swiss mice were used, divided into a control and a treated group. The treated group received 5 mg/kg of MPD via subcutaneous injection from the 5th to the 17th day and the control received sterile saline in the same volume and pregnancy period. Females were euthanized and had their salivary glands removed and embedded in paraffin for analysis in optical microscopy. To evaluate the association between the variables of the groups, the Kolmogorov-Smirnov test and and T test were used. Result: The parotid glands of the treated group showed statistically significant change within the ducts and the amount of acini when compared to the control group. The submandibular gland was the most affected, it showed a difference statistically significant in wall thickness of the secretory ducts, within the ducts and within the acini when compared to the control group. The sublingual gland showed no significant changes. Conclusion: In this experiment methylphenidate is presented as inducing agent morphological changes of the salivary glands, promoting significant changes in ducts radii and acini, submandibular gland being more susceptible to this drug.

Investigation of possible teratogenic effects in the offspring of mice exposed to methylphenidate during pregnancy.

Methylphenidate (MPH) is a central nervous system stimulant drug that increases concentration and energy level. The safety of MPH use during pregnancy is not well established. Considering the high rate of unplanned pregnancy among young women, potential for accidental exposure to MPH in early pregnancy is high. This study aimed to investigate if MPH administered during pregnancy would induce maternotoxicity, teratogenicity in mice, or both. Pregnant Swiss mice were treated with MPH (5 mg/kg, subcutaneously) or 0.9% saline (control group) from the 5th to the 17th day of pregnancy. In the MPH-treated group, a significant increase in the total number of resorptions with a consequent increase in post-implantation loss and a decrease in fetal viability were detected (all P < 0.05). A total of 91.43% of resorptions were classified as early resorptions. The group treated with MPH presented significant external (polydactyly P < 0.01), skeletal (incomplete ossification of the skull P < 0.01) and visceral (dilated ventricles P < 0.05) malformations. Behavioural effects (motor activity, memory of habituation and anxiety) were not observed in both male and female offspring evaluated at postnatal days 22, 35 and 75. The results suggest that MPH is an embryotoxic and teratogenic drug.

Maternal and fetal effects after inhalation of the herbicide flumetralin / Efeitos maternos e fetais após inalação do herbicida flumetralin

Farm workers at Brazilian tobacco plantations are frequently exposed to toxic chemicals and eventually became contaminated with these products. Flumetralin is a inhibitor of axillary bud growth on tobacco and the effects of gestational exposure should be investigated since many pesticides cross the placental barrier and cause birth defects. The aim of this study was to investigate maternal and fetal effects caused by inhalation of Flumetralin. Pregnant Swiss mice inhaled Flumetralin for 10 or 20 minutes on the seventh day of pregnancy. On the 18th day, animals were euthanized and subjected to laparotomy for removal of the uterus and embryos. The uterus was weighed and the embryos were examined. Fetuses of both treatments showed visceral changes in the uterus, kidney and liver. Skeletal abnormalities included hydrocephalus and incomplete skull ossification in both groups. In addition, the treatment of 20 minutes exposure caused anomalies in the occipital bone and the 13rd rib besides internal bleeding. There was reduction in maternal weight gain and impaired intrauterine development of the fetus. The weight of heart, liver, kidneys and testicles of fetuses were significantly decreased. Inhalation of flumetralin proved to be potentially teratogenic in both treatments, with greater damage in the group treated for 20 minutes.

Trabalhadores agrícolas nas plantações de tabaco no Brasil são frequentemente expostos a produtos químicos tóxicos e, eventualmente, são contaminados com esses produtos. O Flumetralin é um inibidor de crescimento de gemas axilares em tabaco e os efeitos de sua exposição no decorrer da gestação devem ser investigados, uma vez que muitos agrotóxicos atravessam a barreira placentária e podem causar prejuízo ao desenvolvimento embrionário. O objetivo deste estudo foi investigar os possíveis efeitos maternos e fetais da inalação de Flumetralin. Camundongos Swiss prenhes inalaram Flumetralin por 10 ou 20 minutos no sétimo dia de gestação. No 18º dia, os animais foram eutanasiados e submetidos a laparotomia para coleta do útero e dos embriões. O útero foi pesado e os embriões foram avaliados. Fetos de camundongos em ambos os tratamentos apresentaram alterações viscerais no útero, rins e fígado. Com relação a anomalias esqueléticas, ambos mostraram hidrocefalia e ossificação incompleta do crânio. Além destes, o tratamento por 20 minutos de exposição apresentou alteração no osso occipital, na 130 costela e hemorragia interna. Houve diminuição no ganho de peso materno e diminuição do desenvolvimento intrauterino dos fetos. O peso do coração, fígado, rins e testículos dos fetos foram estatisticamente diminuídos. A inalação de Flumetralina mostrou ser potencialmente teratogênica em ambos os tratamentos, com danos maiores no tratado por 20 minutos.

In vivo evaluation of the antimutagenic and antigenotoxic effects of ß-glucan extracted from Saccharomyces cerevisiae in acute treatment with multiple doses.

Ample evidence suggests that cancer is triggered by mutagenic damage and diets or supplements capable of reducing such incidences can be related to the prevention of neoplasy development or to an improvement in life quality of patients who undergo chemotherapy. This research aimed to evaluate the antimutagenic and antigenotoxic activity of ß-glucan. We set up 8 experimental groups: control (Group 1), cyclophosphamide (Group 2), Groups 3-5 to assess the effect of ß-glucan administration, and Groups 6-8 to evaluate the association between cyclophosphamide and ß-glucan. The intraperitonial concentrations of ß-glucan used were 100, 150 and 200 mg/kg. Micronucleus and comet assays showed that within the first week of treatment ß-glucan presented a damage reduction rate between 100-62.04% and 94.34-59.52% for mutagenic and genotoxic damages, respectively. This activity decreased as the treatment was extended. During the sixth week of treatment antimutagenicity rates were reduced to 59.51-39.83% and antigenotoxicity was not effective. This leads to the conclusion that the efficacy of ß-glucan in preventing DNA damage is limited when treatment is extended, and that its use as a chemotherapeutic adjuvant need to be better clarified.

Chlorophyllin in the intra-uterine development of mice exposed or not to cyclophosphamide / Clorofilina no desenvolvimento intra-uterino de camundongos expostos ou não à ciclofosfamida

Chlorophyllin, a sodium-copper salt synthesized from chlorophyll, has already proved to have anticlastogenic, antimutagenic and anticarcinogenic activity, however few are the studies in the teratogenicity area. The present study evaluated the effects of chlorophyllin in intra- uterine development of mice exposed or not to cyclophosphamide. Pregnant females were divided into 8 groups of 15 animals each, G01 - PBS (0.1 mL 10.0-1 g) orally; G02 ­ cyclophosphamide (20.0 mg kg-1) i.p.; G03, G04 and G05 - chlorophyllin at concentrations of (5.0, 10.0 and 15.0 mg kg-1) orally; G06, G07 and G08 (5.0, 10.0 and 15.0 mg kg -1) orally, of chlorophyllin, respectively, and (20.0 mg kg-1) i.p. of cyclophosphamide. In the 18th day the females were submitted to laparotomy and females and fetuses analyzed. The results showed that the chlorophyllin was not effective in protecting the reproductive parameters as well as teratogenicity. Finally, it was observed that the presence of chlorophyllin increased the frequency of some malformations when combined with cyclophosphamide. However, it was not teratogenic and not embryo lethal in this experimental design.

Clorofilina é um sal de cobre e sódio sintetizado a partir da clorofila. Provou-se ter atividade anticlastogênica, antimutagênica e anticarcinogênica. No entanto, poucos são os estudos sobre esta substância na área de teratologia. Dessa forma, o presente trabalho avaliou os efeitos da clorofilina no desenvolvimento intrauterino de camundongos expostos ou não à ciclofosfamida. Para tal, fêmeas prenhez foram divididas em oito grupos experimentais contendo 15 animais cada: G01 - PBS (0,1 mL 10.0-1 g) via oral; G02 - ciclofosfamida (20,0 mg kg-1), intraperitoneal; G03, G04 e G05 - clorofilina em concentrações de (5,0; 10,0 e 15,0 mg kg-1) via oral; G06, G07 e G08 (5,0, 10,0 e 15,0 mg kg-1) via oral, de clorofilina, respectivamente, e 20,0 mg kg-1, via intraperitoneal, de ciclofosfamida. No 18º dia de gestação, os animais foram submetidos à laparotomia e os fetos, analisados para parâmetros teratogênicos. Os resultados mostraram que a clorofilina não foi eficaz para proteger os parâmetros reprodutivos, bem como a teratogenicidade. Finalmente, foi observado que a clorofilina quando combinada com a ciclofosfamida aumentou a frequência de algumas malformações. No entanto, a clorofilina não se apresentou teratogênica e nem letal para este desenho experimental.

Exercise protects rat testis from cyclophosphamide-induced damage / O exercício físico protege o testículo de ratos de lesões teciduais induzidas por ciclofosfamida

To investigate the effect of chronic moderate exercise on male reproductive tract of Wistar rats submitted to a single dose of cyclophosphamide (CP). Animals were submitted to swimming exercise during 21 days or maintained at sedentary state. Trained (TCP) and sedentary (SCP) groups received a single dose of CP (200 mg kg-1, i.p.). Trained (TCo) and sedentary (SCo) control animals received sterile PBS. Animals were killed after one week and testis, epidydimis and seminal vesicle contend were weighted. Testis were embebbed in parafim and stained with hemotaxilin and eosin. Fifty seminiferous tubules of each animal were analyzed by Johnsen score. Mean Sertoli cells counts per tubule and Leydig cells counts per area were evaluated. CP treatment impairs body weight gain in trained and sedentary animals. Liver and seminal vesicle contend were reduced only in SCo group. SCP animals presented decreased Johnsen scores, indicating a slight toxicity over germinative cells, whereas trained (TCo and TCP) animals presented increased Johnsen scores. Training increased Sertoli cell counts and prevented their loss in TCP group. Leydig cells counts were increased in trained animals, but decreased in CP treated ones (TCP). We conclude that exercise have some protective effect on male reproductive tract submitted to a single dose of CP.

Objetivou-se investigar o efeito de exercício moderado crônico no trato reprodutivo masculino de ratos Wistar submetidos a uma dose única de ciclofosfamida (CP). Os animais foram submetidos ao exercício de natação por 21 dias ou mantidos em estado sedentário. Os grupos treinados (TCP) e sedentários (SCP) receberam uma única dose de CP (200 mg kg-1, ip). Os animais treinados (TCO) e sedentários (SCO) receberam PBS estéril. Os animais foram sacrificados após uma semana e os testículos, epidídimo e conteúdo da vesícula seminal foram pesados. As amostras foram embebidas em parafina e coradas com hematoxilina e eosina. Cinquenta túbulos seminíferos de cada animal foram analisados pelo escore Johnsen. A contagem média das células de Sertoli por túbulo e contagem das células de Leydig por área foram avaliadas. O tratamento CP prejudicou o ganho de peso corporal em animais treinados e sedentários. O fígado e o conteúdo da vesícula seminal foram reduzidos apenas no grupo SCO. Os animais SCP apresentaram menores escores de Johnsen, indicando uma toxicidade moderada sobre as células germinativas, enquanto os animais treinados (TCO e TCP) apresentaram escores de Johnsen mais altos. O treinamento aumentou a contagem de células de Sertoli e impediu a sua perda no grupo TCP. A contagem das células de Leydig foram aumentadas em animais treinados, mas reduzidas nos animais tratados com CP (TCP). Concluiu-se que o exercício tem algum efeito protetor sobre trato reprodutivo masculino de animais submetidos a uma dose única de CP.

Toxic effects of different doses of cyclophosphamide on the reproductive parameters of male mice / Os efeitos tóxicos de diferentes doses de ciclofosfamida nos parâmetros reprodutivos de camundongos machos

The cyclophosphamide is used in cancer treatment. The aim of this study was evaluating the effect of different doses of this drug on male mice reproductive parameters. The cyclophosphamide was administered in the doses 100, 150, 200 e 250 mg.kg-1, intraperitoneal route, for six weeks. As a result, it was observed a decrease in body mass and a decrease in testicles and kidney's weight, in all animals treated with cyclophosphamide. Only the groups that received the doses 100, 150 mg.kg-1 of cyclophosphamide were able to fertilize their females. There was higher incidence of post- implantation losses, reabsorptions and decrease in fetal viability in the group that received the dose of 150 mg.kg-1. It was observed a reduction in epididymis and liver's weight of the animals treated with the doses 150, 200 e 250 mg.kg-1. Abnormal spermatozoa were found in the doses 200 e 250 mg.kg-1. Based on the methodology used and results obtained, it was concluded that the cyclophosphamide was toxic, considering the decrease in animal's body mass and testicle's weight; promoted hepatotoxicity and nephrotoxic effect; influenced in the animals spermatogenesis taking them to infertility and/or subfertility; decreased fetal viability, despite it didn't cause significant malformations in the offspring.

A ciclofosfamida é utilizada no tratamento de câncer. Este estudo visa avaliar os efeitos das diferentes doses do fármaco nos parâmetros reprodutivos de camundongos machos. A ciclofosfamida foi administrada nas doses de 100, 150, 200 e 250 mg kg-1, via intraperitoneal por seis semanas. Como resultado observou-se diminuição de massa corporal, redução no peso de testículos e rins em todos os animais tratados com a ciclofosfamida. Apenas os grupos que receberam as doses de 100 e 150 mg kg-1 do quimioterápico foram capazes de fertilizar as fêmeas. Houve maior incidência de perdas pós-implantação, reabsorção e diminuição da viabilidade fetal no grupo que recebeu a dose de 150 mg kg-1. Observou-se redução nos pesos dos epidídimos e fígado dos animais tratados com as doses de 150, 200 e 250 mg kg-1. Espermatozóides anômalos foram encontrados nas doses de 200 e 250mg kg-1. Com base na metodologia empregada e nos resultados obtidos, conclui-se que a ciclofosfamida foi tóxica considerando-se a redução de massa corporal e o peso dos testículos dos animais; promoveu hepatotoxicidade e efeito nefrotóxico; influenciou na espermatogênese dos animais de forma a levá-los a um estado de infertilidade e/ou subfertilidade; diminuiu viabilidade fetal, entretanto não causou malformações significativas na prole.

Effects of the polysaccharide beta-glucan on clastogenicity and teratogenicity caused by acute exposure to cyclophosphamide in mice.

Alterations that could lead to the cancer development may also be related to an adverse development of offspring in experimental animals. Some functional foods, which contain the polysaccharide beta-glucan, have been described as being effective in the prevention of clastogenic damage. Based on that finding, the aim of the present study was to determine the efficacy of this sugar polymer in the mutagenic and teratogenic damage control. Two sets of females, pregnant and non-pregnant, were evaluated. The results indicated that beta-glucan was effective in preventing clastogenic damage in pregnant as well as non-pregnant females. In addition, pregnant females were more susceptible to mutagenic damage. However, teratogenic effects were not prevented effectively, although there was a trend toward a reduction in level of malformations. Despite beta-glucan did not prevent malformations, it increased fetal viability and reduced number of post-implantation losses and resorption, thereby enhancing reproductive performance in females.